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A r)14.7(e)5.7(la)20.5(t)7.6(e)-3.3(d ca)20.5(t)7.6(e)1.6(g)9.7(o)13.8(r)-27.3(y)1.4( o)13.8(f)1.5( tra)10.5(i)13.8(t, called )]TJ /F3 1 Tf 19.2254 0 TD -0.0082 Tc 0.0034 Tw [(th)8.2(r)10.2(e)-0.8(shold)-8.7( tr)10.2(a)7.2(i)5.3(t)-8.8(s)]TJ /F6 1 Tf 5.8267 0 TD 0.0006 Tc -0.0056 Tw [(, inc)6.1(l)12.2(udes tra)9(i)12.3(ts)]TJ -25.0522 -1.1818 TD 0.0045 Tc -0.0031 Tw [(wi)12.1(t)-6.1(h)-0.2( tw)7.9(o dis)-8.1(c)-0.2(r)13(e)-0.1(t)5.9(e)-0.1( a)-5.2(l)12(t)5.9(e)-0.1(r)-6(n)3(a)18.8(t)-5.1(i)7(v)7.9(es, w)-7(h)3.9(er)13(e t)-6.1(h)3.9(e exp)12(r)13(essio)12.1(n)-0.2( o)12.1(f)-0.2( o)12.1(n)4(e o)12.1(f)-0.2( t)-6.1(h)3.9(e tw)7.9(o a)-5.2(l)12(t)5.9(e)-0.1(r)-6(n)3(a-)]TJ T* -0.0056 Tc -0.0311 Tw [(ti)6.5(v)7.4(e)-0.6(s is det)5.4(er)-6.5(mined b)15.5(y)-0.8( w)-7.5(h)3.4(et)-6.6(her o)11.6(r)-0.7( no)10.7(t a t)-6.6(h)-0.7(r)12.5(e)-0.6(sho)6.5(ld in a)8.3(n)-0.7( underl)6.3(y)-3.7(in)7.4(g co)11.6(n)18.4(t)-5.6(in)18.4(uo)10.7(usl)6.3(y)]TJ T* -0.0011 Tc -0.0039 Tw [(distr)-6.6(i)3.4(b)10.5(u)11.3(t)5.2(e)-5.6(d tra)8.1(i)11.5(t is ex)7.2(ceeded; s)-8.7(o)11.5(me h)18.2(u)-0.9(ma)8.1(n dis)-8.7(e)-6.6(as)-8.7(es, suc)5.3(h)-0.9( as dia)7.2(b)-9.5(et)5.2(es, b)-9.5(e)3.4(ha)17.2(v)7.2(e)-0.7( in)]TJ T* -0.0049 Tc -0.0228 Tw [(t)-5.9(h)0(is wa)18(y \(F)20.1(alco)12.3(ner a)9(n)4.2(d M)17.1(a)-0.1(c)6.1(k)0(a)18(y)-0.1( 1996, Cha)19(p)11.2(t)6.1(e)0.1(r 18\).)]TJ 1.0909 -1.1818 TD -0.0044 Tc -0.0006 Tw [(V)97.4(a)7.3(r)-7.5(i)-4.6(a)6.3(b)10.6(i)-6.5(l)-1.7(i)10.6(t)-4.7(y f)7.3(o)10.6(r ei)10.6(t)-7.6(h)2.4(er mer)-7.5(i)1.5(st)-6.6(ic o)10.6(r)-1.7( met)-6.6(r)-7.5(ic)-4.6(a)-6.7(l)-1.7( t)-6.6(r)-1.7(a)7.3(i)10.6(ts is q)8.2(u)-4.7(a)7.3(n)17.4(t)-6.6(i)-1.6(f)-11.5(i)-1.6(e)-6.5(d)-1.6( b)14.5(y)-1.8( st)-7.6(a)7.3(n)2.5(d)-4.6(a)7.3(r)11.5(d)-1.6( st)-7.6(a-)]TJ -1.0909 -1.1818 TD 0.0034 Tc 0.236 Tw [(tistica)-6.3(l)-1.3( me)-7.1(asur)11.9(es suc)4.8(h)-1.3( as t)-7.2(h)2.8(e disp)-10.1(er)4.8(sio)11(n)-1.3( o)11(f)-1.3( va)-6.3(l)10.9(u)-1.4(es a)7.7(r)11.9(o)10.1(u)-1.4(nd t)-7.2(h)2.8(e me)-7.1(a)7.7(n)-1.3( \(t)-7.2(he)]TJ /F3 1 Tf T* -0.0011 Tc 0 Tw [(va)10.3(r)-14.6(i)-1.7(a)10.3(n)1.2(ce)]TJ /F6 1 Tf 3.3717 0 TD -0.0078 Tc 0.0236 Tw [(\))-12.6( or)-12.5( it)-12.5(s)-12.5( s)-20.4(q)-2.6(u)-15.5(a)-3.5(re)-12.4( ro)-21.2(ot)-12.5( \()-12.6(t)-18.4(h)-8.4(e)-12.4( )]TJ /F3 1 Tf 9.6078 0 TD 0.0005 Tc 0.0157 Tw [(s)5.8(t)5.9(a)11.9(n)2.8(da)11.9(r)14.8(d)-4.1( de)-8.1(v)-17(i)-0.1(a)18(t)4.9(io)5.8(n)]TJ /F6 1 Tf 7.4435 0 TD 0.0059 Tc 0 Tw [(s)-6.7(ee )]TJ /F1 1 Tf 2.4131 0 TD 0.0049 Tc 0.0098 Tw [(A)32.3(p)8.1(p)-11(e)5.3(ndix A2.iii)]TJ /F6 1 Tf 6.7378 0 TD 0.0047 Tc 0.0111 Tw [(\). A)]TJ -29.5739 -1.1818 TD -0.0035 Tc -0.0015 Tw [(us)-9.7(ef)-7.7(u)-6.8(l)-1.9( me)-7.6(asur)11.4(e is t)-7.7(h)2.3(e )]TJ /F3 1 Tf 8.5312 0 TD -0.0013 Tw [(c)5.3(o)2.2(eff)-9.8(i)2.3(cien)20.3(t o)9.3(f)-1.9( va)14.2(r)-10.7(i)2.3(a)20.3(t)7.2(io)8.1(n)]TJ /F6 1 Tf 8.8787 0 TD -0.0015 Tc -0.0035 Tw [(\(CV\), w)-6.6(h)0.1(ic)6.3(h is t)-5.7(h)4.3(e s)5.3(t)-5.7(a)9.1(n)4.3(da)9.1(r)13.4(d)0.2( de)-7.5(via-)]TJ -17.4099 -1.1818 TD -0.0054 Tc 0 Tw [(tio)11.8(n)-0.5( o)11.8(f)-0.5( t)-6.4(h)3.6(e tra)8.5(i)11.8(t di)6.7(vided b)15.7(y)-0.6( i)11.8(ts me)-6.3(a)8.5(n)-0.5(; t)-6.4(h)3.6(e CV r)12.7(e)-0.4(mo)15.7(v)7.6(e)-0.4(s t)-6.4(h)3.6(e s)-8.4(c)-3.4(a)-5.5(l)-0.5(e o)11.8(f)-0.5( me)-6.3(asur)12.7(emen)18.6(t,)]TJ T* 0.0043 Tc 0.1387 Tw [(a)8.6(n)3.8(d is a)18.6(p)10.8(p)11.8(r)12.8(o)15.8(x)-0.4(ima)18.6(t)5.7(el)6.6(y eq)9.5(ui)6.8(va)-5.4(len)18.7(t)-0.4( t)5.7(o)-0.3( usin)7.7(g t)-6.3(h)3.7(e na)18.6(t)9.6(u)-0.5(ra)-5.4(l loga)8.6(r)-6.2(i)11.9(t)-6.3(hm \()]TJ /F1 1 Tf 26.9644 0 TD 0.0049 Tc 0 Tw [(A)32.3(p)8.1(p)-11(e)5.3(ndix)]TJ -26.9644 -1.1818 TD 0.0015 Tc (A1.ii.c)Tj /F6 1 Tf 2.7367 0 TD 0.0021 Tc -0.0071 Tw [(\) o)12.5(f)0.2( t)-5.7(h)4.3(e tra)9.2(i)12.5(t val)12.4(u)0.1(e in)8.3(st)6.3(e)-5.6(a)0.1(d o)12.5(f)0.2( t)-5.7(h)4.3(e o)12.5(r)-5.6(iginal s)-7.6(c)-2.7(ale)6.4(.)0.3( C)-14.6(o)-8.4(ef)-9.6(f)-9.6(icien)19.3(ts o)12.5(f)0.2( va)9.2(r)-5.6(i)-2.6(a)19.2(t)-4.7(io)12.5(n)]TJ -2.7367 -1.1818 TD -0.0051 Tc -0.0204 Tw [(f)8.8(o)12.1(r ma)8.8(n)23(y)-0.3( tra)8.8(i)12.1(ts a)8.8(r)13(e o)12.1(f)-6.1(t)5.9(e)-0.1(n 10% o)12.1(r)-0.2( mo)12.1(r)13(e)-0.1( \(W)85.9(r)-6(i)-0.1(g)-6.9(h)18.8(t 1968, Cha)18.8(p)11(t)5.9(e)-0.1(r 6; Y)115.1(a)7.8(b)7(l)-0.2(o)7(k)8.9(o)16(v)-0.2( 1974\).)]TJ T* 0.0047 Tc 0.0625 Tw [(W)38(i)12.3(t)-5.9(h)0( a no)12.3(r)-5.8(m)3.2(al dis)5.1(t)-4.9(r)-5.8(i)4.2(b)11.3(u)12.1(tio)12.3(n)0(, a CV o)12.3(f)0( 10% me)-5.8(a)9(n)8.1(s t)-5.9(h)3.1(a)19(t)0( 16% o)12.3(f)0( t)-5.9(h)4.1(e p)-8.8(o)11.4(p)11.2(u)-5(la)19(tio)12.3(n)]TJ T* -0.0049 Tc -0.0225 Tw [(ha)18(v)8.1(e)0.1( val)12.2(u)-0.1(es gr)13.2(e)-5.8(a)19(t)6.1(e)0.1(r t)-5.9(h)3.1(a)9(n)0( 110% o)12.3(f)0( t)-5.9(h)4.1(e me)-5.8(a)9(n)0(, a)9(n)4.2(d 2.3% ha)18(v)8.1(e)0.1( val)12.2(u)-0.1(es o)12.3(f)0( 120% o)12.3(f)0( t)-5.9(h)4.1(e)]TJ ET 1 g 87 696 387 12 re f BT 10 0 0 10 87 700.7319 Tm 0.017 g 0 Tc 0 Tw (6)Tj /F8 1 Tf 11.0033 0 TD 0.1514 Tc -0.0003 Tw ( \012)Tj /F6 1 Tf 7.6614 0 TD -0.0005 Tc 0.0003 Tw [(| )-253.2(V)98.7(a)8.6(r)-6.2(i)-3.3(a)7.6(b)11.9(ili)11.9(t)-3.4(y a)8.6(n)3.8(d I)38.7(ts M)25.7(e)-6.2(asur)12.8(emen)18.7(t)]TJ ET /Document /MC2 BDC Q /GS3 gs BT /F6 1 Tf 9 0 0 9 199.8324 187.994 Tm /Cs8 cs 1 scn 0 Tc 0 Tw [(3)-2670.3(2)-2712.3(1)-2888.9(0)-2845(+)0(1)-2652.4(+)0(2)-2357(+)0(3)]TJ /F11 1 Tf 10 0 0 10 263.0536 173.014 Tm 0.0041 Tc -0.0041 Tw [(S)16.1(t)4.1(a)10.1(n)4.1(da)10.2(r)14.1(d)4.1( de)-8.9(via)20.1(t)4.1(io)15.1(n)]TJ ET 0 0 0 0.65 K 0 J 0 j 1 w 4 M []0 d /GS5 gs 1 i 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A s)5.4(t)6.4(o)-8.4(c)6.4(k t)-5.6(h)3.4(a)19.3(t)]TJ T* 0.0041 Tc 0.0967 Tw [(had b)-9.3(e)-5.4(en ma)8.4(in)18.5(t)-6.5(a)8.4(ined f)8.4(o)11.7(r 20 g)7.6(e)-0.5(nera)18.4(tio)11.7(n)7.5(s b)15.6(y)-0.7( b)11.7(r)12.6(o)10.8(t)-6.5(her)23.6()-0.5(sist)5.5(er ma)18.4(tin)7.5(g)-0.5( r)12.6(e)-0.5(ma)8.4(ined)]TJ T* 0.0313 Tw [(va)8.4(r)-6.4(i)-3.5(a)7.4(b)6.6(le)5.6(, b)10.7(u)11.5(t sho)15.6(w)7.5(e)-5.4(d no e)-8.3(v)-3.5(idence f)8.4(o)11.7(r pa)8.4(r)12.6(e)-0.5(n)18.5(t)-0.6(o)11.7(f)-10.4(f)-0.6(sp)11.6(r)-6.4(i)-0.5(n)7.5(g)-0.5( co)11.7(r)-6.4(r)12.6(ela)18.4(t)-5.5(io)11.7(n)7.5(s)-0.6(, a)-5.6(l)11.6(t)-6.5(h)3.5(o)10.8(u)-0.7(g)-7.3(h)]TJ T* -0.0049 Tc -0.0228 Tw [(signif)-9.8(ica)9(n)19.1(t co)12.3(r)-5.8(r)13.2(ela)19(t)-4.9(io)12.3(n)8.1(s)0( w)8.1(e)0.1(r)13.2(e)0.1( det)6.1(ec)-6.8(t)6.1(e)-4.8(d in a co)12.3(n)19.1(t)-4.9(r)13.2(o)7.2(l)6.1(,)0.1( ra)9(ndo)12.3(m)0(-b)12.3(r)13.2(e)-4.8(d st)6.1(o)-8.7(c)6.1(k.)]TJ 1.0909 -1.1818 TD 0.0039 Tc 0.2461 Tw [(Thes)-8.7(e exp)-9.6(e)-0.7(r)-6.6(i)-0.7(men)18.3(ts sho)15.4(w t)-6.7(h)2.3(a)18.2(t)-0.8(, if t)-6.7(h)3.3(e p)-9.6(o)-0.7(ssib)11.5(ili)11.5(t)-3.8(y o)11.5(f)-0.8( g)7.4(e)-0.7(netic va)8.2(r)-6.6(i)-3.7(a)18.2(t)-5.7(io)11.5(n is)]TJ -1.0909 -1.1818 TD 0.0013 Tc -0.0063 Tw [(ex)8.4(c)6.5(l)12.6(uded)6.5(, va)9.3(r)-5.4(i)-2.5(a)19.4(t)-4.5(io)12.7(n in a tra)9.3(i)12.7(t do)-8.3(es no)11.7(t allo)16.6(w a r)13.6(e)0.5(s)5.5(p)-8.4(o)12.7(n)8.5(s)-7.5(e)0.5( t)6.4(o)0.5( s)-7.5(e)4.6(lec)-6.4(t)-4.5(io)12.7(n. This r)13.6(e)0.5(s)5.5(u)-4.6(l)12.6(t)]TJ T* -0.0025 Tc -0.0025 Tw [(yields t)-6.5(h)3.5(e im)18.5(p)-9.4(o)11.8(r)-10.3(t)-6.5(a)8.4(n)18.5(t co)11.8(nc)5.6(l)11.6(u)2.5(sio)11.8(n)-0.5( t)-6.5(h)2.6(a)18.4(t)-0.6( pa)8.4(r)12.7(e)-0.5(n)18.5(ts do no)10.8(t tra)8.4(n)7.5(smi)11.7(t)-0.6( no)11.8(n)7.5(g)7.6(enetic va)8.4(r)-6.4(i)-3.4(a-)]TJ T* -0.0018 Tc -0.0032 Tw [(tio)11.4(n)-0.9( t)5.1(o)-0.8( t)-6.8(h)3.2(eir o)11.4(f)-10.7(fsp)11.3(r)-6.7(in)7.2(g. This is t)-6.8(h)3.2(e r)12.3(e)-6.7(as)-8.8(o)11.4(n)-0.9( w)-7.7(h)22.2(y b)11.4(i)-0.8(o)6.3(l)-1(ogists em)18.2(p)6.1(hasize t)-6.8(h)3.2(e distinc-)]TJ T* -0.0042 Tc -0.0008 Tw [(tio)12.1(n)-0.2( b)-8.9(e)-0.1(tw)7.9(een a)8.8(n)-0.2( indi)7(vid)12.1(u)-3.2(a)-5.2(l)25.9()95(s)-0.2( me)-6(asura)7.8(b)7(le )]TJ /F3 1 Tf 16.0018 0 TD -0.0143 Tc 0 Tw [(phe)-10.3(n)-3.3(ot)-10.3(y)-23.3(p)-6.1(e)]TJ /F6 1 Tf 4.1928 0 TD -0.0039 Tc -0.0011 Tw [(\(t)-5.8(he val)12.3(u)0(e o)12.4(f)0.1( a tra)9.1(i)12.4(t o)12.4(f)0.1( in)19.2(t)6.2(e)0.2(r-)]TJ -20.1945 -1.1818 TD 0.0047 Tc 0.118 Tw [(es)5.1(t\) a)9(n)4.2(d i)12.3(ts )]TJ /F3 1 Tf 4.9627 0 TD 0 Tw [(gen)7(o)12.2(t)0(y)-12.9(p)4.2(e)]TJ /F6 1 Tf 3.484 0 TD 0.0052 Tc 0.1175 Tw [(. I)39.6(t)0.5( im)19.6(p)7.5(l)0.5(ies t)-5.4(h)3.6(a)19.5(t)0.5( p)7.5(h)4.6(eno)11.9(t)-2.5(yp)-8.3(es a)9.5(r)13.7(e co)12.8(n)19.6(t)-4.4(r)13.7(o)7.7(lled b)16.7(y)0.4( t)-5.4(h)4.6(e jo)12.8(in)19.6(t)]TJ -8.4466 -1.1818 TD 0.0041 Tc -0.0091 Tw [(ef)-9.7(f)9.1(e)-4.8(c)-6.8(ts o)12.4(f)0( g)8.2(e)0.1(netic fac)-6.8(t)6.1(o)12.4(r)6.2(s)0( \(w)-6.7(hic)6.2(h)0( ca)9(n b)-8.7(e)0.1( tra)9(n)8.1(smi)12.3(t)10(t)6.1(e)-4.8(d t)6.1(o)0.2( t)-5.9(h)4.1(e o)12.4(f)-9.7(fs)5.1(p)12.2(r)-5.8(in)8.1(g\) a)9(n)4.2(d no)12.4(n-)]TJ T* 0.0034 Tc -0.0084 Tw [(g)8.1(e)0(netic fac)-6.8(t)6(o)12.3(r)6.1(s)-0.1( \(w)-6.8(hic)6.1(h)-0.1( a)8.9(r)13.2(e us)5(uall)7(y no)11.3(t tra)8.9(n)8(smis)5(sib)7.1(l)-0.1(e\), i)6.1(.)0.1(e)6.1(., na)18.9(t)9.9(u)-0.2(r)13.2(e)0( t)6(o)0.1(g)8.1(e)0(t)-6(h)4.1(er wi)12.2(t)-6(h)]TJ T* -0.0046 Tc -0.0004 Tw [(n)18.3(u)-0.8(r)-10.4(t)9.3(ur)12.5(e \(f)-10.5(ir)5.4(s)4.4(t)-0.8( em)18.4(p)6.3(hasized b)15.5(y)-0.8( J)20.3(o)6.5(ha)8.2(nn)7.4(s)-8.6(e)-0.6(n 1909\). I)15.5(f)-0.7( w)7.4(e)-0.6( me)-6.5(as)4.4(ur)12.5(e ma)8.2(n)22.5(y)-0.8( indi)6.4(vid)11.6(u)-3.8(als)]TJ T* -0.0026 Tc -0.0024 Tw [(wi)11.7(t)-6.4(h)-0.6( t)-6.4(h)3.6(e s)-6.5(a)8.4(me g)7.6(e)-0.5(no)10.8(typ)-9.4(e)5.6(, no)11.8(n)7.5(g)7.6(enetic ef)-10.3(f)8.5(e)-5.3(c)-7.3(ts t)-6.4(h)2.6(a)18.4(t)-0.6( incr)12.7(e)-6.3(a)2.6(s)-8.4(e)-0.5( o)11.8(r)-0.5( decr)12.7(e)-6.3(a)2.6(s)-8.4(e)-0.5( t)-6.4(h)3.6(e val)11.6(u)-0.7(es)]TJ T* 0.0021 Tc -0.0071 Tw [(o)11.7(f)-0.6( indi)6.5(vid)11.6(u)-3.7(al p)6.4(h)3.5(eno)10.7(t)-3.6(yp)-9.5(es sho)10.7(uld a)17.4(v)7.4(erag)7.5(e o)10.7(u)11.5(t, a)8.3(n)3.5(d t)-6.5(h)3.5(eir me)-6.4(a)8.3(n)-0.6( p)11.5(r)12.6(o)15.6(v)-3.6(ides a)8.3(n)-0.6( esti-)]TJ T* -0.0057 Tc -0.022 Tw [(ma)18.2(t)5.3(e)-0.7( o)11.5(f)-0.8( t)-6.7(h)3.3(e indi)6.4(vid)11.5(u)-3.8(a)-5.8(l)2.3(s)40.2()-0.8( )]TJ /F3 1 Tf 9.3394 0 TD -0.0059 Tc -0.0218 Tw [(gen)6(o)11.1(ty)-14(p)9(i)3.1(c va)10.1(l)12.3(u)3.1(e)]TJ /F6 1 Tf 5.911 0 TD 0 Tc 0 Tw (.)Tj /F1 1 Tf -9.908 -2.3636 TD 0.0495 Tc [(1.1.ii.c)-8.2(.)]TJ /F3 1 Tf 3.7109 0 TD -0.0012 Tc 0.0012 Tw [(Th)5.9(e gen)5.9(e)6(t)7.9(ic bas)8.9(i)-5.1(s o)10.1(f)-1.2( q)14.1(u)3(a)14.9(n)21(t)7.9(i)13(t)8.9(a)21(t)7.9(i)14(ve va)14.9(r)-10(i)3(a)21(b)9(i)4(l)12.2(i)13(t)-1.1(y)]TJ /F6 1 Tf -9.0534 -1.1818 TD -0.0044 Tc -0.0083 Tw [(W)12.7(h)3.6(a)19.5(t)0.5( is t)-5.4(h)4.6(e basis o)12.8(f)0.5( g)8.7(e)0.6(netic va)9.5(r)-5.3(i)-2.4(a)8.5(b)12.8(ili)12.8(t)-2.5(y in q)10.4(u)-2.5(a)9.5(n)19.6(ti)12.8(t)-5.4(a)19.5(ti)7.7(v)8.6(e)0.6( tra)9.5(i)12.8(ts? I)16.7(n)0.5( D)-5.3(a)9.5(r)-28.3(w)-2.3(in)82.6()95.7(s)0.5( time)6.7(, i)12.8(t)]TJ T* 0.0044 Tc 0.1011 Tw [(was a)-5.3(l)-0.3(most uni)6.9(v)7.8(er)5.8(s)-6.2(a)-5.3(ll)6.7(y b)-9(e)3.9(lie)-8(v)7.8(ed t)-6.2(h)2.8(a)18.7(t)-0.3( inher)-6.1(i)12(t)-6.2(a)8.7(nce w)7.8(o)12(rk)8.8(ed b)15.9(y)-0.4( t)-6.2(h)3.8(e b)6.9(l)-0.3(endin)7.8(g o)12(f)]TJ T* 0.005 Tc -0.0084 Tw [(ma)19.3(t)6.4(e)0.4(r)-5.5(i)-2.6(al f)-9.5(r)13.5(o)12.6(m)0.3( t)-5.6(h)4.4(e tw)8.4(o pa)9.3(r)13.5(e)0.4(n)19.4(ts w)-6.5(h)4.4(en o)12.6(f)-9.5(fs)5.4(p)12.5(r)-5.5(in)8.4(g a)9.3(r)13.5(e f)9.3(o)12.6(r)-5.5(m)4.5(ed)6.5(. M)26.4(e)0.4(ndel \(1866\) dis-)]TJ T* 0.0048 Tc -0.0018 Tw [(p)12.3(r)13.3(o)16.3(v)8.2(ed t)-5.8(h)0.1(is f)9.1(o)12.4(r tra)9.1(i)12.4(ts co)12.4(n)19.2(t)-4.8(r)13.3(o)7.3(lled b)16.3(y)0( sin)8.2(g)-6.6(le g)8.3(e)0.2(ne dif)-9.7(f)9.1(e)0.2(r)13.3(e)0.2(nces, a)9.1(n)4.3(d r)13.3(e)-5.7(alized t)-5.8(h)3.2(a)19.1(t)0.1( i)12.4(t)]TJ T* 0.0039 Tc -0.0089 Tw [(was als)-7.2(o)0.8( wr)13.9(o)13(n)8.8(g f)9.7(o)13(r a q)10.6(u)-2.3(a)9.7(n)19.8(ti)13(t)-5.2(a)19.7(ti)7.8(v)8.8(e)0.8( tra)9.7(i)13(t \(f)-15.2(lo)16.9(w)8.8(e)0.8(r co)7.9(lo)13(r\) t)-5.2(h)3.8(a)19.7(t)0.7( he s)5.8(t)10.7(udied)6.9(.)0.8( H)16.8(i)3.9(s ide)-5.1(a)3.8(s)]TJ T* 0.0021 Tc -0.0071 Tw [(w)7.5(e)-0.5(r)12.6(e)5.6(, ho)15.6(w)7.5(e)-8.3(v)7.5(e)-0.5(r)62.7(,)-0.5( igno)11.7(r)12.6(e)-5.4(d)5.6(.)-0.5( The o)4.7(b)-0.5(s)-8.5(e)-0.5(r)-29.4(v)-0.6(a)18.4(t)-5.5(io)11.7(n t)-6.5(h)2.5(a)18.4(t)-0.6( t)-6.5(h)3.5(e F1 h)22.6(y)-12.7(b)11.7(r)-6.4(id p)11.6(r)12.6(og)7.6(en)22.6(y o)11.7(f)-0.6( a cr)12.6(oss)]TJ T* 0.0055 Tc 0.0773 Tw [(b)-7.9(e)0.9(tw)8.9(een tw)8.9(o in)10.8(b)13.1(r)14(ed lines a)9.8(r)14(e o)13.1(f)-5.1(t)6.9(e)0.9(n in)19.9(t)6.9(e)0.9(r)-5(m)5(edia)19.8(t)6.9(e)0.9( in me)-5(a)9.8(n)0.8( val)13(u)0.7(e b)-7.9(e)0.9(tw)8.9(een t)-5.1(h)4.9(e)]TJ T* 0.0043 Tc 0.2022 Tw [(me)-6.2(a)8.6(n)7.7(s o)11.9(f)-0.4( t)-6.3(h)3.7(e tw)7.7(o pa)8.6(r)12.8(e)-0.3(n)18.7(t)-6.3(a)-5.4(l)-0.4( lines s)-8.3(e)-5.2(emed t)5.7(o)-0.3( su)11.7(p)10.8(p)-9.2(o)11.9(r)-10.1(t b)6.8(l)-0.4(endin)7.7(g inher)-6.2(i)11.9(t)-6.3(a)8.6(nce)5.8(.)]TJ T* -0.0021 Tc -0.0029 Tw [(M)26.1(e)0.1(ndel)26.1()95.2(s)-0.1( q)9.9(u)-3.1(a)9(n)19.1(ti)12.3(t)-5.9(a)19(ti)7.1(v)8.1(e)0.1( a)19(p)11.2(p)12.2(r)13.2(oac)6.1(h)-0.1(, inc)6.1(l)12.2(udin)8.1(g t)-5.9(h)4.1(e st)10(ud)7.1(y o)12.3(f)0( la)19(t)6.1(e)0.1(r g)8.2(e)0.1(nera)19(tio)12.3(n)8.1(s as w)8.1(e)4.2(ll)]TJ T* -0.005 Tc -0.0138 Tw [(as t)-6(h)4(e F1, est)-6(a)7.9(b)7.1(l)-0.1(ished t)-6(h)3(a)18.9(t)-0.1( 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F)16.8(o)10(r no)13.9(w)70.8(,)-2.2( we ne)-7.1(e)-7.1(d)]TJ -23.8092 -1.1818 TD -0.0054 Tc -0.0108 Tw [(o)11.8(n)-5.4(l)6.5(y)-0.6( no)10.9(t)5.6(e)-0.4( t)-6.4(h)2.6(a)18.5(t)-0.5( estima)18.5(t)5.6(e)-0.4(s o)11.8(f)-0.5( t)-6.4(h)3.6(e co)11.8(r)-6.3(r)12.7(ela)18.5(t)-5.4(io)11.8(n)7.6(s)-0.5( \(s)-8.4(ee )]TJ /F1 1 Tf 18.6273 0 TD -0.0051 Tc [(A)32.3(p)8.1(p)-11(e)5.3(ndix A2.iv)]TJ /F6 1 Tf 6.4472 0 TD -0.0038 Tc -0.0124 Tw [(\) b)-7.6(e)1.2(tw)9.2(een c)7.2(l)1.1(os)-6.8(e)]TJ -25.0745 -1.1818 TD -0.0046 Tc -0.0118 Tw [(r)13.5(e)4.5(la)19.3(ti)7.5(v)8.4(e)0.4(s, suc)6.4(h)0.3( as pa)9.3(r)13.5(e)0.4(n)19.4(ts a)9.3(n)4.5(d o)12.6(f)-9.5(fsp)12.5(r)-5.5(in)8.4(g, o)12.6(r)0.3( sib)7.5(l)0.3(in)8.4(gs, ca)9.3(n b)-8.4(e)0.4( us)-7.6(ed t)6.4(o)0.4( inf)9.3(e)0.4(r t)-5.6(h)4.4(e p)12.5(r)13.5(o-)]TJ T* 0.005 Tc 0.0331 Tw [(p)-8.5(o)12.6(r)-9.4(t)-4.6(io)12.6(n o)12.6(f)0.3( t)-5.6(h)4.4(e va)9.3(r)-5.5(i)-2.6(a)9.3(n)4.5(ce in a tra)9.3(i)12.6(t in a s)-7.6(e)0.4(xua)-4.7(l)-4.6(l)7.3(y)0.2( r)13.5(e)0.4(p)12.5(r)13.5(o)-8.4(d)12.6(ucin)8.4(g p)-8.5(o)11.7(p)11.5(u)-4.7(la)19.3(tio)12.6(n)0.3( t)-5.6(h)3.4(a)19.3(t)0.3( is)]TJ T* 0.0073 Tc 0.0323 Tw [(ca)21.6(u)5.7(s)-5.3(ed b)18.8(y)2.5( )]TJ /F3 1 Tf 4.2281 0 TD 0.0029 Tc 0.0374 Tw [(a)5.2(d)2.5(d)11.5(i)12.3(t)7.3(i)13.3(ve gen)5.2(e)5.3(t)7.3(ic)]TJ /F6 1 Tf 6.4317 0 TD 0.0048 Tc 0.0348 Tw [(ef)-9.7(f)9.1(e)-4.7(c)-6.7(ts. 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I)16.3(n)0.1( o)11.5(t)-5.8(her w)8.2(o)12.4(r)13.3(d)3.3(s, t)-5.8(h)4.2(e addi)12.4(ti)7.3(v)8.2(e)0.2( g)8.3(e)0.2(netic val)12.3(u)0(e is t)-5.8(h)4.2(e co)12.4(m)19.2(p)-8.7(o)12.4(n)4.3(en)19.2(t)]TJ T* 0.0042 Tc 0.05 Tw [(o)11.8(f)-0.5( t)-6.4(h)3.6(e g)7.7(e)-0.4(no)10.9(typ)-9.3(e)-0.4( t)-6.4(h)2.6(a)18.5(t)-0.5( is tra)8.5(n)7.6(smis)4.6(s)-0.5(ib)6.7(le t)5.6(o)-0.4( t)-6.4(h)3.6(e o)11.8(f)-10.3(fs)4.6(p)11.7(r)-6.3(in)7.6(g \(in o)11.8(r)7.6(ga)8.5(nism)7.6(s in w)-7.3(h)-0.5(ic)5.6(h)]TJ T* 0.0006 Tc -0.0056 Tw [(mo)10.9(t)-6.3(h)3.7(er)5.7(s p)11.7(r)12.8(o)15.8(v)-3.4(isio)11.9(n t)-6.3(h)3.7(eir y)7.5(o)10.9(un)7.6(g, i)11.8(t)-0.5( is im)18.7(p)-9.3(o)11.9(r)-10.2(t)-6.3(a)8.5(n)18.6(t t)5.6(o)-0.3( ex)7.6(c)5.7(l)11.7(ude no)11.9(n)7.6(g)7.7(enetic ma)18.5(t)5.6(e)-0.3(r)-6.3(n)2.8(al)]TJ T* -0.0053 Tc 0 Tw [(inf)-16.3(l)11.8(uences\).)]TJ 1.0909 -1.1818 TD 0.0033 Tc -0.0083 Tw [(Estima)19.3(t)6.4(e)0.4(s o)12.7(f)0.3( indi)7.5(vid)12.6(u)-2.7(als)41.3()0.3( addi)12.6(ti)7.5(v)8.4(e)0.4( g)8.5(e)0.4(netic val)12.5(u)0.2(es a)9.3(r)13.6(e us)-7.5(ef)-5.5(u)-4.7(l)0.3( in a)9.3(nimal b)12.6(r)13.6(eed-)]TJ -1.0909 -1.1818 TD -0.0051 Tc -0.0015 Tw [(in)7.9(g, w)-7(h)3.9(er)13(e a)8.8(r)-9.9(tif)-10(i)-0.1(cia)-5.2(l)-0.2( in)7.9(s)-8.1(e)-0.1(mina)18.8(tio)12.1(n)-0.2( ca)8.8(n b)-8.9(e)-0.1( us)-8.1(ed t)5.9(o)-0.1( p)12(r)13(o)-8.9(d)12.1(uce ma)8.8(n)23(y)-0.3( p)12(r)13(og)8(en)23(y f)-10(r)13(o)12.1(m)-0.2( a)]TJ T* -0.002 Tc -0.003 Tw [(sin)7.8(g)-7(le male \(B)7.8(r)13(o)11.1(t)-6.2(h)3.8(er)5.9(s)4.8(t)5.8(o)12.1(n)3.9(e a)8.7(n)3.9(d G)-8(o)-8.9(dda)8.7(r)13(d 2005\). I)15.9(n)-0.2( o)11.1(t)-6.2(her si)12(t)9.7(u)-3.3(a)18.7(t)-5.2(io)12.1(n)7.8(s)-0.3(, w)7.9(e)-0.2( ca)8.7(n o)12.1(n)-5.1(l)6.8(y)]TJ T* 0.0044 Tc -0.0087 Tw [(me)-6.1(asur)12.9(e t)-6.2(h)3.8(e p)11.9(r)12.9(o)11.1(p)-9.1(o)12(r)-10(tio)12(n)-0.3( o)12(f)-0.3( t)-6.2(h)3.8(e t)5.8(o)11.1(t)-6.2(a)-5.3(l p)6.7(h)3.8(eno)11.1(t)-3.3(yp)11.9(ic va)8.7(r)-6.1(i)-3.1(a)8.7(n)3.9(ce in a tra)8.7(i)12(t co)12(n)18.8(t)-5.2(r)-6.1(i)3.9(b)11(u)11.8(t)5.8(e)-5.1(d)]TJ T* -0.0047 Tc -0.006 Tw [(b)16.4(y)0.1( t)-5.7(h)4.3(e va)9.2(r)-5.6(i)-2.7(a)9.2(n)4.4(ce in addi)12.5(ti)7.4(v)8.3(e)0.3( g)8.4(e)0.3(netic va)-4.8(l)12.4(u)0.1(es \(t)-5.7(he )]TJ /F3 1 Tf 18.064 0 TD -0.0145 Tc 0 Tw [(he)-9.6(r)-18.5(i)4.5(ta)12.5(bilit)-9.6(y)]TJ /F6 1 Tf 4.2316 0 TD -0.0055 Tc -0.0052 Tw [(\). 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The diagra)8.9(m sho)16.1(ws a wild-ca)18.9(u)-0.2(g)-6.8(h)18.9(t ma)-5.1(le a)18.9(t)-0.1( t)-6(h)4(e t)6(o)11.3(p r)-5.9(i)0(g)-6.8(h)18.9(t \(w)-6.9(hos)-8(e)0( tw)8(o)]TJ T* [(c)6(h)-0.1(r)13.1(o)12.2(mos)-8(o)12.2(mes a)8.9(r)13.1(e deno)11.3(t)6(ed b)16.1(y)-0.2( +\). The ba)-5.1(la)8.9(ncer c)6(h)-0.1(r)13.1(o)12.2(mos)-8(o)12.2(me ca)8.9(r)-5.9(r)-5.9(ies s)-8(e)-7.8(v)8(e)0(ra)-5.1(l in)23.1(v)8(e)0(r)6.1(s)-0.1(io)12.2(n)8(s)-0.1( \()]TJ /F1 1 Tf 34.3333 0 TD 0.0073 Tc [(Sec)6.6(t)17.6(i)6.5(o)22.4(n)]TJ -34.3333 -1.2222 TD -0.0051 Tc (1.1.i)Tj /F6 1 Tf 1.7777 0 TD -0.0059 Tc 0.0009 Tw [(\) t)-6.9(h)2.1(a)18(t)-1( su)11.1(p)10.2(p)11.2(r)12.2(e)-0.9(ss cr)12.2(ossin)7.1(g)-0.9( o)15.2(v)7.1(er wi)11.3(t)-6.9(h)-1( t)-6.9(h)3.1(e no)11.3(r)-6.8(m)2.2(a)-6(l)-1( s)-8.9(e)-5.8(co)11.3(nd c)5.1(h)-1(r)12.2(o)11.3(mos)-8.9(o)11.3(me in het)5.1(e)-0.9(r)12.2(o)5.2(zyg)7.2(o)10.4(us f)8(e)-0.9(ma)-6(les)]TJ -1.7777 -1.2222 TD 0 Tc 0 Tw (\()Tj /F3 1 Tf 0.3412 0 TD -0.0011 Tc [(Dr)22.7(o)9.8(s)0.8(o)12.7(p)13.8(h)20.8(i)8.8(l)8(a)]TJ /F6 1 Tf 4.4698 0 TD -0.0055 Tc 0.0005 Tw [(ma)-5.6(les ha)17.4(v)7.5(e)-0.5( no cr)12.6(ossin)7.5(g)-0.5( o)15.6(v)7.5(er\). The ba)-5.6(la)8.4(ncer a)-5.6(l)2.5(s)-8.5(o)-0.5( ca)8.4(r)-6.4(r)-6.4(ies a do)11.7(mina)8.4(n)18.5(t)-0.6( ma)8.4(rk)8.5(er g)7.6(e)-0.5(ne \()]TJ /F3 1 Tf 32.0362 0 TD -0.0402 Tc 0 Tw (Cy)Tj /F6 1 Tf -36.8471 -1.2222 TD -0.005 Tc [(in t)-6(h)-0.1(is exa)8.9(m)19(p)7(l)-0.1(e)6.1(,)0( w)-6.9(h)-0.1(ic)6(h gi)7.1(v)8(e)0(s t)-6(h)4(e f)-16(l)-0.1(ies c)-6.9(u)-0.2(rled win)8(g)0(s\), det)6(ec)-6.9(t)-6(a)7.9(b)7.1(l)-0.1(e in ca)8.9(r)-5.9(r)-5.9(ier f)-16(l)-0.1(ies. The ma)8.9(rk)9(er is)]TJ T* -0.0054 Tc 0.0004 Tw [(ho)11.8(mo)5.7(zyg)7.7(o)10.9(us let)-6.4(h)2.6(a)-5.5(l)5.6(, a)8.5(n)3.7(d t)-6.4(h)3.6(e ba)-5.5(la)8.5(ncer is k)8.6(e)-0.4(p)10.7(t)-0.5( in a st)5.6(o)-9.2(c)5.6(k \(t)-6.4(he lef)-6.4(t)-0.5(-ha)8.5(n)3.7(d g)7.7(e)-0.4(no)10.9(typ)-9.3(e)-0.4( in t)-6.4(h)3.6(e t)5.6(o)10.9(p tw)7.6(o)]TJ T* -0.0056 Tc 0.0006 Tw [(g)7.5(e)-0.6(nera)18.3(tio)11.6(n)7.4(s\) w)-7.5(h)3.4(os)-8.6(e o)10.7(t)-6.6(her s)-8.6(e)-5.5(co)11.6(nd c)5.4(h)-0.7(r)12.5(o)11.6(mos)-8.6(o)11.6(me ca)8.3(r)-6.5(r)-6.5(ies a)8.3(n)3.5(o)10.7(t)-6.6(her do)11.6(mina)8.3(n)18.4(t)-0.7( ma)8.3(rk)8.4(er)62.6(, )]TJ /F3 1 Tf 32.1035 0 TD -0.008 Tc 0 Tw (Pm)Tj /F6 1 Tf 1.5501 0 TD -0.0037 Tc [(\(gi)8.4(v)-1.7(in)9.3(g)]TJ -33.6536 -1.2222 TD -0.0054 Tc 0.0004 Tw [(da)8.5(rk r)12.7(e)-5.3(d e)-8.2(y)7.5(es, in)7.6(st)5.6(e)-6.3(a)-0.6(d o)11.8(f)-0.5( t)-6.4(h)3.6(e usua)-5.5(l b)11.8(r)-6.3(ig)-7.2(h)18.5(t)-0.5( r)12.7(e)-5.3(d\), w)-7.3(h)-0.5(ic)5.6(h is a)-5.5(l)2.6(s)-8.4(o)-0.4( let)-6.4(h)2.6(a)-5.5(l)-0.5( w)-7.3(h)3.6(en ho)11.8(mo)5.7(zyg)7.7(o)10.9(us. 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The)-7.3(y)0.3( st)10.4(udied ma)9.4(n)23.6(y)0.3( dif)-9.4(f)9.4(e)0.5(r)13.6(e)0.5(n)19.5(t)0.4( s)-7.5(o)7.6(l)12.6(u)4.4(b)7.6(l)0.4(e p)12.6(r)13.6(o)11.8(t)6.5(ein)8.5(s co)12.7(n)19.5(t)-4.5(r)13.6(o)7.6(lled)]TJ -7.8189 -1.1818 TD 0.0032 Tc -0.0082 Tw [(b)15.5(y)-0.8( indep)-9.5(enden)18.4(t g)7.5(e)-0.6(nes, most)-6.6(l)6.3(y)-0.8( enzymes wi)11.6(t)-6.6(h)-0.7( w)7.4(e)3.5(ll-under)5.4(st)5.4(o)-9.4(o)-9.4(d)-0.6( met)-6.6(a)7.3(b)-9.4(o)6.5(lic r)12.5(o)6.5(les.)]TJ T* 0.0028 Tc -0.0078 Tw [(The p)12(r)13(o)11.2(t)5.9(ein)7.9(s w)7.9(e)-0.1(r)13(e)-0.1( c)6(h)3.9(os)-8.1(en p)11(u)-0.3(r)13(e)4(l)6.9(y)-0.3( b)-8.9(e)-5(ca)18.8(us)-8.1(e t)-6.1(h)3.9(e)-7.9(y)-0.3( co)11.2(u)-5.2(l)-0.2(d b)-8.9(e)-0.1( st)9.8(udied e)-6(a)2.9(sil)6.9(y)72.7(, wi)12.1(t)-6.1(h)-0.2( no)]TJ T* 0.0047 Tc 0.083 Tw [(b)12.3(i)-2.9(as as t)6.1(o)0.1( t)-5.9(h)4.1(eir le)-7.7(v)8.1(e)4.2(l o)12.3(f)0( va)9(r)-5.8(i)-2.9(a)8(b)12.3(ili)12.3(t)-3(y)72.9(.)0.1( Enzyme lo)-8.7(ci det)6.1(ec)-6.8(t)6.1(e)-4.8(d b)16.2(y)-0.1( t)-5.9(h)0(is met)-5.9(h)4.1(o)-8.7(d)0.1( a)9(r)13.2(e)]TJ T* -0.003 Tc -0.0247 Tw [(kn)6.1(o)18.1(w)-0.9(n a)5(s)1.9( )]TJ /F3 1 Tf 3.9386 0 TD -0.014 Tc 0 Tw [(al)-3.9(l)-4.9(o)5(z)-9.2(y)-22.1(me)]TJ /F6 1 Tf 3.6366 0 TD -0.0049 Tc [(lo)-8.7(ci)6.2(.)]TJ -6.4842 -1.1818 TD 0.004 Tc 0.062 Tw [(This met)-6.6(h)3.4(o)-9.4(d)-0.6( is o)10.7(u)11.4(t)-6.6(l)-0.7(ined in )]TJ /F1 1 Tf 11.2752 0 TD -0.0032 Tc 0.0659 Tw [(Fi)-8.1(g)-11.1(u)-8.1(re)-8( 1)-8.2(.)-8.1(6)]TJ /F6 1 Tf 4.3018 0 TD 0.0047 Tc 0.0613 Tw [(. P)32.1(o)7.2(l)7(y)-0.1(p)-8.8(e)0.1(p)11.2(t)-4.9(ides enco)-8.7(ded b)16.2(y)-0.1( dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(n)19.1(t)]TJ -16.6679 -1.1818 TD 0.0042 Tc 0.0725 Tw [(a)-5.5(l)-5.4(leles a)18.5(t)-0.5( a lo)-9.2(c)-7.3(u)2.6(s ma)17.5(y dif)-10.3(f)8.5(e)-0.4(r b)15.7(y)-0.6( o)11.8(n)3.7(e o)11.8(r)-0.5( a f)8.5(e)-8.2(w a)8.5(m)-0.5(ino acids in t)-6.4(h)3.6(eir s)-8.4(e)-5.3(q)9.4(u)-0.6(ences.)]TJ T* 0.0047 Tc 0.1087 Tw [(S)-13.9(o)12.3(me a)9(m)0(ino acid dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(nces in)23.2(v)8.1(o)7.2(l)7(v)8.1(e r)13.2(e)0.1(sid)12.3(u)-0.1(es w)-6.8(h)4.1(os)-7.9(e elec)-6.8(tr)-5.8(ic c)6.1(h)3.1(a)9(r)8.1(g)8.2(e)0.1(s dif)-9.8(f)9(e)0.1(r)63.3(,)]TJ T* 0.0869 Tw [(ca)19(usin)8.1(g dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(n)19.1(t)0( mo)5.3(b)12.3(i)-4.8(li)12.3(ties in g)8.2(e)4.2(ls exp)-8.8(o)0.1(s)-7.9(e)-4.8(d t)6.1(o)0.1( elec)-6.8(tr)-5.8(ic c)-6.8(u)-0.1(r)-5.8(r)13.2(en)19.1(ts, r)13.2(e)0.1(su)-5(l)12.2(t)-4.9(in)8.1(g in)]TJ T* -0.0041 Tc -0.0009 Tw [(det)6(e)-4.8(c)-6.8(t)-5.9(a)8(b)7.1(le dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(nces in ba)8.9(nd p)-8.9(o)0.1(si)12.2(tio)12.3(n)8(s. I)16.2(n)0( t)-5.9(h)4.1(e exa)8.9(m)19.1(p)7(l)-0.1(e)6.2(,)0.1( tw)8.1(o typ)-8.9(e)0.1(s, fast \()]TJ /F3 1 Tf 28.5115 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.5229 0 TD -0.004 Tc -0.001 Tw [(\) a)9(n)4.2(d)]TJ -29.0345 -1.1818 TD -0.0052 Tc 0.0002 Tw [(slo)14.4(w)-1.8( \()]TJ /F3 1 Tf 2.3461 0 TD 0 Tc 0 Tw (S)Tj /F6 1 Tf 0.4646 0 TD -0.0036 Tc -0.0014 Tw [(\), a)8.7(r)12.9(e distin)7.8(guisha)7.7(b)6.9(l)-0.3(e)5.9(.)-0.2( S)13.9(u)-0.4(c)5.9(h)-0.3( va)8.7(r)-6.1(i)-3.1(a)8.7(n)18.8(ts a)8.7(r)12.9(e g)7.9(e)-0.2(nerall)6.8(y inher)-6.1(i)12(t)5.8(e)-5.1(d as alleles a)18.7(t)-0.3( a)]TJ -2.8106 -1.1818 TD -0.0031 Tc -0.0019 Tw [(sin)7.3(g)-7.5(le lo)-9.4(c)-7.5(u)2.3(s. I)15.4(n)-0.7( t)-6.6(h)3.4(e sim)18.3(p)6.3(les)4.3(t)-0.8( si)11.5(t)9.2(u)-3.8(a)18.2(t)-5.7(io)11.6(n o)11.6(f)-0.7( a mo)11.6(no)11.6(mer)-6.6(ic enzyme \(lo)15.5(w)7.4(er lef)-6.6(t-ha)8.2(n)3.4(d)]TJ T* -0.0029 Tc -0.0021 Tw [(diagra)9.1(m in )]TJ /F1 1 Tf 4.5569 0 TD -0.0113 Tc 0.0061 Tw [(Fi)-8.1(g)-11.1(u)-8.2(re)-8( 1)-8.2(.)-8.1(6)]TJ /F6 1 Tf 4.1612 0 TD -0.0037 Tc -0.0013 Tw [(\), fast indi)6.5(vid)11.6(u)-3.7(als a)8.3(r)12.6(e ho)11.7(mo)5.6(zyg)7.5(o)10.7(t)5.4(es f)8.4(o)11.7(r tw)7.5(o )]TJ /F3 1 Tf 16.9954 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.7459 0 TD -0.0011 Tc -0.0039 Tw [(alle)6.2(l)1.9(es,)2.1( s)6.1(l)1.9(o)18.2(w)]TJ -26.4594 -1.1818 TD 0.0045 Tc 0.002 Tw [(indi)7(vid)12.1(u)-3.2(als a)8.8(r)13(e ho)12.1(mo)6(zyg)8(o)11.2(us f)8.8(o)12.1(r tw)7.9(o slo)16(w)-0.1( alleles \()]TJ /F3 1 Tf 19.7791 0 TD 0 Tc 0 Tw (S)Tj /F6 1 Tf 0.4725 0 TD 0.0054 Tc 0.0011 Tw [(\), a)9.7(n)4.9(d indi)7.9(vid)13(u)-2.3(a)-4.3(l)3.8(s wi)13(t)-5.2(h)0.7( tw)8.8(o)]TJ -20.2516 -1.1818 TD 0.0044 Tc 0.2717 Tw [(ba)8.7(nds a)8.7(r)12.9(e het)5.8(e)-0.2(r)12.9(o)5.9(zyg)7.9(o)11.1(us, )]TJ /F3 1 Tf 10.6989 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.5316 0 TD (/)Tj /F3 1 Tf 0.3356 0 TD (S)Tj /F6 1 Tf 0.4725 0 TD 0.0046 Tc 0.2715 Tw [(. W)12.1(h)4(en t)-6(h)4(e tw)8(o a)-5.1(l)-5(leles in het)6(e)0(r)13.1(o)6.1(zyg)8.1(o)11.3(t)6(e)0(s a)8.9(r)13.1(e)]TJ -12.0387 -1.1818 TD 0.0052 Tc 0.0995 Tw [(det)6.6(ec)-6.3(t)-5.4(a)8.5(b)7.7(l)0.5(e)6.7(,)0.6( t)-5.4(h)4.6(e va)9.5(r)-5.3(i)-2.4(a)9.5(n)19.6(ts a)9.5(r)13.7(e s)-5.4(a)9.5(id t)6.6(o)0.6( b)-8.2(e)0.6( )]TJ /F3 1 Tf 15.7291 0 TD -0.0019 Tc 0 Tw [(codom)10.6(i)6.6(na)9.5(n)15.6(t)]TJ /F6 1 Tf 4.6969 0 TD 0.0035 Tc 0.1012 Tw [(, as is usu)-4.2(a)-6.2(l)-6.1(l)5.8(y t)-7.1(h)2.9(e c)-4.1(a)1.9(s)-9.1(e)-1.1( f)7.8(o)11.1(r)]TJ -20.426 -1.1818 TD -0.0047 Tc -0.0202 Tw [(allo)6.4(zyme va)9.2(r)-5.6(i)-2.7(a)9.2(n)19.3(ts. S)-13.7(o)12.5(metimes m)19.3(u)-4.8(l)12.4(t)-4.7(i)12.5(p)7.3(le dif)-9.6(f)9.2(e)0.3(r)13.4(e)0.3(n)19.3(t)0.2( allelic f)9.2(o)12.5(r)-5.6(m)8.3(s o)12.5(f)0.2( t)-5.7(h)4.3(e p)-8.6(o)7.4(l)7.2(y)0.1(p)-8.6(e)0.3(p)11.4(t)-4.7(ide)]TJ T* 0.0042 Tc 0.0069 Tw [(a)8.5(r)12.7(e co)11.8(n)18.6(t)-5.4(r)12.7(o)6.7(lled b)15.7(y)-0.6( t)-6.4(h)3.6(e s)-6.4(a)8.5(me g)7.7(e)-0.4(ne)5.7(, o)11.8(r)-0.5( mo)11.8(r)12.7(e)-0.4( t)-6.4(h)2.6(a)8.5(n)-0.5( o)11.8(n)3.7(e p)-9.3(o)6.7(l)6.5(y)-0.6(p)-9.3(e)-0.4(p)10.7(t)-5.4(ide co)11.8(n)18.6(t)-5.4(r)-6.3(i)3.7(b)10.8(u)11.6(t)5.6(e)-0.4(s t)5.6(o)]TJ ET 1 g 114 696 387 12 re f BT 10 0 0 10 203.5202 700.7319 Tm 0.017 g 0.1439 Tc 0.2531 Tw (1.2 | )Tj /F8 1 Tf 3.2746 0 TD 0.151 Tc 0.0001 Tw [( )-12.1( )88.9(\015\015\015)-15.1()]TJ /F6 1 Tf 25.5134 0 TD 0 Tc 0 Tw (15)Tj ET /Document /MC6 BDC Q q 1 i 439.437 778.461 -400.527 -261.326 re 38.91 778.461 m W n 114 684 342 -167.022 re 501 700.732 m W* n 0 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n /GS3 gs BT /F15 1 Tf 10 0 0 9.994 209.067 585.4929 Tm /Cs8 cs 1 scn 0 Tc 0 Tw [(Enzyme b)-5.9(a)8(ndin)8(g p)-6(a)18(t)11(t)7(ern)7(s)0( \(o)11(ne lo)-9.9(c)-7(u)3(s\))]TJ /F12 1 Tf 9 0 0 8.9946 176.856 530.366 Tm -0.0013 Tc 0.0012 Tw [(M)24.7(o)10.7(no)10.7(mer)-7.3(ic enzyme)]TJ -1.2353 -1.1111 TD -0.0005 Tc 0.0004 Tw [(One p)-9.5(o)6.5(l)6.5(y)-0.5(p)-9.5(e)-0.5(p)10.5(t)-5.5(ide mo)6.5(lec)-7.5(u)-5.4(le)]TJ 17.6471 1.1111 TD -0.0007 Tc 0.0007 Tw [(Dimer)-6.7(ic enzyme)]TJ -2.1929 -1.1111 TD -0.0002 Tc 0.0002 Tw [(T)72.9(w)7.7(o p)-9.2(o)6.9(l)6.8(y)-0.3(p)-9.2(e)-0.1(p)10.8(t)-5.2(ide mo)6.8(lec)-7.2(u)-5.1(les)]TJ -19.5936 17.0418 TD 0 Tc 0 Tw [(S)14(u)4(bstra)19(t)6(e)]TJ -0.0623 -2.486 TD -0.0011 Tc [(D)-7.1(e)2.9(h)21.9(y)6.9(dr)11.9(og)6.9(enas)-9(e)]TJ 0.0779 -2.074 TD 0.001 Tc [(O)8(x)1.1(idized)]TJ 0.464 -1.1111 TD 0 Tc [(p)12(r)13(o)-9(d)12(uc)-7(t)]TJ 9.3143 5.6711 TD -0.038 Tc [(NA)-38(D)]TJ -0.0494 -5.2451 TD [(NA)-38(D)-29(H)]TJ 9.748 5.5783 TD 0 Tc [(MT)-27(T)]TJ -0.899 -1.1111 TD 0.0017 Tc [(\(r)14.7(ed)13.8(uced\))]TJ 0.6767 -3.7821 TD 0 Tc [(MT)-27(T)]TJ -0.993 -1.1111 TD 0.0005 Tc [(\(o)16.6(xidized\))]TJ 9.8849 5.6711 TD 0.0003 Tc -0.0003 Tw [(PMS \(o)16.3(xidized\))]TJ 0.4494 -5.2452 TD 0.0014 Tc -0.0014 Tw [(PMS \(r)14.4(ed)13.5(uced)7.4(,)]TJ 1.9485 -1.1111 TD 0 Tc 0 Tw [(b)7(l)12(ue\))]TJ ET /Cs8 CS 1 SCN 0 J 0 j 0.5 w 4 M []0 d /GS4 gs 209.801 631.584 m 196.298 635.691 187.054 644.054 187.054 653.701 c 187.054 663.355 196.306 671.721 209.817 675.826 c S 209.313 631.733 m 208.789 633.774 l 208.86 633.796 l 211.33 631.824 l 212.244 631.312 213.158 630.8 214.072 630.285 c 213.027 630.368 211.982 630.45 210.937 630.533 c 207.787 630.272 l 207.738 630.32 l 209.313 631.733 l f 379.801 631.584 m 366.299 635.691 357.055 644.054 357.055 653.701 c 357.055 663.355 366.306 671.721 379.818 675.826 c S 379.314 631.733 m 378.791 633.774 l 378.861 633.796 l 381.332 631.824 l 382.244 631.312 383.158 630.8 384.072 630.285 c 383.027 630.368 381.982 630.45 380.937 630.533 c 377.789 630.272 l 377.738 630.32 l 379.314 631.733 l f 245.321 674.597 m 258.995 670.527 268.385 662.108 268.385 652.384 c 268.385 642.665 259.002 634.248 245.336 630.176 c S 245.81 674.453 m 246.345 672.415 l 246.275 672.393 l 243.793 674.349 l 242.876 674.856 241.959 675.364 241.043 675.872 c 242.088 675.795 243.133 675.719 244.179 675.643 c 247.327 675.922 l 247.377 675.876 l 245.81 674.453 l f 292.132 630.272 m 278.629 634.379 269.385 642.741 269.385 652.389 c 269.385 662.043 278.638 670.409 292.148 674.513 c S 291.66 674.365 m 290.089 675.77 l 290.135 675.826 l 293.285 675.564 l 294.33 675.647 295.375 675.729 296.419 675.811 c 295.506 675.298 294.592 674.785 293.678 674.273 c 291.207 672.303 l 291.139 672.315 l 291.66 674.365 l f 333.658 675.922 m 347.334 671.85 356.723 663.432 356.723 653.707 c 356.723 643.987 347.34 635.572 333.674 631.499 c 163.658 675.922 m 177.333 671.85 186.722 663.432 186.722 653.707 c 186.722 643.987 177.339 635.572 163.673 631.499 c S 334.162 631.645 m 335.726 630.233 l 335.68 630.176 l 332.531 630.455 l 331.486 630.378 330.441 630.301 329.396 630.225 c 330.312 630.733 331.228 631.24 332.144 631.748 c 334.627 633.705 l 334.693 633.693 l 334.162 631.645 l f BT 9 0 0 8.9946 176.081 570.8428 Tm (F)Tj ET 165.462 559.686 26 5.153 re f 306.608 561.687 26 5.1529 re f BT 9 0 0 8.9946 211.516 570.8428 Tm (S)Tj ET 200.649 545.919 26 4.7142 re f 341.014 545.919 26 4.7142 re f BT 9 0 0 8.9946 242.833 570.8428 Tm [(F/S)-6920(F)-3320.9(S)-3143.1(F/S)]TJ ET 0 0 0 0.5 k /GS5 gs 235.837 546.027 26 2.4985 re f 235.837 562.517 26 2.4985 re f 377.548 554.771 26 2.4985 re f /Cs8 cs 1 scn /GS4 gs 377.548 562.517 26 2.4985 re f 377.548 547.276 26 2.4985 re f EMC Q q 1 i 0 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n /GS2 gs BT /F8 1 Tf 9 0 0 9 114 501.0394 Tm 0.017 g 0.151 Tc 0 Tw (\015 )Tj /F6 1 Tf 4.1692 0 TD -0.0056 Tc 0.0006 Tw [(1.6 )-253.2(S)13.5(t)-6.6(a)8.3(i)-0.6(nin)7.4(g)-0.6( f)8.3(o)11.6(r a deh)22.5(y)7.3(dr)12.5(og)7.5(enas)-8.6(e enzyme)5.5(, s)4.4(u)-0.8(c)5.4(h)-0.7( as g)-7.4(l)11.5(ucos)-8.6(e-6-p)6.4(hos)4.4(p)6.4(ha)18.3(t)5.4(e)]TJ -4.1692 -1.2222 TD 0.0005 Tw [(deh)22.6(y)7.4(dr)12.6(og)7.6(enas)-8.5(e)5.6(,)-0.5( a)8.4(f)-6.5(t)5.5(e)-0.5(r g)7.6(e)3.6(l elec)-7.4(tr)12.6(o)10.8(p)6.5(ho)11.7(r)12.6(e)-0.5(sis. 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I)15.7(f)-0.5( t)-6.4(h)3.6(es)-8.4(e r)12.7(e)-0.4(p)11.7(r)12.7(e-)]TJ T* 0.003 Tc -0.008 Tw [(s)-8.1(e)-0.1(n)18.8(t)-0.3( t)-6.1(h)-0.3(r)13(e)-5(e dif)-10(f)8.8(e)-0.1(r)13(e)-0.1(n)18.8(t)-0.3( alleles, six g)8(e)-0.1(no)11.1(typ)-9(e)-0.1(s a)8.7(r)13(e p)-9(o)-0.1(s)4.9(s)-0.3(ib)6.9(le)6(. B)-20(e)-5(ca)18.7(us)-8.1(e s)4.9(u)-0.3(c)5.9(h)-0.3( elec-)]TJ T* 0.0054 Tc 0.0844 Tw [(tr)13.9(o)12.1(p)7.7(ho)13(r)13.9(e)0.8(tic alleles a)9.7(r)13.9(e )]TJ /F3 1 Tf 9.1767 0 TD -0.0019 Tc 0 Tw [(codom)10.6(i)6.6(na)9.5(n)15.6(t)]TJ /F6 1 Tf 4.6969 0 TD 0.0035 Tc 0.0863 Tw [(, het)4.9(e)-1.1(r)12(o)5(zyg)7(o)10.2(t)4.9(e)-1.1(s a)7.8(n)3(d ho)11.1(mo)5(zyg)7(o)10.2(t)4.9(e)-1.1(s f)7.8(o)11.1(r)]TJ -13.8736 -1.1818 TD -0.0027 Tc -0.0023 Tw [(e)-5.6(a)0.1(c)6.3(h)0.1( allele co)12.5(m)10.2(b)12.5(ina)19.1(t)-4.8(io)12.5(n ca)9.1(n b)-8.5(e)0.3( s)-7.7(c)0.2(o)12.5(r)13.4(ed dir)13.4(ec)-6.6(t)-5.7(l)7.2(y f)-9.6(r)13.4(o)12.5(m)0.2( t)-5.7(h)4.3(e g)8.3(e)4.4(ls a)9.1(n)4.3(d co)11.5(un)19.2(t)6.2(e)-4.6(d)6.3(.)]TJ T* -0.0049 Tc -0.0228 Tw [(A s)5.1(p)-8.8(ecimen s)-7.9(e)0.1(t o)12.3(f)0( r)13.2(e)0.1(s)5.1(u)-5(l)12.2(ts is as f)9(o)7.2(llo)16.2(w)0.1(s:)]TJ /F1 1 Tf 1.0909 -1.7727 TD 0.0078 Tc 0 Tw [(Ge)18.2(n)12.9(o)21(t)17.1(y)5.1(pe)]TJ /F4 1 Tf 6.17 0 TD -0.0065 Tc [(SS)-1708.8(II)-1650.9(FF)-1732.8(SI)-1707.2(SF)-1704.4(IF)]TJ /F1 1 Tf 15.7098 0 TD -0.1072 Tc [(To)-94(t)-102.1(a)-106.9(l)]TJ -21.8798 -1.1818 TD -0.0104 Tc [(N)23.7(u)-5.3(mb)-16.3(er)]TJ /F6 1 Tf 6.1788 0 TD -0.0048 Tc [(12)-1601.9(21)-1601.9(60)-1743.2(34)-1686.5(46)-1714.9(77)-1996.8(250)]TJ -6.1788 -1.7727 TD 0.0049 Tc 0.0695 Tw [(Thes)-7.7(e g)8.4(e)0.3(no)11.6(typ)12.4(i)0.3(c da)19.2(t)-5.7(a)0.1( ca)9.2(n b)-8.5(e)0.3( r)13.4(e)-4.6(d)12.5(u)0.1(ced as f)9.2(o)7.4(llo)16.4(w)0.3(s t)6.3(o)0.3( a s)-7.7(e)0.3(t o)12.5(f)0.2( t)-5.7(h)4.3(e t)-5.7(h)0.2(r)13.4(e)-4.6(e)]TJ /F3 1 Tf -1.0909 -1.1818 TD 0.0007 Tc 0.0801 Tw [(a)7.2(l)1.3(le)12.1(le f)-11.9(r)15(eq)11.2(uencies)]TJ /F6 1 Tf 6.7076 0 TD 0.0055 Tc 0.0743 Tw [(. A gi)8(v)8.9(e)0.9(n allele \(e)7(.g., )]TJ /F3 1 Tf 8.6755 0 TD 0 Tc 0 Tw (S)Tj /F6 1 Tf 0.4726 0 TD 0.0048 Tc 0.075 Tw [(\) is p)12.3(r)13.3(es)-7.8(en)19.2(t in tw)8.2(o co)11.5(p)12.3(ies in t)-5.8(h)4.2(e)]TJ -15.8557 -1.1818 TD 0.0026 Tc 0.1346 Tw [(ho)10.2(mo)4.1(zyg)6.1(o)9.3(t)4(e)-2(s \()]TJ /F3 1 Tf 6.0413 0 TD 0.0045 Tc 0 Tw (SS)Tj /F6 1 Tf 0.9451 0 TD 0.1327 Tw [(, et)5.9(c.\) a)8.8(n)4(d o)12.1(n)4(e co)11.2(p)15.9(y)-0.3( in het)5.9(e)-0.1(r)13(o)6(zyg)8(o)11.2(t)5.9(e)-0.1(s \()]TJ /F3 1 Tf 16.133 0 TD -0.0035 Tc 0 Tw (SI)Tj /F6 1 Tf 0.8042 0 TD 0.0046 Tc 0.1326 Tw [(, et)6(c.\). W)37.9(i)12.2(t)-6(h)]TJ -23.9236 -1.1818 TD 0.0048 Tc 0.0524 Tw [(di)12.4(p)7.1(l)0.1(o)12.4(i)0.2(d)7.2(y)0( a)9.1(n)4.3(d a)19.1(u)12.2(t)6.2(o)0.2(s)-7.8(o)12.4(ma)-4.9(l inher)-5.7(i)12.4(t)-5.8(a)9.1(nce)6.3(,)0.2( e)-7.6(v)8.2(er)-28.7(y indi)7.3(vid)12.4(u)-2.9(a)-4.9(l)0.1( ca)9.1(r)-5.7(r)-5.7(ies a pa)19.1(t)6.2(e)0.2(r)-5.7(n)3.3(a)-4.9(l)]TJ T* -0.0031 Tc -0.0019 Tw [(a)7.2(n)2.4(d a ma)17.2(ter)-7.6(n)1.4(a)-6.8(l)-1.8( co)9.6(p)14.3(y)-1.9( a)17.2(t)-1.8( e)-7.6(a)-1.9(ch lo)-10.5(c)-8.6(u)1.3(s. W)36.2(i)10.5(t)-7.7(h)-1.8( )]TJ /F3 1 Tf 16.0441 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.6908 0 TD -0.0016 Tc -0.0034 Tw [(indi)6.9(vid)12(u)-3.3(als in a s)-6.2(a)8.7(m)18.8(p)6.7(le \(250 in)]TJ -16.7349 -1.1818 TD -0.005 Tc -0.0227 Tw [(t)-6(h)4(e p)12.1(r)13.1(es)-8(en)19(t cas)-8(e)0(\), t)-6(h)4(er)13.1(e a)8.9(r)13.1(e 2)]TJ /F3 1 Tf 11.0437 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.6645 0 TD -0.0054 Tc -0.0223 Tw [(g)7.7(e)-0.4(ne co)10.9(p)11.7(ies. 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An elec)-6.7(tr)13.4(o)11.5(p)7.2(ho)12.5(r)13.4(e)0.2(tic o)12.5(r)0.2( a)9.1(n)23.3(y o)11.5(t)-5.8(her kind o)12.5(f)0.1( mo)7.3(lec)-6.7(u)-4.9(la)9.1(r sur)-28.6(v)8.2(e)-7.6(y)0( o)12.5(f)0.1( g)8.3(e)0.2(netic va)9.1(r)-5.7(i)-2.7(a-)]TJ T* 0.0637 Tc 0 Tw [(t)54.1(i)59.1(o)71.3(n)59( y)56(i)59.1(e)63.2(l)59(d)62.2(s)59( d)56.1(a)78(t)53.1(a)58.9( o)71.3(n)59( t)53.1(h)63.1(e)59.1( n)78.1(u)58.9(m)69.1(b)50.3(e)59.1(r)65.1(s)59( o)71.3(f)59( e)53.2(a)58.9(c)65.1(h)59( g)67.2(e)59.1(n)63.2(o)70.4(t)56(y)58.9(p)50.2(e)59.1( i)59.1(n)59( a)58.9( s)53.1(a)68(m)78.1(p)66(l)59(e)59.1( o)71.3(f)59( i)59.1(n)63.2(d)59.1(i)66.2(v)56.1(i)59.1(d)71.3(u)56(a)54(l)62.1(s)]TJ T* 0.0022 Tc -0.0072 Tw [(f)-9.7(r)13.3(o)12.4(m)0.1( a p)-8.7(o)11.5(p)11.3(u)-4.9(la)19.1(tio)12.4(n)0.1(. 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A s)4.9(u)-0.3(r)-29(v)7.9(e)-7.9(y)-0.3( t)-6.1(h)2.9(a)18.8(t)-0.2( f)-10(i)-0.1(nds va)8.8(r)-6(i)-3.1(a)8.8(n)18.9(ts a)18.8(t)-0.2( 7/30 lo)-8.9(ci)6(, tw)7.9(o o)12.1(f)-0.2( w)-7(h)-0.2(ic)5.9(h a)8.8(r)13(e no)11.2(t co)12.1(n)7.9(s)-0.2(id-)]TJ T* -0.0018 Tc -0.0032 Tw [(er)12.3(ed p)-9.8(o)6.2(l)6.1(y)-4(mo)11.4(r)-10.7(p)6.1(hic b)15.2(y)-1.1( t)-6.9(h)-1(is cr)-6.8(i)11.3(t)5.1(er)-6.8(io)11.4(n, yields )]TJ /F3 1 Tf 16.6405 0 TD 0 Tc 0 Tw (P)Tj /F6 1 Tf 0.7753 0 TD -0.0011 Tc -0.0039 Tw (= 5/30 = 17% \()Tj /F1 1 Tf 5.8731 0 TD -0.0111 Tc 0.0059 Tw [(Pro)-3.2(b)-7.1(l)-16(e)-5(m)-10.1( 1)-10.4(.)-10.3(1)]TJ /F6 1 Tf 5.0473 0 TD -0.0008 Tc 0 Tw (\).)Tj -28.3361 -1.1818 TD -0.0052 Tc -0.0144 Tw [(W)11.9(h)-0.3(ile t)-6.2(h)-0.3(is me)-6.1(asur)12.9(e is q)9.6(u)-0.4(ic)5.8(k a)8.7(n)3.9(d co)12(n)22.9(v)7.8(enien)18.8(t t)5.8(o)-0.2( ca)-5.3(lc)-7.1(u)-5.3(l)-3.3(a)18.7(t)5.8(e)5.9(,)-0.2( t)-6.2(h)3.8(e a)8.7(r)-0.3(b)12(i)12(t)-5.2(ra)8.7(r)-29.1(y)-0.4( c)-7.1(u)11.8(t-)]TJ T* 0.0042 Tc 0.0735 Tw [(o)11.8(f)-10.3(f cr)-6.3(i)11.8(t)5.6(er)-6.3(io)11.8(n, w)-7.3(h)-0.5(ic)5.6(h dep)-9.3(ends en)18.6(tir)12.7(e)3.7(l)6.5(y)-0.6( o)11.8(n)-0.5( t)-6.4(h)3.6(e t)-6.4(a)2.6(st)5.6(e o)11.8(f)-0.5( t)-6.4(h)3.6(e in)22.7(v)7.6(e)-0.4(stiga)18.5(t)5.6(o)11.8(r)62.8(,)-0.4( is)]TJ T* -0.0054 Tc -0.0223 Tw [(un)7.6(s)-6.4(a)18.5(tisfac)-7.3(t)5.6(o)11.8(r)-29.3(y a)8.5(n)3.7(d ma)-5.5(k)8.6(e)-0.4(s i)11.8(t)-0.5( dif)-10.3(f)-10.3(i)-0.4(c)-7.3(u)-5.5(l)11.7(t)-0.5( t)5.6(o)-0.4( co)11.8(m)18.6(p)-5.4(a)8.5(r)12.7(e dif)-10.3(f)8.5(e)-0.4(r)12.7(e)-0.4(n)18.6(t)-0.5( st)9.5(udies.)]TJ 1.0909 -1.1818 TD -0.0053 Tc [(F)18.7(o)11.9(r t)-6.3(h)-0.4(is r)12.8(e)-6.2(as)-8.3(o)11.9(n)-0.4(, t)-6.3(h)3.7(e f)8.6(o)6.8(llo)15.8(w)-3.2(in)7.7(g met)-6.3(h)3.7(o)-9.1(d)2.8(s a)8.6(r)12.8(e p)11.8(r)12.8(ef)8.6(era)7.6(b)6.8(le)5.8(.)]TJ /F1 1 Tf 7.8067 -2.8636 TD 0.0495 Tc 0 Tw (B1.2.ii.)Tj /F2 1 Tf 3.6198 0 TD 0.0092 Tc 0.0003 Tw [(Al)-6.1(lele n)16.8(u)-0.4(m)8.6(b)-10.2(er \()]TJ /F5 1 Tf 6.4727 0 TD 0 Tc 0 Tw (A)Tj /F2 1 Tf 0.6744 0 TD (\))Tj /F6 1 Tf -19.6645 -1.7727 TD 0.005 Tc 0.0059 Tw [(F)19.4(o)12.6(r a gi)7.5(v)8.4(e)0.4(n lo)-8.4(c)-6.5(u)3.4(s, t)-5.6(h)4.4(e n)19.4(u)0.2(m)10.4(b)-8.4(er o)12.6(f)0.3( dif)-9.5(f)9.3(e)0.4(r)13.5(e)0.4(n)19.4(t)0.3( alleles in a s)-5.6(a)9.3(m)19.4(p)7.3(le is co)11.7(un)19.4(t)6.4(e)-4.5(d)6.5(,)]TJ 0 -1.1818 TD 0.0044 Tc 0.0446 Tw [(a)8.7(n)3.9(d t)-6.2(h)3.8(e me)-6.1(a)8.7(n)-0.3( ca)8.7(n b)-9(e)-0.2( t)-6.2(a)-5.3(k)8.8(e)-0.2(n o)15.9(v)7.8(er t)-6.2(h)3.8(e s)-8.2(e)-0.2(t o)12(f)-0.3( lo)-9(ci t)-6.2(h)2.8(a)18.7(t)-0.3( a)8.7(r)12.9(e st)9.7(udied)5.9(.)-0.2( F)18.8(o)12(r t)-6.2(h)3.8(e)]TJ T* -0.0045 Tc -0.0208 Tw [(exa)9.4(m)19.5(p)7.5(l)0.4(e o)12.7(f)0.4( allo)6.6(zyme va)9.4(r)-5.4(i)-2.5(a)9.4(n)19.5(ts in )]TJ /F1 1 Tf 12.5575 0 TD -0.0132 Tc -0.0115 Tw [(Fi)-8.1(g)-11.1(u)-8.1(re)-8( 1)-8.2(.)-8.1(6)]TJ /F6 1 Tf 4.1244 0 TD -0.0049 Tc -0.0204 Tw [(, t)-5.9(h)4.1(er)13.2(e a)9(r)13.2(e tw)8.1(o a)-5(l)-4.9(leles. 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M)27(o)13.1(r)14(e)0.9( im)19.9(p)-8(o)13.1(r)-8.9(t)-5.1(a)9.8(n)19.9(t)-5.1(l)7.8(y)73.7(,)0.9( t)-5.1(h)4.9(e)]TJ T* 0.0015 Tc -0.0065 Tw [(met)-6(h)4(o)-8.8(d)-0.1( det)5.9(ec)-6.9(ts o)12.2(n)-5(l)6.9(y)-0.2( a)8.8(mino acid c)6(h)3(a)8.8(n)7.9(g)8(e)-0.1(s t)-6(h)3(a)18.8(t)-0.2( a)8.8(f)-9.9(f)8.9(e)-4.9(c)-6.9(t)-0.2( t)-6(h)4(e mo)5.1(b)12.1(i)-5(li)12.1(ty o)12.2(f)-0.2( p)12(r)13.1(o)11.2(t)5.9(ein)7.9(s in)]TJ T* -0.0029 Tc -0.0021 Tw [(g)7.6(e)3.7(ls \(most)-6.5(l)6.5(y o)11.7(n)-5.5(l)6.5(y)-0.7( t)-6.5(h)3.5(os)-8.5(e ca)18.4(usin)7.5(g c)5.6(h)2.5(a)8.4(r)7.5(g)7.6(e)-0.5( c)5.6(h)2.5(a)8.4(n)7.5(g)7.6(e)-0.5(s\); t)-6.5(h)3.5(es)-8.5(e va)8.4(r)-6.4(i)-3.4(a)8.4(n)18.5(ts p)11.6(r)12.6(o)4.7(b)-5.4(a)7.4(b)6.6(l)6.4(y)-0.7( r)12.6(e)-0.5(p)11.6(r)12.6(e-)]TJ ET 0.902 g 114 294.406 342 389.594 re f BT 11 0 0 11 126 664.0051 Tm 0.017 g -0.0051 Tc -0.024 Tw [(The fac)-7(t)5.9(o)12.1(r)-0.2( o)12.1(f)-0.2( 2 a)8.8(r)-6(is)-8.1(es b)-8.9(e)-5(ca)18.8(us)-8.1(e t)-6.1(h)3.9(e o)12.1(r)13(der in w)-7(h)-0.2(ic)5.9(h t)-6.1(h)3.9(e tw)7.9(o a)-5.2(l)-5.1(leles a)8.8(r)13(e c)5.9(h)3.9(os)-8.1(en)]TJ T* -0.0053 Tc -0.0224 Tw [(is ir)-6.2(r)12.8(e)3.8(le)-8.1(va)8.6(n)18.7(t)-0.4(.)]TJ 1.0909 -1.1818 TD -0.0057 Tc -0.0188 Tw [(A q)9.1(u)-0.9(ic)5.3(k)8.3(e)-0.7(r wa)17.2(y o)11.5(f)-0.8( o)4.5(b)10.5(t)-6.7(a)8.2(inin)7.3(g t)-6.7(h)3.3(e s)-6.7(a)8.2(me r)12.4(e)-0.7(su)-5.8(l)11.4(t)-0.8( is t)5.3(o)-0.7( sub)10.5(t)-5.7(rac)-7.6(t)-0.8( f)-10.6(r)12.4(o)11.5(m)-0.8( 1 t)-6.7(h)3.3(e f)-10.6(r)12.4(e-)]TJ -1.0909 -1.1818 TD -0.0049 Tc -0.0228 Tw [(q)9.9(u)-0.1(enc)-15.8(y)-0.1( wi)12.3(t)-5.9(h)0( w)-6.8(h)0(ic)6.1(h a pa)9(ir o)12.3(f)0( a)-5(l)-4.9(leles is t)-5.9(h)4.1(e s)-5.9(a)9(me)6.2(, i)6.2(.)0.1(e)6.2(., t)6.1(o)0.1( ca)-5(lc)-6.8(u)-5(l)-3(a)19(t)6.1(e)]TJ /F3 1 Tf 6.8229 -1.7727 TD 0 Tc 0 Tw (H)Tj /F6 1 Tf 0.9365 0 TD -0.0049 Tc -0.0228 Tw (= 1 \(0.208\))Tj 7.7 0 0 6.6 266.0147 609.1351 Tm 0 Tc 0 Tw (2)Tj 11 0 0 11 271.8662 605.5051 Tm -0.0049 Tc -0.0228 Tw ( \(0.306\))Tj 7.7 0 0 6.6 310.5899 609.1351 Tm 0 Tc 0 Tw (2)Tj 11 0 0 11 316.4413 605.5051 Tm -0.0049 Tc -0.0228 Tw ( \(0.486\))Tj 7.7 0 0 6.6 355.165 609.1351 Tm 0 Tc 0 Tw (2)Tj 11 0 0 11 361.0165 605.5051 Tm -0.0049 Tc -0.0228 Tw (= 0.627)Tj -21.3651 -1.7727 TD 0.0012 Tc -0.0062 Tw [(T)97.7(o)-0.3( s)4.7(u)-0.5(mma)8.6(r)-6.2(ize t)-6.3(h)3.7(e r)12.8(e)-0.3(s)4.7(u)-5.4(l)11.8(t)-0.4(s f)8.6(o)11.9(r a s)-8.3(e)-0.3(t o)11.9(f)-0.4( lo)-9.1(ci)5.8(, w)7.7(e)-0.3( sim)18.7(p)6.6(l)6.6(y)-0.5( t)-6.3(a)-5.4(k)8.7(e)-0.3( t)-6.3(h)3.7(e me)-6.2(a)8.6(n)-0.4( o)11.9(f)-0.4( t)-6.3(h)3.7(e)]TJ /F3 1 Tf 0 -1.1818 TD 0 Tc 0 Tw (H)Tj /F6 1 Tf 0.9365 0 TD -0.0044 Tc -0.0233 Tw [(val)12.7(u)0.4(es f)9.5(o)12.8(r e)-5.3(a)0.4(c)6.6(h)0.5( lo)-8.2(c)-6.3(u)3.6(s \()]TJ /F1 1 Tf 8.5939 0 TD -0.0153 Tc -0.0116 Tw [(Pro)-3.1(b)-7.1(l)-16(e)-4.9(m)-10.1( 1)-10.3(.)-10.2(1)]TJ /F6 1 Tf 4.9832 0 TD -0.0048 Tc 0 Tw (\).)Tj /F3 1 Tf -13.4226 -1.1818 TD 0 Tc (H)Tj /F6 1 Tf 1.0533 0 TD 0.0045 Tc 0.0751 Tw [(me)-6(as)4.9(ur)13(es t)-6.1(h)3.9(e le)-7.9(v)7.9(e)4(l o)12.1(f)-0.2( va)8.8(r)-6(i)-3.1(a)7.8(b)12.1(ili)12.1(t)-3.2(y in a co)12.1(n)23(v)7.9(enien)18.9(t wa)17.8(y)72.7(,)-0.1( since alleles)]TJ -2.1442 -1.1818 TD -0.0051 Tc -0.0112 Tw [(p)12(r)13(es)-8.1(en)18.9(t a)18.8(t)-0.2( lo)16(w f)-10(r)13(eq)9.7(uencies co)12.1(n)18.9(t)-5.1(r)-6(i)4(b)11.1(u)11.9(t)5.9(e)-0.1( li)12.1(t)9.8(t)-6.1(le t)5.9(o)-0.1( i)12.1(ts val)12(u)-0.3(e; t)-6.1(h)-0.2(is me)-6(as)4.9(ur)13(e is als)-8.1(o)]TJ T* 0.0046 Tc 0.0581 Tw [(no)11.3(t s)5(t)-5(r)13.1(o)12.2(n)8(g)-6.8(l)6.9(y)-0.2( dep)-8.9(enden)19(t o)12.2(n)-0.1( t)-6(h)4(e s)-6(a)8.9(m)19(p)6.9(le size)6.1(. 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The va)9.8(r)-5(i)-2.1(a)9.8(n)19.9(ts det)6.9(ec)-6(t)6.9(e)-4(d a)9.8(r)14(e called r)14(e)0.9(s)5.9(t)-4.1(r)-5(i)0.9(c)-6(t)-4.1(io)13.1(n f)-9(r)0.8(a)5.9(g)-4(men)19.9(t)0.8( len)8.9(g)0.9(t)-5.1(h)0.8( p)-8(o)8(l)7.8(y)0.7(-)]TJ T* 0.0043 Tc 0.319 Tw [(mo)11.9(r)-10.1(p)6.6(hism)7.7(s \(RFLP)27.6(s\), a)8.6(n)3.8(d t)-6.3(h)3.7(e)-8.1(y)-0.5( a)8.6(r)12.8(e widel)6.6(y)-0.5( us)-8.3(ed in g)7.8(e)-0.3(netic ma)18.6(p)10.8(p)11.8(in)7.7(g. )]TJ /F3 1 Tf 30.1706 0 TD -0.0226 Tc 0 Tw (D.)Tj -30.1706 -1.1818 TD -0.0065 Tc [(m)5.5(e)14.5(la)14.4(n)5.4(ogas)8.4(t)8.4(e)-1.6(r)]TJ /F6 1 Tf 5.3294 0 TD -0.0054 Tc -0.0116 Tw [(was mos)4.6(t)-6.4(l)6.5(y)-0.6( us)-8.4(ed in t)-6.4(h)3.6(e e)-6.3(a)8.5(rl)6.5(y s)4.6(u)-0.6(r)-29.3(v)7.6(e)-8.2(y)-0.6(s o)11.8(f)-0.5( D)8.6(N)37.6(A va)8.5(r)-6.3(i)-3.4(a)18.5(t)-5.4(io)11.8(n, b)-9.2(e)-5.3(ca)18.5(us)-8.4(e o)11.8(f)]TJ -5.3294 -1.1818 TD 0.002 Tc -0.007 Tw [(t)-6.4(h)3.7(e a)7.5(b)11.8(ili)11.8(t)-3.4(y t)5.6(o)-0.3( cr)12.8(e)-6.2(a)18.5(t)5.6(e)-0.4( f)-16.3(l)-0.5(ies ho)11.9(mo)5.8(zyg)7.7(o)10.9(u)2.6(s f)8.6(o)11.9(r a)8.5(n)22.8(y o)11.9(f)-0.5( t)-6.4(h)3.7(e t)-6.4(h)-0.5(r)12.8(e)-5.3(e ma)18.5(jo)11.9(r c)5.7(h)-0.5(r)12.8(o)11.9(mos)-8.3(o)11.9(mes)]TJ T* -0.0052 Tc -0.0228 Tw [(as exp)6.8(l)-3.3(a)8.7(i)-0.2(ned in )]TJ /F1 1 Tf 6.0195 0 TD -0.0054 Tc -0.0218 Tw [(S)-12.2(e)-13.1(c)-6.1(t)4.9(i)-6.2(o)9.7(n 1.1.iii.b)]TJ /F6 1 Tf 6.3967 0 TD -0.0225 Tw [(. 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-1.0693 TD (1)Tj 0.0084 -1.25 TD (T)Tj 0 -1.0783 TD (T)Tj 0 -3.2341 TD (T)Tj 0 -1.0783 TD (T)Tj T* (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj 0 8.6252 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 239.095 520.2383 Tm (G)Tj 0 6.1113 -6.1113 0 137.2425 610.2738 Tm (2)Tj 0 -1.0692 TD (0)Tj 0 -1.0697 TD (1)Tj 0 -1.0693 TD (5)Tj -0.0667 -1.25 TD (G)Tj 0 -1.0783 TD (G)Tj 0 -3.2341 TD (G)Tj 0 -1.0783 TD (G)Tj T* (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0.017 8.6252 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 239.095 609.4222 Tm (G)Tj 0 6.1113 -6.1113 0 137.2425 623.0132 Tm (2)Tj 0 -1.0692 TD (0)Tj 0 -1.0697 TD (3)Tj 0 -1.0693 TD (1)Tj 0.0081 -1.25 TD (T)Tj 0 -1.0783 TD (T)Tj 0 -3.2341 TD (T)Tj 0 -1.0783 TD (T)Tj T* (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj 0 8.6252 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 239.095 622.1628 Tm (G)Tj 0 6.1113 -6.1113 0 137.2425 635.7538 Tm (2)Tj 0 -1.0692 TD (0)Tj 0 -1.0697 TD (5)Tj 0 -1.0693 TD (9)Tj -0.0495 -1.25 TD (A)Tj 0 -1.0783 TD (A)Tj 0 -3.2341 TD (A)Tj 0 -1.0783 TD (A)Tj T* (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj 0 8.6252 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 239.095 634.9069 Tm (G)Tj 0 6.1113 -6.1113 0 137.2425 648.4955 Tm (2)Tj 0 -1.0692 TD (1)Tj 0 -1.0697 TD (6)Tj 0 -1.0693 TD (6)Tj 0.0079 -1.25 TD (T)Tj 0 -1.0783 TD (T)Tj 0 -3.2341 TD (T)Tj 0 -1.0783 TD (T)Tj T* (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj 0 8.6252 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 239.095 647.6462 Tm (G)Tj 0 6.1113 -6.1113 0 143.7764 304.4989 Tm (4)Tj 0 -1.0697 TD (9)Tj 0 -1.0693 TD (8)Tj -0.0337 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 304.1613 Tm (T)Tj 0 6.1113 -6.1113 0 143.7764 329.98 Tm (5)Tj 0 -1.0697 TD (4)Tj 0 -1.0693 TD (7)Tj -0.0335 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 329.6424 Tm (T)Tj 0 6.1113 -6.1113 0 143.7764 355.46 Tm (8)Tj 0 -1.0697 TD (2)Tj 0 -1.0693 TD (3)Tj -0.0665 -1.25 TD (G)Tj 0 -1.0783 TD (G)Tj 0 -3.2341 TD (G)Tj 0 -1.0783 TD (G)Tj T* (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6252 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 239.095 355.1235 Tm (T)Tj 0 6.1113 -6.1113 0 143.7764 406.4235 Tm (9)Tj 0 -1.0697 TD (4)Tj 0 -1.0693 TD (5)Tj -0.0335 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 406.0858 Tm (T)Tj 0 6.1113 -6.1113 0 137.2425 444.6452 Tm (1)Tj 0 -1.0692 TD (0)Tj 0 -1.0697 TD (8)Tj 0 -1.0693 TD (7)Tj -0.0667 -1.25 TD (G)Tj 0 -1.0783 TD (G)Tj 0 -3.2341 TD (G)Tj 0 -1.0783 TD (G)Tj T* (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6252 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 239.095 444.3064 Tm (T)Tj 0 6.1113 -6.1113 0 137.2425 495.6075 Tm (1)Tj 0 -1.0692 TD (3)Tj 0 -1.0697 TD (0)Tj 0 -1.0693 TD (9)Tj -0.0337 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 495.2698 Tm (T)Tj 0 6.1113 -6.1113 0 137.2425 546.5709 Tm (1)Tj 0 -1.0692 TD (5)Tj 0 -1.0697 TD (9)Tj 0 -1.0693 TD (9)Tj -0.0339 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 546.2321 Tm (T)Tj 0 6.1113 -6.1113 0 137.2425 559.3104 Tm (1)Tj 0 -1.0692 TD (6)Tj 0 -1.0697 TD (3)Tj 0 -1.0693 TD (6)Tj -0.0335 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 558.9727 Tm (T)Tj 0 6.1113 -6.1113 0 137.2425 597.5332 Tm (1)Tj 0 -1.0692 TD (9)Tj 0 -1.0697 TD (7)Tj 0 -1.0693 TD (0)Tj -0.0339 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 597.1945 Tm (T)Tj 0 6.1113 -6.1113 0 143.7764 317.2394 Tm (5)Tj 0 -1.0697 TD (1)Tj 0 -1.0693 TD (4)Tj 0.008 -1.25 TD (T)Tj 0 -1.0783 TD (T)Tj 0 -3.2341 TD (T)Tj 0 -1.0783 TD (T)Tj T* (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj 0 8.6252 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 239.095 316.6729 Tm (C)Tj 0 6.1113 -6.1113 0 143.7764 342.7195 Tm (7)Tj 0 -1.0697 TD (1)Tj 0 -1.0693 TD (2)Tj -0.0663 -1.25 TD (G)Tj 0 -1.0783 TD (G)Tj 0 -3.2341 TD (G)Tj 0 -1.0783 TD (G)Tj T* (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6252 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 239.095 342.1541 Tm (C)Tj 0 6.1113 -6.1113 0 143.7764 368.2017 Tm (9)Tj 0 -1.0697 TD (0)Tj 0 -1.0693 TD (6)Tj -0.0493 -1.25 TD (A)Tj 0 -1.0783 TD (A)Tj 0 -3.2341 TD (A)Tj 0 -1.0783 TD (A)Tj T* (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj 0 8.6252 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 239.095 367.6352 Tm (C)Tj 0 6.1113 -6.1113 0 143.7764 419.164 Tm (9)Tj 0 -1.0697 TD (4)Tj 0 -1.0693 TD (8)Tj -0.0665 -1.25 TD (G)Tj 0 -1.0783 TD (G)Tj 0 -3.2341 TD (G)Tj 0 -1.0783 TD (G)Tj T* (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6252 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 239.095 418.5975 Tm (C)Tj 0 6.1113 -6.1113 0 137.2425 470.1263 Tm (1)Tj 0 -1.0692 TD (1)Tj 0 -1.0697 TD (2)Tj 0 -1.0693 TD (9)Tj -0.0665 -1.25 TD (G)Tj 0 -1.0783 TD (G)Tj 0 -3.2341 TD (G)Tj 0 -1.0783 TD (G)Tj T* (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6252 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 239.095 469.5598 Tm (C)Tj 0 6.1113 -6.1113 0 137.2425 533.8303 Tm (1)Tj 0 -1.0692 TD (5)Tj 0 -1.0697 TD (9)Tj 0 -1.0693 TD (1)Tj -0.0498 -1.25 TD (A)Tj 0 -1.0783 TD (A)Tj 0 -3.2341 TD (A)Tj 0 -1.0783 TD (A)Tj T* (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj 0 8.6252 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 239.095 533.2638 Tm (C)Tj 0 6.1113 -6.1113 0 137.2425 572.0509 Tm (1)Tj 0 -1.0692 TD (6)Tj 0 -1.0697 TD (5)Tj 0 -1.0693 TD (6)Tj -0.0332 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0.0414 -1.0781 TD (T)Tj -0.0414 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj 0 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 571.4844 Tm (C)Tj 0 6.1113 -6.1113 0 137.2425 584.7926 Tm (1)Tj 0 -1.0692 TD (7)Tj 0 -1.0697 TD (9)Tj 0 -1.0693 TD (9)Tj -0.0337 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj -0.033 -1.0781 TD (G)Tj T* (G)Tj 0.033 8.6252 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 239.095 584.2261 Tm (C)Tj 0 6.1113 -6.1113 0 137.2425 661.2349 Tm (2)Tj 0 -1.0692 TD (1)Tj 0 -1.0697 TD (7)Tj 0 -1.0693 TD (8)Tj -0.0335 -1.25 TD (C)Tj 0 -1.0783 TD (C)Tj 0 -3.2341 TD (C)Tj 0 -1.0783 TD (C)Tj T* (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0.0414 8.6252 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 239.095 660.6696 Tm (C)Tj 0 6.1113 -6.1113 0 238.7585 162.2194 Tm 0.0022 Tc [(Chim)21.2(pa)11.1(nzee)]TJ 0.7136 14.4474 TD 0 Tc [(H)24(a)19(p)7(l)0(o)11(t)-3(yp)-9(e)]TJ 0.8915 -1 TD 0.0049 Tc [(gr)17.9(o)15.9(u)16.9(p)]TJ 5.1726 3.1039 TD 0 Tc [(N)35(u)0.1(m)10(b)-9(er in)]TJ 0.8025 -1 TD 0.006 Tc [(sa)15(m)25(p)13(l)6.1(e)]TJ /F3 1 Tf -7.9134 0.9792 TD 0.001 Tc -0.001 Tw [(H)32(o)11(m)8(o)1.1( sa)11.9(p)11(i)5(ens)]TJ ET 0 0 0 0.14999 k /GS5 gs 380.023 350.78 13.433 12.86 re f 380.023 287.343 6.875 12.763 re f 326.166 338.43 6.8762 12.477 re f 333.042 376.625 6.875 12.477 re f 359.969 389.421 6.8762 12.477 re f 353.285 478.417 6.8762 12.478 re f 333.042 453.017 6.875 12.668 re f 319.863 503.818 13.179 12.668 re f 359.969 542.012 19.863 12.671 re f 319.735 592.879 13.369 12.795 re f 326.039 644.062 7.065 12.412 re f 0 0 0 0.34 k 393.326 236.319 9.3895 50.802 re f 393.454 300.107 9.3575 38.195 re f 393.454 363.514 9.3575 12.857 re f 393.531 401.836 9.3117 50.929 re f 393.519 465.498 9.4204 12.923 re f 393.615 490.898 9.3242 12.923 re f 393.436 516.49 9.5016 25.527 re f 393.453 605.548 9.742 38.385 re f 393.358 656.54 9.5508 13.177 re f 393.453 554.747 9.742 38.195 re f 0 0 0 0.21999 K 0.286 w 293.064 200.415 m 402.885 200.415 l 293.063 249.057 m 402.884 249.057 l 293.063 261.794 m 402.884 261.794 l 293.063 274.532 m 402.884 274.532 l 293.063 287.27 m 393.454 287.27 l 293.063 300.007 m 403.075 300.007 l 293.063 312.745 m 402.979 312.745 l 293.063 325.483 m 402.789 325.483 l 293.063 338.22 m 393.454 338.22 l 293.063 350.958 m 402.789 350.958 l 293.063 363.695 m 402.811 363.695 l 293.063 376.433 m 402.811 376.433 l 293.063 389.171 m 402.884 389.171 l 293.063 401.908 m 402.843 401.908 l 293.063 414.647 m 402.789 414.647 l 293.063 427.384 m 402.884 427.384 l 293.063 440.121 m 402.979 440.121 l 293.063 452.86 m 402.843 452.86 l 293.063 465.596 m 402.914 465.596 l 293.063 478.335 m 402.979 478.335 l 293.063 491.073 m 402.939 491.073 l 293.063 503.81 m 402.801 503.81 l 293.063 516.547 m 402.71 516.547 l 293.063 529.286 m 402.789 529.286 l 293.063 542.021 m 402.938 542.021 l 293.063 554.76 m 402.789 554.76 l 293.063 567.497 m 402.884 567.497 l 293.063 580.235 m 402.979 580.235 l 293.063 592.974 m 402.789 592.974 l 293.063 605.711 m 402.693 605.711 l 293.063 618.449 m 402.789 618.449 l 293.063 631.187 m 402.801 631.187 l 293.063 643.923 m 402.992 643.923 l 293.063 656.661 m 402.908 656.661 l 299.745 157.126 m 299.745 669.414 l 306.429 157.126 m 306.429 669.414 l 313.114 157.126 m 313.114 669.414 l S 0 0 0 0.64999 K 0.572 w 319.798 157.126 m 319.798 669.414 l S 0 0 0 0.21999 K 0.286 w 326.483 157.126 m 326.483 669.414 l 333.167 157.126 m 333.167 669.414 l 339.851 157.126 m 339.851 669.414 l 346.536 157.126 m 346.536 669.414 l 353.22 157.126 m 353.22 669.414 l 359.904 157.126 m 359.904 669.414 l 366.589 157.126 m 366.589 669.414 l 373.274 157.126 m 373.274 669.414 l 379.957 157.126 m 379.957 669.414 l 386.64 157.126 m 386.64 669.414 l 393.507 157.126 m 393.507 669.414 l S 0 0 0 0.64999 K 0.572 w 402.744 669.397 m 293.208 669.397 l 293.067 669.414 l 293.067 236.319 l 402.864 236.319 l 402.864 669.414 l 402.744 669.397 l h 402.864 236.319 m 402.864 157.062 l 292.999 157.062 l 292.999 236.319 l S /GS4 gs BT /F6 1 Tf 0 6.1113 -6.1113 0 318.2898 241.3039 Tm /Cs8 cs 1 scn 0 Tc 0 Tw (0)Tj -0.0493 -1.2499 TD (T)Tj 0 -1.0781 TD (T)Tj 0 -3.2346 TD (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj -0.0172 -1.0781 TD (T)Tj T* (T)Tj 0.0172 8.6253 TD (T)Tj 0 -1.0781 TD (T)Tj -10.4064 3.2344 TD (B)Tj 0 -1.0781 TD (B)Tj 0 -3.2346 TD (B)Tj 0 -1.0781 TD (B)Tj T* (B)Tj T* (B)Tj T* (B)Tj -0.017 -1.0781 TD -0.044 Tc (A)Tj T* 0 Tc (A+)Tj 0.017 8.6253 TD (B)Tj 0 -1.0781 TD (B)Tj 0 7.2572 -7.2572 0 400.5358 240.5646 Tm (C)Tj 0 6.1113 -6.1113 0 325.9282 216.747 Tm (24)Tj 0.2502 -1.0781 TD (4)Tj 0 -3.2346 TD (2)Tj 0 -1.0781 TD (4)Tj T* (2)Tj T* (1)Tj T* (1)Tj -0.0173 -1.0781 TD (7)Tj T* (2)Tj 0.0173 8.6253 TD (2)Tj 0 -1.0781 TD (2)Tj 0 7.2572 -7.2572 0 400.5358 217.8378 Tm (1)Tj 0 6.1113 -6.1113 0 318.2898 432.4128 Tm (8)Tj -0.0494 -1.2499 TD (T)Tj 0 -1.0781 TD (T)Tj 0 -3.2346 TD (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj -0.017 -1.0781 TD (T)Tj T* (T)Tj 0.017 8.6253 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 400.5358 431.6723 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 483.3751 Tm (6)Tj -0.0661 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (T)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 482.6368 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 508.8585 Tm (2)Tj -0.0667 -1.2499 TD (T)Tj 0 -1.0781 TD (T)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 508.1169 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 254.0448 Tm (0)Tj -0.0494 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 253.1954 Tm (G)Tj 0 6.1113 -6.1113 0 318.2898 266.7853 Tm (7)Tj -0.0496 -1.2499 TD (A)Tj 0 -1.0781 TD (A)Tj 0 -3.2346 TD (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj 0 8.6253 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 400.5358 265.937 Tm (T)Tj 0 6.1113 -6.1113 0 318.2898 279.527 Tm (0)Tj -0.0667 -1.2499 TD (A)Tj 0 -1.0781 TD (A)Tj 0 -3.2346 TD (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj 0.0172 -1.0781 TD (A)Tj -0.0172 -1.0781 TD (A)Tj 0 8.6253 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 400.5358 278.6767 Tm (G)Tj 0 6.1113 -6.1113 0 318.2898 292.2676 Tm (5)Tj -0.0498 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (T)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 291.4172 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 381.4505 Tm (6)Tj 0.008 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (T)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 380.6012 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 394.1922 Tm (5)Tj -0.0335 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (A)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 393.343 Tm (G)Tj 0 6.1113 -6.1113 0 318.2898 457.8951 Tm (7)Tj -0.0496 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (A)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 457.0459 Tm (G)Tj 0 6.1113 -6.1113 0 318.2898 521.5979 Tm (7)Tj 0.0083 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 520.7476 Tm (T)Tj 0 6.1113 -6.1113 0 318.2898 610.7808 Tm (5)Tj -0.0665 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0.0172 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 609.9315 Tm (A)Tj 0 6.1113 -6.1113 0 318.2898 623.5225 Tm (7)Tj 0.0079 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 622.6721 Tm (A)Tj 0 6.1113 -6.1113 0 318.2898 636.2631 Tm (8)Tj -0.0494 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 635.415 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 649.0037 Tm (4)Tj 0.0077 -1.2499 TD (C)Tj 0 -1.0781 TD (T)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 648.1567 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 305.007 Tm (0)Tj -0.0333 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 304.6705 Tm (T)Tj 0 6.1113 -6.1113 0 318.2898 330.4882 Tm (8)Tj -0.0335 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 330.1517 Tm (A)Tj 0 6.1113 -6.1113 0 318.2898 355.9693 Tm (2)Tj -0.0667 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (T)Tj T* (T)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 355.6317 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 406.9316 Tm (2)Tj -0.0335 -1.2499 TD (T)Tj 0 -1.0781 TD (T)Tj 0 -3.2346 TD (T)Tj 0 -1.0781 TD (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj T* (T)Tj 0 8.6253 TD (T)Tj 0 -1.0781 TD (T)Tj 0 7.2572 -7.2572 0 400.5358 406.594 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 445.1534 Tm (9)Tj -0.0667 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 444.8168 Tm (A)Tj 0 6.1113 -6.1113 0 318.2898 496.1168 Tm (0)Tj -0.0337 -1.2499 TD (G)Tj 0 -1.0781 TD (G)Tj 0 -3.2346 TD (G)Tj 0 -1.0781 TD (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 495.778 Tm (A)Tj 0 6.1113 -6.1113 0 318.2898 547.079 Tm (1)Tj -0.0335 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (T)Tj T* (T)Tj T* (T)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 546.7403 Tm (C)Tj 0 6.1113 -6.1113 0 318.2898 559.8174 Tm (2)Tj -0.0333 -1.2499 TD (A)Tj 0 -1.0781 TD (A)Tj 0 -3.2346 TD (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj 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(G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj T* (G)Tj 0 8.6253 TD (G)Tj 0 -1.0781 TD (G)Tj 0 7.2572 -7.2572 0 400.5358 368.1434 Tm (A)Tj 0 6.1113 -6.1113 0 318.2898 419.6733 Tm (4)Tj -0.0665 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 419.1068 Tm (T)Tj 0 6.1113 -6.1113 0 318.2898 470.6345 Tm (6)Tj -0.0661 -1.2499 TD (A)Tj 0 -1.0781 TD (A)Tj 0 -3.2346 TD (A)Tj 0 -1.0781 TD (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj T* (A)Tj 0 8.6253 TD (A)Tj 0 -1.0781 TD (A)Tj 0 7.2572 -7.2572 0 400.5358 470.0691 Tm (G)Tj 0 6.1113 -6.1113 0 318.2898 534.3373 Tm (5)Tj -0.0494 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 TD (C)Tj 0 -1.0781 TD (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj T* (C)Tj 0 8.6253 TD (C)Tj 0 -1.0781 TD (C)Tj 0 7.2572 -7.2572 0 400.5358 533.772 Tm (T)Tj 0 6.1113 -6.1113 0 318.2898 572.5602 Tm (0)Tj -0.0335 -1.2499 TD (C)Tj 0 -1.0781 TD (C)Tj 0 -3.2346 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I)15.8(n)-0.4( sp)-9.2(ecies w)-7.2(h)3.7(er)12.8(e s)-8.3(e)-5.2(q)9.5(u)-0.5(ence va)8.6(r)-6.2(i)-3.3(a)7.6(b)11.9(il-)]TJ -14.1176 -1.1818 TD -0.0006 Tc -0.0044 Tw [(i)11.3(t)-3.9(y is b)-9.7(ein)7.1(g in)18.1(t)5.1(e)-0.9(n)7.1(s)-1(i)6.2(v)7.1(el)6.1(y st)9(udied)5.2(,)-0.9( suc)5.2(h)-1( as )]TJ /F3 1 Tf 15.5153 0 TD 0.0041 Tc 0 Tw [(Dr)22.7(o)9.8(s)0.8(o)12.7(p)13.8(h)20.7(i)8.8(l)8(a)]TJ /F6 1 Tf 4.5221 0 TD -0.0008 Tc -0.0042 Tw [(a)7.8(n)3(d h)17.8(u)-1.3(ma)7.8(n)6.9(s)-1.2(, i)11.1(t)-1.2( is no)15.1(w co)11.2(m-)]TJ -20.0374 -1.1818 TD 0.0376 Tc 0.0009 Tw [(m)37.1(o)45.2(n)52(p)39.9(l)29.9(a)32.8(c)32.9(e)33( t)39(o)33( s)38(u)32.8(rv)41(e)25.2(y)32.8( m)36.1(a)41.9(n)56.1(y)32.8( d)33(i)33(f)23.1(f)41.9(e)33(r)46.1(e)33(n)52(t)32.9( s)38(t)28(r)46.1(e)33(t)39(c)39(h)37(e)33(s)32.9( o)45.2(f)32.9( D)42(N)71(A)32.9( a)41.9(r)46.1(o)44.3(u)32.8(n)37.1(d)33( t)27(h)37(e)33( g)41.1(e)33(n)37.1(o)45.2(m)37.1(e)33( f)41.9(o)45.2(r)]TJ T* 0.0014 Tc -0.0064 Tw [(t)-5.4(h)4.6(eir pa)19.4(t)10.4(t)6.5(er)-5.3(n)8.5(s)0.4( o)12.8(f)0.5( va)9.4(r)-5.3(i)-2.4(a)8.5(b)12.8(ili)12.8(t)-2.5(y)73.4(.)0.6( F)19.6(o)12.8(r h)19.5(u)0.4(ma)9.4(n p)-8.3(o)11.8(p)11.7(u)-4.5(la)19.4(tio)12.8(n)8.5(s, a)9.4(n)4.6(d f)9.5(o)12.8(r o)12.8(r)8.6(ga)9.4(nism)8.6(s o)12.8(f)0.5( eco-)]TJ T* -0.0051 Tc -0.0198 Tw [(no)12.1(mic o)12.1(r)-0.2( medica)-5.2(l)-0.2( signif)-10(ica)8.8(n)4(ce)6(, vast r)13(e)-0.1(s)-8.1(o)11.2(ur)13(ces ha)17.8(v)7.9(e)-0.1( b)-8.9(e)-5(en made a)17.8(v)-0.2(a)8.8(i)-5(la)7.8(b)7(l)-0.2(e t)5.9(o)-0.1( c)5.9(h)2.9(a)8.8(r)-0.2(-)]TJ T* 0.005 Tc 0 Tw [(ac)-6.5(t)6.4(e)0.4(r)-5.5(i)0.4(ze D)9.4(N)38.4(A s)-7.6(e)-4.5(q)10.2(u)0.2(ence va)9.3(r)-5.5(i)-2.6(a)8.3(b)12.6(ili)12.6(t)-2.7(y)73.2(.)0.4( S)-13.6(e)-7.4(v)8.4(e)0.4(ral millio)12.6(n S)12.5(N)0.3(P)28.3(s)0.3( a)9.3(r)13.5(e no)16.5(w a)18.3(v)0.3(a)9.3(i)-4.5(la)8.3(b)7.5(l)0.3(e f)9.3(o)12.6(r)]TJ T* 0.0043 Tc 0.0562 Tw [(us)-8.3(e in st)9.6(udies o)11.9(f)-0.4( h)18.6(u)-0.5(ma)8.6(n)7.7(s)-0.4(, a)8.6(n)3.8(d sp)-9.2(ecia)-5.4(l t)5.7(e)-5.2(c)5.7(hniq)9.5(u)-0.5(es a)8.6(r)12.8(e a)17.6(v)-0.4(a)8.6(i)-5.2(la)7.6(b)6.8(l)-0.4(e t)-6.3(h)2.7(a)18.6(t)-0.4( a)17.6(v)7.7(o)11.9(id t)-6.3(h)3.7(e)]TJ T* -0.0016 Tc -0.0034 Tw [(la)7.1(b)-9.6(o)11.4(r o)11.4(f)-0.9( r)12.3(e)-0.8(s)-8.8(e)-5.7(q)9(u)-1(encin)7.2(g)-0.8( t)-6.8(h)3.2(e s)-6.8(a)8(me p)11.3(i)-0.8(eces o)11.4(f)-0.9( D)8.1(N)37.1(A m)18.2(u)-5.9(l)11.3(t)-5.8(i)11.4(p)6.1(le times, b)10.4(u)11.2(t in)7.2(st)5.2(e)-6.7(a)-1(d p)11.3(r)12.3(o-)]TJ T* -0.0048 Tc -0.0083 Tw [(vide ef)-9.7(f)-9.7(i)0.2(cien)19.2(t me)-5.7(a)9.1(n)8.2(s o)12.4(f)0.1( det)6.2(ec)-6.7(tin)8.2(g)0.2( kno)16.3(w)-2.7(n S)12.3(N)0.1(P)28.1(s)0.1(. The p)12.3(r)-5.7(inci)12.4(pa)-4.9(l met)-5.8(h)4.2(o)-8.6(d)3.3(s o)12.4(f)0.1( a)9.1(n)3.3(a)-4.9(l)7.1(y-)]TJ T* -0.0059 Tc -0.0085 Tw [(sis r)12.2(e)-0.9(ma)8(in t)-6.9(h)3.1(e s)-6.9(a)8(me)5.2(, ho)15.2(w)7.1(e)-8.7(v)7.1(e)-0.9(r)62.3(,)-0.9( r)12.2(ega)8(r)12.2(d)-5.8(less o)11.3(f)-1( t)-6.9(h)3.1(e sizes o)11.3(f)-1( t)-6.9(h)3.1(e st)9(udies a)8(n)3.2(d t)-6.9(h)3.1(e t)5.1(e)-5.8(c)5.1(h)-1(-)]TJ T* -0.0049 Tc -0.0228 Tw [(no)7.2(logies us)-7.9(ed)6.2(.)]TJ 1.0909 -1.1818 TD 0.0041 Tc 0.0864 Tw [(Ther)12.6(e is, ho)15.6(w)7.5(e)-8.3(v)7.5(e)-0.5(r)62.7(,)-0.5( a)8.4(n)-0.6( im)18.5(p)-9.4(o)11.7(r)-10.3(t)-6.5(a)8.4(n)18.5(t dif)-10.4(f)8.4(e)-0.5(r)12.6(e)-0.5(nce b)-9.3(e)-0.5(tw)7.5(een r)12.6(e)-0.5(s)-8.5(e)-5.4(q)9.3(u)-0.7(encin)7.5(g)-0.5( st)9.4(udies)]TJ -1.0909 -1.1818 TD 0.005 Tc 0.0976 Tw [(a)9.3(n)4.5(d S)12.5(N)0.3(P det)6.4(ec)-6.5(tio)12.6(n)0.3(: t)-5.6(h)4.4(e va)9.3(r)-5.5(i)-2.6(a)9.3(n)19.4(ts det)6.4(ec)-6.5(t)6.4(e)-4.5(d in p)12.5(r)13.5(elimina)9.3(r)-28.5(y sur)-28.5(v)8.4(e)-7.4(y)0.2(s t)6.4(o)0.4( iden)19.4(tif)-16.5(y)]TJ T* 0.0043 Tc 0.08 Tw [(S)11.8(N)-0.4(P)27.6(s)-0.4( f)8.6(o)11.9(r us)-8.3(e in la)18.6(t)5.7(e)-0.3(r st)9.6(udies o)11.9(f)-0.4( la)8.6(r)7.7(g)7.8(er s)-6.3(a)8.6(m)18.7(p)6.6(les t)5.7(e)-0.3(nd t)5.7(o)-0.3( b)-9.1(e)-0.3( co)11.9(mmo)11.9(n)-0.4( va)8.6(r)-6.2(i)-3.3(a)8.6(n)18.7(ts,)]TJ T* -0.0044 Tc -0.0115 Tw [(since a small s)-5.4(a)9.5(m)19.6(p)7.6(le is unlik)9.6(e)4.7(l)7.5(y)0.4( t)6.6(o)0.6( co)12.8(n)19.6(t)-5.4(a)9.5(i)0.6(n ra)9.5(r)13.7(e)0.6( va)9.5(r)-5.3(i)-2.4(a)9.5(n)19.6(ts. S)12.7(N)0.5(P det)6.6(ec)-6.3(tio)12.8(n)0.5( ca)9.5(n t)-5.4(h)19.5(us)]TJ T* 0.0042 Tc 0.0428 Tw [(b)-9.2(e)-0.4( us)-8.4(ef)-6.4(u)-5.5(l)-0.5( f)8.5(o)11.8(r co)11.8(m)18.6(p)-5.4(a)8.5(r)-6.3(in)7.6(g di)6.7(v)7.6(e)-0.4(r)5.6(s)-0.5(i)11.8(t)-3.5(y le)-8.2(v)7.6(e)3.7(ls \(w)7.6(e sha)-5.5(l)-5.4(l s)-8.4(e)-5.3(e in t)-6.4(h)3.6(e next s)-8.4(e)-5.3(c)-7.3(t)-5.4(io)11.8(n t)-6.4(h)2.6(a)18.5(t)]TJ T* 0.0047 Tc 0.0951 Tw [(ra)9(r)13.2(e)0.1( va)9(r)-5.8(i)-2.9(a)9(n)19.1(ts co)12.3(n)19.1(t)-4.9(r)-5.8(i)4.2(b)11.3(u)12.1(t)6.1(e)0.1( li)12.3(t)10(t)-5.9(le t)6.1(o)0.1( di)7.2(v)8.1(e)0.1(r)6.1(s)0(i)12.3(t)-3(y me)-5.8(as)5.1(ur)13.2(es\). B)7.1(u)12.1(t f)9(o)12.3(r f)-5.9(u)-5(ll p)-8.8(o)11.4(p)11.2(u)-5(la)19(tio)12.3(n)]TJ T* -0.0055 Tc -0.0192 Tw [(g)7.6(e)-0.5(netic st)9.4(udies, t)-6.5(h)-0.6(is f)-10.4(r)12.6(eq)9.3(uenc)-16.4(y b)11.7(i)-3.5(as ca)18.4(us)-8.5(es s)-8.5(e)-0.5(r)-6.4(i)-0.5(o)10.8(u)2.5(s p)11.6(r)12.6(o)4.7(b)6.6(lem)7.5(s)-0.6(. A)15.5(s)-0.6( w)7.5(e)-0.5( sho)15.6(w in )]TJ /F1 1 Tf 29.3757 0 TD 0.0073 Tc 0 Tw [(Sec)12.4(-)]TJ -29.3757 -1.1818 TD -0.01 Tc 0.0048 Tw [(ti)-12.3(on)-6.4( 6)-6.5(.)-6.4(4)]TJ /F6 1 Tf 3.1566 0 TD -0.0035 Tc -0.0015 Tw [(, inf)9(o)12.3(r)-5.9(ma)18.9(tio)12.3(n)0( a)7.9(b)-8.7(o)11.3(u)12.1(t va)8.9(r)-5.9(i)-2.9(a)8.9(n)19(t f)-9.8(r)13.2(eq)9.9(uencies ca)8.9(n b)-8.7(e)0( v)8(e)0(r)-28.8(y)-0.1( us)-7.9(ef)-5.9(ul f)9(o)12.3(r inf)9(er)-5.9(r)-5.9(i)0(n)8(g)]TJ -3.1566 -1.1818 TD 0.0043 Tc 0.0596 Tw [(w)-7.2(h)3.7(et)-6.3(her s)-8.3(e)3.8(lec)-7.2(t)-5.3(io)11.9(n has b)-9.1(e)-5.2(en ac)-7.2(tin)7.7(g)-0.3( o)11.9(n)-0.4( a g)7.8(e)-0.3(ne)5.8(, a)8.6(n)3.8(d w)-7.2(h)2.7(a)18.6(t)-0.4( kind o)11.9(f)-0.4( s)-8.3(e)3.8(lec)-7.2(t)-5.3(io)11.9(n has)]TJ T* -0.0029 Tc -0.0021 Tw [(ac)-7.1(t)5.7(e)-5.1(d o)12(r)-0.3( is ac)-7.1(tin)7.7(g)-3.2(. 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188.624 450.319 188.922 451.881 c 189.219 453.441 191.274 465.164 192.269 465.263 c 193.757 465.413 195.764 449.946 196.582 449.946 c 197.4 449.946 200.227 450.616 200.598 451.657 c 200.97 452.699 202.766 465.441 204.02 465.71 c 205.06 465.933 207.441 450.171 208.11 450.245 c 208.779 450.319 212.051 450.021 212.423 451.212 c 212.795 452.4 214.843 465.253 215.696 465.413 c 216.885 465.636 219.414 449.724 220.009 449.65 c 223.132 448.98 223.654 450.319 v 224.175 451.657 226.475 464.224 227.371 464.224 c 229.232 464.224 230.05 450.02 231.241 450.17 c 232.43 450.319 234.959 449.872 235.479 451.136 c 235.998 452.4 237.696 464.522 239.121 464.297 c 240.537 464.074 242.47 449.427 243.288 449.724 c 244.105 450.02 247.898 451.359 248.047 452.996 c 248.196 454.631 249.934 463.432 250.725 463.479 c 251.914 463.554 253.923 450.394 254.592 450.319 c 255.261 450.243 259.202 449.946 259.502 451.805 c 259.799 453.665 261.431 463.703 262.326 463.703 c 264.111 463.703 265.079 451.284 265.748 450.913 c 268.873 448.832 269.764 450.17 v 270.657 451.509 272.591 463.033 274.301 463.107 c 275.359 463.154 277.35 449.873 278.243 450.17 c 279.134 450.467 282.333 450.467 282.408 451.509 c 282.482 452.549 284.963 462.815 285.754 462.959 c 287.391 463.257 289.101 450.319 289.77 450.393 c 290.44 450.467 293.118 449.204 293.712 450.393 c 294.308 451.583 296.553 463.067 297.357 463.033 c 299.141 462.959 301 450.245 301.595 450.096 c 302.19 449.946 305.016 450.096 305.538 450.989 c 306.058 451.881 308.1 461.804 308.957 462.066 c 311.007 462.69 312.473 449.277 312.9 449.277 c 315.726 449.204 m 317.956 450.021 320.041 463.479 320.782 462.587 c 321.528 461.695 323.461 450.096 324.205 449.946 c 324.948 449.799 328.592 449.427 328.965 450.542 c 329.336 451.657 331.696 463.772 332.385 463.925 c 333.723 464.224 335.732 450.467 336.402 450.393 c 337.072 450.319 352.465 449.277 352.836 450.17 c 353.21 451.062 355.514 465.562 356.334 464.968 c 357.151 464.371 359.827 449.277 360.645 449.501 c 361.464 449.724 365.109 450.541 365.777 456.193 c 366.447 461.844 367.06 466.542 367.786 466.38 c 369.125 466.081 370.984 450.989 371.431 450.914 c 371.876 450.84 375.299 449.798 375.819 450.84 c 376.339 451.881 377.976 463.925 379.239 463.851 c 380.595 463.771 382.363 450.393 383.032 450.467 c 383.701 450.542 386.602 449.351 387.42 450.69 c 388.238 452.028 389.652 463.851 390.544 463.404 c 391.436 462.959 394.189 450.02 394.858 450.243 c 395.527 450.467 399.84 452.996 400.213 455.524 c 400.584 458.051 401.612 463.812 402.444 463.851 c 404.08 463.925 405.715 450.616 407.054 451.062 c 408.393 451.509 422.376 449.351 423.342 450.393 c 424.31 451.434 424.979 457.085 425.424 458.498 c 425.871 459.91 426.17 463.554 426.839 462.81 c 427.507 462.067 429.069 455.524 429.516 455.896 c 429.962 456.268 431.97 471.362 432.64 470.543 c 433.307 469.724 436.209 452.104 437.324 452.476 c 438.44 452.847 439.852 452.104 440.225 452.253 c 440.597 452.4 441.788 457.01 441.714 459.687 c 441.638 462.364 443.273 482.662 443.869 482.291 c 444.465 481.92 445.952 472.848 446.101 472.179 c 446.249 471.51 447.439 452.772 448.481 452.549 c 449.521 452.327 449.671 452.921 450.412 453.516 c 451.157 454.111 451.902 454.335 453.017 453.592 c 454.133 452.847 454.801 452.922 455.843 452.476 c 456.883 452.029 457.33 451.879 458.148 452.178 c 458.966 452.476 459.786 454.705 459.934 456.193 c 460.081 457.68 461.645 487.72 462.464 486.901 c 463.279 486.083 465.06 465.412 465.214 464.595 c 465.436 463.406 465.364 461.768 466.404 462.364 c 467.443 462.96 467.818 467.494 468.338 466.677 c 468.858 465.859 469.304 459.912 470.049 460.06 c S 0 0 0 0.84999 K [0.8343 0.8343 ]0 d 88.37 452.959 m 89.932 452.848 89.822 453.628 91.047 453.294 c 92.275 452.959 92.944 451.398 93.838 452.959 c 95.733 454.52 95.721 496.458 97.184 495.787 c 98.559 495.156 98.408 493.327 98.857 488.612 c 100.018 476.449 100.246 453.623 101.869 452.624 c 103.319 451.732 103.174 454.355 104.435 453.851 c 104.992 453.628 105.551 452.067 106.22 452.513 c 108.228 453.851 108.378 495.453 110.124 495.898 c 111.749 496.313 111.506 490.269 111.798 482.961 c 112.272 471.096 112.223 454.61 114.363 453.851 c 114.921 453.517 115.591 454.631 v 116.26 455.747 116.148 456.973 117.153 456.082 c 118.157 455.189 118.379 453.963 119.607 453.851 c 120.834 453.739 120.834 452.959 122.73 452.736 c 124.627 452.513 126.859 454.631 127.974 455.301 c 129.089 455.97 129.759 453.405 131.32 452.736 c 132.882 452.067 136.675 451.398 137.233 453.182 c 137.791 454.967 138.125 457.085 139.019 456.194 c 139.91 455.301 140.914 452.736 142.031 452.624 c 143.145 452.513 147.384 452.179 148.723 452.848 c 150.062 453.517 149.95 454.409 151.958 453.851 c 153.967 453.294 153.855 452.959 155.194 452.736 c 156.533 452.513 159.99 453.294 160.995 453.517 c 161.999 453.739 161.854 454.009 163.561 453.07 c 165.793 451.843 171.593 451.843 172.597 452.848 c 173.601 453.851 174.381 454.743 176.278 453.405 c 178.174 452.067 182.972 451.62 184.199 452.959 c 185.426 454.297 185.426 455.301 187.211 453.851 c 188.997 452.401 189.554 451.843 191.116 452.179 c 192.678 452.513 193.123 451.509 195.242 452.848 c 197.363 454.186 197.587 455.413 199.371 453.851 c 201.155 452.289 199.371 452.067 201.267 452.289 c 203.164 452.513 206.288 451.843 207.403 452.959 c 208.519 454.075 208.965 455.078 210.638 453.739 c 212.311 452.401 213.428 452.624 215.435 452.401 c 217.443 452.179 218.224 451.732 219.563 453.07 c 220.901 454.409 220.901 455.524 222.017 454.52 c 223.132 453.517 223.914 452.179 225.141 452.179 c 226.368 452.179 233.061 452.067 234.178 452.624 c 235.292 453.182 235.563 453.828 237.524 452.848 c 239.533 451.843 240.759 452.289 242.544 453.517 c 244.329 454.743 244.887 455.524 246.225 454.186 c 247.565 452.848 246.559 452.513 250.241 452.289 c 253.923 452.067 253.923 452.848 255.373 453.405 c 256.822 453.963 256.488 453.739 259.277 453.07 c 262.067 452.401 263.295 451.62 264.521 452.401 c 265.748 453.182 266.418 454.409 268.426 453.739 c 270.786 452.953 270.823 452.586 272.107 452.289 c 273.557 451.955 277.35 452.067 278.243 452.959 c 279.134 453.851 278.911 454.855 279.915 454.52 c 280.921 454.186 281.589 452.736 283.151 452.401 c 284.713 452.067 287.948 451.955 289.064 452.848 c 290.178 453.739 291.518 454.075 292.856 453.739 c 294.194 453.405 293.302 451.955 296.203 452.289 c 299.103 452.624 300.109 451.955 301.447 452.959 c 302.786 453.963 302.34 454.52 303.565 453.739 c 304.794 452.959 303.901 452.289 307.359 452.513 c 310.388 452.708 308.043 452.624 310.259 452.624 c 312.044 452.624 311.487 453.07 313.605 453.628 c 315.726 454.186 314.052 452.736 317.623 452.401 c 321.193 452.067 323.089 451.955 324.205 452.624 c 325.452 453.373 325.207 454.967 326.771 454.186 c 328.332 453.405 327.552 452.624 329.56 452.513 c 331.566 452.401 334.244 452.067 335.249 452.624 c 336.251 453.182 335.919 453.963 336.811 453.517 c 337.702 453.07 337.925 452.289 339.264 452.179 c 340.604 452.067 343.504 451.955 344.62 452.959 c 345.734 453.963 345.696 454.783 347.074 453.405 c 348.3 452.179 347.855 452.624 349.417 453.739 c 350.979 454.855 349.973 454.297 352.65 453.405 c 355.33 452.513 357.559 451.62 359.121 452.513 c 360.683 453.405 360.683 454.631 361.912 454.186 c 363.138 453.739 361.459 452.289 365.369 452.289 c 369.162 452.289 369.831 452.067 370.724 452.736 c 371.617 453.405 371.728 454.186 374.182 453.405 c 376.636 452.624 377.528 452.179 379.424 452.179 c 381.322 452.179 381.769 453.07 382.996 453.739 c 384.222 454.409 384.111 455.747 385.675 453.739 c 386.592 452.558 389.913 451.843 391.697 452.624 c 393.481 453.405 393.147 454.297 395.378 453.851 c 397.609 453.405 395.489 452.179 399.283 452.401 c 403.076 452.624 403.856 451.398 404.525 453.182 c 405.605 456.056 406.646 467.681 407.985 466.121 c 409.323 464.558 409.88 453.517 411.443 452.959 c 413.004 452.401 411.554 453.628 414.344 452.959 c 417.132 452.289 418.359 452.401 421.706 452.289 c 425.054 452.179 434.202 452.067 434.535 452.624 c 435.397 454.059 436.878 468.797 437.882 467.459 c 438.885 466.121 440.672 453.851 442.121 453.07 c 443.572 452.289 443.795 451.62 445.133 452.401 c 446.473 453.182 446.694 451.955 447.252 454.631 c 447.81 457.308 449.038 472.812 450.041 471.139 c 451.047 469.466 452.719 454.52 453.835 455.635 c 454.951 456.752 455.955 462.216 456.735 461.1 c 457.517 459.985 459.19 452.624 461.086 452.513 c 462.983 452.401 470.234 452.401 y S Q q 1 i 473.432 660.634 -403.073 -420.887 re 70.359 660.634 m W n 87 525.448 387 -286.883 re 294 402.015 m W* n 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n 0 0 0 1 K 0 J 0 j 0.417 w 4 M []0 d /GS5 gs 87.255 452.179 m 470.569 452.179 l S /GS4 gs BT /F16 1 Tf 8.344 0 0 8.342 88.3899 519.5978 Tm /Cs8 cs 1 scn 0 Tc 0 Tw (A.)Tj -0.1099 -15.8008 TD -0.013 Tc (B.)Tj ET EMC Q q 1 i 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n 1 g /GS2 gs 87 696 387 12 re f BT /F6 1 Tf 10 0 0 10 87 700.7319 Tm 0.017 g 0 Tc 0 Tw (26)Tj /F8 1 Tf 11.0033 0 TD 0.1514 Tc -0.0003 Tw ( 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va)15.3(r)-9.6(i)3.4(a)15.3(n)21.4(ts: r)18.3(e)3.4(pe)5.4(a)21.4(t)-0.7( n)16.3(u)12.4(m)17.4(b)3.5(er)]TJ -1.1378 -1.1818 TD -0.0084 Tc 0.0084 Tw [(pol)7(y)-21.2(mor)-29.4(p)1.8(h)8.7(i)-12.3(sm)-8.3(s)-8.3( a)7.7(n)-1.3(d)-8.2( cop)4.9(y)-8.3( n)8.7(u)4.8(m)9.8(b)-4.1(e)-8.3(r)-8.4( pol)7(y)-21.2(mor)-29.4(p)1.8(h)8.7(i)-12.3(sm)-8.3(s)]TJ /F6 1 Tf -5.9794 -1.1818 TD 0.0026 Tc -0.0076 Tw [(I)16.2(n)0.1( addi)12.3(tio)12.4(n)0.1( t)6.1(o)0.2( va)9(r)-5.8(i)-2.8(a)8(b)12.4(ili)12.3(t)-2.9(y a)9(r)-5.8(isin)8.1(g f)-9.7(r)13.3(o)12.4(m)0.1( )36.1(p)-8.8(o)12.4(i)0.1(n)19.1(t)0( m)19.2(u)12.2(t)-5.8(a)19(tio)12.4(n)8.1(s,)138.4( ma)9(n)23.3(y)0( o)12.4(r)8.2(ga)9(nism)8.2(s als)-7.8(o)]TJ T* 0.0015 Tc -0.0065 Tw [(ha)17.8(v)7.9(e)-0.1( lo)-8.8(ci wi)12.1(t)-6(h)-0.2( hig)-6.9(h)-5.1(l)6.9(y)-0.2( va)8.8(r)-6(i)-3(a)7.8(b)7(le n)18.9(u)-0.3(m)9.9(b)-8.9(er)6(s o)12.2(f)-0.2( co)11.2(p)12(ies o)12.2(f)-0.2( mem)9.9(b)-8.9(er)6(s o)12.2(f)-0.2( )]TJ /F3 1 Tf 25.42 0 TD -0.0064 Tw [(t)10(a)16(n)7(d)4.2(em a)16(r)-8.9(r)18.9(a)23.1(ys)]TJ /F6 1 Tf -25.42 -1.1818 TD -0.0049 Tc -0.031 Tw [(o)12.3(f)0( r)13.2(e)0.1(p)-8.8(e)-5.8(a)19(t)6.1(ed s)-7.9(e)-4.8(q)9.9(u)-0.1(ences \()]TJ /F1 1 Tf 9.0573 0 TD -0.0132 Tc 0 Tw [(Fi)-8.1(g)-11.1(u)-8.1(re)-190.2(1)-8.2(.)-8.1(9)]TJ /F6 1 Tf 4.1143 0 TD -0.0047 Tc -0.0312 Tw [(\). Ther)13.4(e a)9.2(r)13.4(e tw)8.3(o s)5.3(u)0.1(c)6.3(h)0.2( typ)-8.6(e)0.3(s o)12.5(f)0.2( va)9.2(r)-5.6(i)-2.7(a)8.2(b)7.4(le r)13.4(e)0.3(p)-8.6(e)-5.6(a)19.2(ts:)]TJ /F3 1 Tf -13.1716 -1.1818 TD -0.0126 Tc 0 Tw [(mi)-13.2(c)-17.2(r)1.7(o)-11.2(s)-20.2(at)-7.2(el)-12(lit)-7.2(e)-9.2(s)]TJ /F6 1 Tf 5.804 0 TD -0.0019 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.7642 0 TD -0.0107 Tc [(mini)-19.3(s)-18.3(a)6.8(t)-5.3(e)0.7(l)-10.1(l)-2.1(it)-5.3(e)-7.3(s)]TJ /F6 1 Tf 5.1401 0 TD 0.0042 Tc 0.0181 Tw [(. 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det)5.8(er)-6.1(minin)7.8(g)-0.2( t)-6.2(h)3.8(e sum o)12(f)-0.3( t)-6.2(h)3.8(e n)18.8(u)-0.4(m)9.8(b)-9(er)5.9(s o)12(f)-0.3( dif)-10.1(f)8.7(e)-0.2(r)12.9(e)-0.2(nces b)-9(e)-0.2(tw)7.8(een a)-5.3(l)-5.2(l p)-9.1(o)-0.2(ssib)6.9(le)]TJ T* 0.005 Tc 0.056 Tw [(pa)9.3(ir)6.4(s o)12.6(f)0.3( a)-4.7(l)-4.6(leles a)9.3(n)4.5(d t)-5.6(h)4.4(en di)7.5(vidin)8.4(g b)16.5(y)0.2( t)-5.6(h)4.4(e n)19.4(u)0.2(m)10.4(b)-8.4(er o)12.6(f)0.3( s)-7.6(e)-4.5(q)10.2(u)0.2(ence pa)9.3(ir)6.4(s t)-5.6(h)3.4(a)19.3(t)]TJ T* -0.004 Tc -0.01 Tw [(w)9(e)1(r)14.1(e)1( co)13.2(m)20(p)-4(a)9.9(r)14.1(ed [wi)13.2(t)-5(h )]TJ /F3 1 Tf 8.5687 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.6782 0 TD -0.0051 Tc -0.0089 Tw [(indep)-9(enden)18.9(t a)-5.2(l)-5.1(leles, t)-6.1(h)-0.2(is eq)9.7(ua)-5.2(ls )]TJ /F3 1 Tf 12.4109 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.4652 0 TD (\()Tj /F3 1 Tf 0.3411 0 TD (k)Tj /F6 1 Tf 0.6782 0 TD -0.0049 Tc -0.0091 Tw [( 1\)/2], a)9(n)4.2(d b)16.2(y)]TJ -23.1424 -1.1818 TD 0.0045 Tc 0.0652 Tw [(t)-6.1(h)3.9(e n)18.9(u)-0.3(m)9.9(b)-8.9(er o)12.1(f)-0.2( bas)-8.1(e)-0.1(s st)9.8(udied)6(.)-0.1( I)16(n)-0.2( t)-6.1(h)3.9(e exa)8.8(m)18.9(p)6.8(l)-0.2(e f)-10(r)13(o)12.1(m)-0.2( )]TJ /F1 1 Tf 20.8167 0 TD -0.0032 Tc 0.0694 Tw [(Fi)-8.1(g)-11.1(u)-8.1(re)-8( 1)-8.2(.)-8.1(8)]TJ /F6 1 Tf 4.602 0 TD 0 Tc 0 Tw (\()Tj /F1 1 Tf 0.3507 0 TD 0.0173 Tc [(Sec)6.6(t)17.6(i)6.5(o)22.4(n)]TJ -25.7695 -1.1818 TD -0.0019 Tc (1.2.iii.b)Tj /F6 1 Tf 3.1641 0 TD -0.0014 Tc -0.0036 Tw [(\), t)-5.8(h)4.2(e las)5.2(t)0.1( t)-5.8(h)0.1(r)13.3(e)-4.7(e alleles, la)8.1(b)-8.6(e)4.3(led B)17.2(,)0.2( A)44.3()0.2( a)9.1(n)4.3(d A+, a)9.1(r)13.3(e 5022 bas)-7.8(e)0.2(s lo)12.4(n)8.2(g)-2.7(.)]TJ -3.1641 -1.1818 TD 0.0048 Tc 0.021 Tw [(Of t)-5.8(h)4.2(es)-7.8(e)6.3(,)0.2( t)-5.8(h)4.2(e B a)-4.9(l)-4.8(lele dif)-9.7(f)9.1(e)0.2(r)6.2(s)0.1( a)19.1(t)0.1( s)-7.8(e)-7.6(v)8.2(e)0.2(n n)19.2(u)0(c)6.2(l)0.1(eo)11.5(tide si)12.4(t)6.2(e)0.2(s f)-9.7(r)13.3(o)12.4(m)0.1( t)-5.8(h)4.2(e A)44.3()0.2( a)-4.9(l)-4.8(lele)6.3(,)]TJ T* 0.0025 Tc -0.0075 Tw [(a)9.2(n)4.4(d a)19.2(t)0.2( f)9.3(o)11.6(ur \(dif)-9.5(f)9.3(e)0.3(r)13.5(e)0.3(n)19.3(t\) si)12.5(t)6.3(e)0.3(s f)-9.5(r)13.5(o)12.6(m)0.3( t)-5.6(h)4.4(e A+ allele)6.4(,)0.4( a)9.2(n)4.4(d t)-5.6(h)4.4(e A)44.4()0.4( a)9.2(n)4.4(d A+ alleles)]TJ T* -0.0013 Tc -0.0037 Tw [(dif)-9.8(f)9(e)0.1(r a)18.9(t)-0.1( t)-5.9(h)-0.1(r)13.2(e)-4.8(e si)12.2(t)6(e)0.1(s. The sum o)12.3(f)0( t)-5.9(h)4.1(e pa)8.9(ir)-28.8(wis)-7.9(e)0.1( dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(nces b)-8.7(e)0.1(tw)8.1(een all t)-5.9(h)-0.1(r)13.2(e)-4.8(e)]TJ T* 0.0041 Tc 0.0001 Tw [(co)11.7(m)9.5(b)11.7(ina)18.4(t)-5.5(io)11.7(n)7.5(s)-0.6( o)11.7(f)-0.6( s)-8.5(e)-5.4(q)9.3(u)-0.7(ences is 7 + 3 + 4 = 14, s)-8.5(o)-0.5( t)-6.5(h)2.5(a)18.4(t)-0.6( t)-6.5(h)3.5(e me)-6.4(a)8.4(n)-0.6( dif)-10.4(f)8.4(e)-0.5(r)12.6(e)-0.5(nce)]TJ T* -0.0046 Tc -0.0231 Tw [(p)-8.5(e)0.4(r si)12.6(t)6.4(e)0.4( p)-8.5(e)0.4(r allele pa)9.3(ir is j)10.3(u)3.4(s)5.4(t)0.3( under 0.1%:)]TJ /F7 1 Tf 10.1219 -2.0455 TD 0 Tc 0 Tw (p)Tj /F6 1 Tf 0.7432 0 TD -0.0049 Tc -0.0228 Tw (= 14/\(3 )Tj /F7 1 Tf 3.0664 0 TD 0 Tc 0 Tw ()Tj /F6 1 Tf 0.7432 0 TD -0.0048 Tc -0.0229 Tw (5022\) = 0.00093)Tj /F1 1 Tf -12.601 -2.5455 TD 0.0495 Tc 0 Tw (B1.3.ii.)Tj /F2 1 Tf 3.6198 0 TD -0.0886 Tc [(Wa)-80(t)-86.8(t)-91(e)-98.3(r)-93.1(s)-105.9(o)-87(n)-18()-6(s)-98.1( )]TJ /F7 1 Tf 4.8951 0 TD 0 Tc (q)Tj /F2 1 Tf 0.7655 0 TD (\()Tj /F7 1 Tf 0.3566 0 TD (q)Tj /F5 1 Tf 7.7 0 0 6.6 260.6572 479.8751 Tm (w)Tj /F2 1 Tf 11 0 0 11 265.9045 483.5051 Tm 0.0104 Tc -0.0009 Tw [(\) f)10.8(o)12(r a sa)9(m)17.8(p)7(le o)12(f)0.8( )]TJ /F5 1 Tf 6.8881 0 TD 0 Tc 0 Tw (k)Tj /F2 1 Tf 0.717 0 TD 0.009 Tc 0.0005 Tw [(D)9.6(N)38.5(A s)-8.3(e)-6.5(q)9.5(u)-0.6(ences)]TJ /F6 1 Tf -20.3237 -1.7727 TD 0.0035 Tc -0.0038 Tw [(Ano)10.2(t)-7.1(her wa)16.8(y t)4.9(o)-1.1( me)-7(asur)12(e di)6(v)6.9(e)-1.1(r)4.9(s)-1.2(i)11.1(t)-4.2(y w)6.9(o)10.2(u)-6.2(l)-1.2(d sim)17.9(p)5.8(l)5.8(y)-1.3( b)-9.9(e)-1.1( t)4.9(o)-1.1( co)10.2(un)17.9(t t)-7.1(h)2.9(e n)17.9(u)-1.3(m)8.9(b)-9.9(er)]TJ 0 -1.1818 TD 0.0018 Tc -0.0068 Tw [(o)11.9(f)-0.5( p)-9.3(o)6.7(l)6.6(y)-3.5(mo)11.9(r)-10.2(p)6.6(hic si)11.8(t)5.6(e)-0.4(s \(si)11.8(t)5.6(e)-0.4(s in t)-6.4(h)3.6(e s)-8.3(e)-5.3(q)9.5(u)-0.6(ence t)-6.4(h)2.7(a)18.5(t)-0.5( ha)17.5(v)7.6(e)-0.4( va)8.5(r)-6.3(i)-3.3(a)8.5(n)18.6(ts in t)-6.4(h)3.7(e s)-6.4(a)8.5(m-)]TJ T* 0.0043 Tc 0.0184 Tw [(p)6.6(l)-0.4(e\). This is s)-8.3(o)11.9(metimes deno)11(t)5.7(ed b)15.8(y)-0.5( )]TJ /F3 1 Tf 14.3166 0 TD 0 Tc 0 Tw (S)Tj 7.7 0 0 6.6 288.6804 434.3751 Tm (k)Tj /F6 1 Tf 11 0 0 11 292.3359 438.0051 Tm 0.0038 Tc 0.0189 Tw [(, a)8.1(n)3.3(d is us)-8.8(ed b)15.3(y)-1( h)18.1(u)-1(ma)8.1(n g)7.3(e)-0.8(neticists)]TJ -15.1214 -1.1818 TD -0.0052 Tc -0.0005 Tw [(\(in s)4.8(t)-6.2(a)18.7(t)5.8(emen)18.8(ts s)4.8(u)-0.4(c)5.8(h)-0.3( as )35.8(t)-3.3(w)7.8(o)-0.2( va)8.7(r)-6.1(i)-3.2(a)8.7(n)18.8(ts p)-9.1(e)-0.2(r kilo)5(bas)-8.2(e)57.9(\). This is c)5.8(l)-0.3(e)-6.1(a)8.7(rl)6.7(y un)7.8(s)-6.2(a)18.7(tis-)]TJ T* 0.0001 Tc -0.0051 Tw [(fac)-6.6(t)6.2(o)12.5(r)-28.6(y)73.1(, b)-8.6(e)-4.6(ca)19.1(us)-7.7(e t)-5.7(h)4.3(es)-7.7(e n)19.2(u)0(m)10.2(b)-8.6(er)6.3(s will b)-8.6(e)0.2( la)9.1(r)8.2(g)8.3(er in la)9.1(r)8.2(g)8.3(er s)-5.8(a)9.1(m)19.2(p)7.2(les. H)25.3(o)16.4(w)8.3(e)-7.6(v)8.2(e)0.2(r)63.4(,)]TJ T* 0.0052 Tc 0.2759 Tw [(s)5.6(u)0.4(c)6.6(h)0.5( co)11.9(un)19.6(ts ca)9.5(n b)-8.2(e)0.6( co)12.8(r)-5.3(r)13.7(ec)-6.3(t)6.6(e)-4.3(d t)6.6(o)0.6( t)-5.4(a)-4.5(k)9.6(e)0.6( in)19.6(t)6.6(o)0.6( acco)11.9(un)19.6(t t)-5.4(h)4.6(e n)19.6(u)0.4(m)10.6(b)-8.2(er o)12.8(f)]TJ T* 0.0044 Tc 0.0391 Tw [(s)-8.2(e)-5.1(q)9.6(u)-0.4(ences in t)-6.2(h)3.8(e s)-6.2(a)8.7(m)18.8(p)6.7(le)5.9(, )]TJ /F3 1 Tf 10.3004 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.4748 0 TD 0.0049 Tc 0.0386 Tw [(. This us)-7.7(es t)-5.7(h)4.3(e q)10.1(u)-2.8(a)9.2(n)19.3(ti)12.5(ty )]TJ /F3 1 Tf 9.7436 0 TD 0 Tc 0 Tw (a)Tj 7.7 0 0 6.6 357.1476 382.3751 Tm (k)Tj /F6 1 Tf 11 0 0 11 360.8032 386.0051 Tm 0.0052 Tc 0.0383 Tw [(, w)-6.3(h)0.5(ic)6.6(h is gi)7.7(v)8.6(e)0.6(n b)16.7(y)]TJ /F1 1 Tf -21.3457 -1.1818 TD -0.0039 Tc -0.023 Tw [(E)-16.5(q)12.4(ua)16.4(t)6.4(i)-4.7(o)11.2(n)1.2( B1.3.1)]TJ /F6 1 Tf 6.6131 0 TD 0 Tc 0 Tw (:)Tj /F3 1 Tf 2.4101 -2.0455 TD (a)Tj 7.7 0 0 6.6 230.5922 346.875 Tm (k)Tj /F6 1 Tf 11 0 0 11 236.3668 350.5051 Tm -0.0049 Tc -0.0228 Tw (= 1 + 1/2 + 1/3 + )Tj /F7 1 Tf 6.7234 0.2273 TD 0 Tc 0 Tw ()Tj /F6 1 Tf 1.1943 -0.2273 TD -0.005 Tc -0.0227 Tw (+ 1/\()Tj /F3 1 Tf 1.9167 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.6645 0 TD -0.0049 Tc -0.0228 Tw [( 1\))-3704.5(\(B1.3.1\))]TJ -20.5323 -2.0455 TD -0.0211 Tc 0 Tw [(If)-16.2( )]TJ /F3 1 Tf 0.8103 0 TD 0 Tc (k)Tj /F6 1 Tf 0.6645 0 TD -0.0092 Tc -0.0185 Tw [(is l)-7.3(a)4.7(rge, )]TJ /F3 1 Tf 3.1467 0 TD 0 Tc 0 Tw (a)Tj 7.7 0 0 6.6 182.1743 324.375 Tm (k)Tj /F6 1 Tf 11 0 0 11 187.9489 328.0051 Tm -0.0047 Tc -0.023 Tw [(is a)19.2(p)11.4(p)12.4(r)13.4(o)16.4(x)0.2(ima)19.2(t)6.3(el)7.2(y eq)10.1(ual t)6.3(o)0.3( ln\()]TJ /F3 1 Tf 11.12 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.4652 0 TD -0.005 Tc -0.0227 Tw [(\), t)-6(h)4(e na)18.9(t)9.9(u)-0.2(ral loga)8.9(r)-5.9(i)12.2(t)-6(hm o)12.2(f)-0.1( )]TJ /F3 1 Tf 10.3324 0 TD 0 Tc 0 Tw (k)Tj /F6 1 Tf 0.4652 0 TD (.)Tj -26.9236 -1.1818 TD 0.0024 Tc [(W)12.1(h)4.1(en )]TJ /F3 1 Tf 2.6925 0 TD 0 Tc (S)Tj 7.7 0 0 6.6 172.7906 311.3751 Tm (k)Tj /F6 1 Tf 11 0 0 11 178.8711 315.0051 Tm 0.0027 Tc -0.0077 Tw [(is di)7.4(vided b)16.4(y)0.2( t)-5.7(h)4.4(e )83.2(c)0.3(o)12.6(r)-5.6(r)13.5(e)-4.6(c)-6.6(t)-4.7(io)12.6(n fac)-6.6(t)6.3(o)12.6(r)12.5()0.3( )]TJ /F3 1 Tf 14.441 0 TD 0 Tc 0 Tw (a)Tj 7.7 0 0 6.6 343.1394 311.3751 Tm (k)Tj /F6 1 Tf 11 0 0 11 349.2199 315.0051 Tm 0.0024 Tc -0.0074 Tw [(a)8.9(n)4.1(d b)16.1(y)-0.1( t)-6(h)4.1(e n)19(u)-0.2(m)10(b)-8.8(er o)12.3(f)]TJ -20.2927 -1.1818 TD 0.0048 Tc 0.1377 Tw [(bas)-7.8(e)0.2(s in t)-5.8(h)4.2(e s)-7.8(e)-4.7(q)10(u)0(ence \(t)6.2(o g)8.3(e)0.2(t a p)-8.7(e)0.2(r n)19.2(u)0(c)6.2(l)0.1(eo)11.5(tide di)7.3(v)8.2(e)0.2(r)6.2(s)0.1(i)12.4(t)-2.9(y estima)19.1(t)6.2(e)0.2(\), w)8.2(e)]TJ T* 0.0009 Tc -0.0059 Tw [(o)7.8(b)13.8(ta)11.5(in th)6.6(e s)7.6(t)-3.4(a)21.5(t)-2.4(i)5.8(s)7.6(tic called )]TJ /F3 1 Tf 10.0412 0 TD -0.0013 Tc 0 Tw [(W)93.2(a)22.4(tt)10.3(erso)10.2(n)92.3()89.4(s)]TJ /F7 1 Tf 4.5962 0 TD 0 Tc (q)Tj /F6 1 Tf 0.5194 0 TD -0.0017 Tc -0.0033 Tw [(, o)12.2(r)0( )]TJ /F7 1 Tf 1.5357 0 TD 0 Tc 0 Tw (q)Tj /F3 1 Tf 7.7 0 0 6.6 315.3322 285.3751 Tm (w)Tj /F6 1 Tf 11 0 0 11 320.4792 289.005 Tm -0.0014 Tc -0.0036 Tw [(. I)16.4(f)0.2( t)-5.7(h)4.3(e p)-8.6(o)11.6(p)11.4(u)-4.8(la)19.2(tio)12.5(n)0.2( is a)19.2(t)0.2( eq)10.1(ui-)]TJ -17.6799 -1.1818 TD 0.0044 Tc 0.2174 Tw [(lib)12(r)-6.1(i)12(u)-0.4(m, a)8.7(n)3.9(d t)-6.2(h)3.8(er)12.9(e is no s)-8.2(e)3.9(lec)-7.1(t)-5.2(io)12(n o)12(n)-0.3( t)-6.2(h)3.8(e va)8.7(r)-6.1(i)-3.2(a)8.7(n)18.8(ts a)18.7(t)-0.3( t)-6.2(h)-0.3(is lo)-9(c)-7.1(u)2.8(s, t)-6.2(h)3.8(e)]TJ T* 0.0053 Tc 0.015 Tw [(exp)-8.2(e)-4.2(c)-6.2(t)6.7(ed va)-4.4(l)12.8(u)0.5(e o)12.9(f)0.6( )]TJ /F7 1 Tf 7.2559 0 TD 0 Tc 0 Tw (q)Tj /F3 1 Tf 7.7 0 0 6.6 211.6007 259.3751 Tm (w)Tj /F6 1 Tf 11 0 0 11 219.5161 263.0051 Tm 0.0046 Tc (= )Tj /F3 1 Tf 0.8319 0 TD 0 Tc (S)Tj 7.7 0 0 6.6 233.8655 259.3751 Tm (k)Tj /F6 1 Tf 11 0 0 11 237.521 263.0051 Tm (/)Tj /F3 1 Tf 0.3356 0 TD (a)Tj 7.7 0 0 6.6 246.6552 259.3751 Tm (k)Tj /F6 1 Tf 11 0 0 11 253.031 263.0051 Tm 0.0106 Tc 0.0097 Tw [(i)9.1(s)5.9( th)10(e)6( sa)14.9(m)10.1(e)6( a)9(s)5.9( th)9(a)24.9(t)5.9( o)18.2(f)5.9( )]TJ /F7 1 Tf 8.6673 0 TD 0 Tc 0 Tw (p)Tj /F6 1 Tf 0.8011 0 TD 0.0038 Tc 0.0165 Tw [(\(t)-6.8(he basis f)8.1(o)11.4(r t)-6.8(h)-0.9(is is)]TJ -21.0167 -1.1818 TD 0.0053 Tc 0.0636 Tw [(der)-5.2(i)7.8(v)8.7(ed in )]TJ /F1 1 Tf 4.4522 0 TD 0.0046 Tc 0.0608 Tw [(S)-12.3(e)-13.1(c)-6.1(t)4.9(i)-6.2(o)9.7(n 5.1.iii.c)]TJ /F6 1 Tf 6.5373 0 TD 0.0034 Tc 0.0655 Tw [(, b)10(u)10.8(t her)11.9(e)-1.2( w)6.8(e)-1.2( sim)17.8(p)5.7(l)5.7(y)-1.4( st)-7.2(a)17.7(t)4.8(e t)-7.2(h)2.8(e r)11.9(e)-1.2(su)-6.3(l)10.9(t)-1.3(\). 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-30.5421 -1.1818 TD -0.0048 Tc (0.02 )Tj /F7 1 Tf 1.8691 0 TD 0 Tc ()Tj /F6 1 Tf 0.7643 0 TD -0.0048 Tc -0.0017 Tw [(ln\(100\), i)6.3(.)0.2(e)6.3(., a)8.1(b)-8.6(o)11.5(u)12.2(t 82,893, o)12.4(r)0.1( 2% o)12.4(f)0.1( t)-5.8(h)4.2(e t)6.2(o)11.5(t)-5.8(a)-4.9(l n)19.2(u)0(m)10.2(b)-8.6(er o)12.4(f)0.1( si)12.4(t)6.2(e)0.2(s. S)6.2(i)0.2(mila)9.1(r cal-)]TJ -2.6334 -1.1818 TD -0.0051 Tc -0.0019 Tw [(c)-7(u)-5.2(la)18.8(tio)12.1(n)7.9(s sho)16(w t)-6.1(h)2.9(a)18.8(t)-0.2( s)-8.1(e)-7.9(v)7.9(e)-0.1(ra)-5.2(l millio)12.1(n S)12(N)-0.2(P)27.8(s)-0.2( a)8.8(r)13(e p)12(r)13(es)-8.1(en)18.9(t g)8(e)-0.1(no)12.1(me wide in t)-6.1(h)3.9(e p)-9(o)11.2(p)11(u)-0.3(-)]TJ T* -0.005 Tc -0.0227 Tw [(la)18.9(tio)12.2(n)8(s o)12.2(f)-0.1( mos)5(t)-0.1( m)19(u)-5.1(l)12.1(t)-5(icell)12.1(u)-5.1(la)8.9(r o)12.2(r)8(ga)8.9(nism)8(s, w)-6.9(h)-0.1(ic)6(h ha)17.9(v)8(e)0( m)19(u)-0.2(c)6(h)-0.1( la)8.9(r)8(g)8.1(er g)8.1(e)0(no)12.2(mes.)]TJ /F1 1 Tf 11.8796 -2.8636 TD 0.05 Tc 0 Tw [(1.2.v)75.4(.)]TJ /F2 1 Tf 2.6858 0 TD -0.0137 Tc [(Ha)-5.1(p)-17.1(l)-23.2(o)-13.3(t)-23.1(y)-23.3(p)-33(e)-23.4(s)]TJ /F1 1 Tf -9.1717 -1.7727 TD 0.0499 Tc [(1.2.v)75.3(.)0(a.)]TJ /F3 1 Tf 3.5001 0 TD -0.0131 Tc 0.0131 Tw [(D)-19.7(e)-13(f)-20.9(i)0.1(niti)-8.9(on)-13.1( an)-6(d)-12.9( u)-17(s)-15.9(e)-13( in)-13.1( m)-5.9(e)-6.9(a)-13.1(s)-3(ur)-21.9(ing)-13( v)-8.7(a)3(r)-21.9(i)-8.9(a)9.1(b)-2.9(i)-7.9(l)0.3(it)-13(y)]TJ /F6 1 Tf -8.8938 -1.1818 TD -0.0017 Tc -0.0033 Tw [(The n)18.4(u)-0.8(m)9.4(b)-9.4(er o)11.7(f)-0.7( distinc)-7.4(t)-0.7( alleles p)-9.5(o)-0.5(ssib)6.5(le a)18.3(t)-0.7( a gi)6.5(v)7.4(en lo)-9.3(c)-7.4(u)2.4(s \(a def)-10.4(ined r)12.6(e)-0.6(gio)11.7(n)-0.6( o)11.7(f)-0.7( t)-6.6(h)3.5(e)]TJ T* 0.0045 Tc 0.1303 Tw [(g)8(e)-0.1(no)12.1(me\) dep)-9(ends o)12.1(n)-0.2( t)-6.1(h)3.9(e n)18.9(u)-0.3(m)9.9(b)-8.9(er o)12.1(f)-0.2( va)8.8(r)-6(i)-3.1(a)8.8(n)18.9(ts a)18.8(t)-0.2( e)-6(a)-0.3(c)5.9(h)-0.2( n)18.9(u)-0.3(c)5.9(l)-0.2(eo)11.2(tide si)12.1(t)5.9(e)-0.1( in t)-6.1(h)3.9(e)]TJ T* -0.0003 Tc -0.0047 Tw [(str)12.6(e)-0.5(t)5.5(c)5.6(h o)11.7(f)-0.6( g)7.6(e)-0.5(no)11.7(me t)-6.5(h)2.5(a)18.4(t)-0.6( has b)-9.3(e)-5.4(en s)-8.5(e)-5.4(q)9.3(u)-0.7(enced m)18.5(u)-5.6(l)11.6(t)-5.5(i)11.7(p)6.5(le times, a)8.4(n)3.6(d o)11.7(n)-0.6( t)-6.5(h)3.5(e n)18.5(u)-0.7(m)9.5(b)-9.3(er)]TJ T* 0.0019 Tc -0.0069 Tw [(o)12.6(f)0.3( co)12.6(m)10.3(b)12.6(ina)19.2(t)-4.7(io)12.6(n)8.3(s)0.2( o)12.6(f)0.3( t)-5.6(h)4.4(es)-7.6(e dif)-9.5(f)9.3(e)0.4(r)13.5(e)0.4(n)19.3(t)0.2( va)9.2(r)-5.5(i)-2.6(a)9.2(n)19.3(ts. I)16.5(n)0.3( a s)-5.6(a)9.2(m)19.4(p)7.3(le f)-9.5(r)13.5(o)12.6(m)0.3( a p)-8.6(o)11.6(p)11.5(u)-4.7(la)19.2(tio)12.6(n)0.3(, t)-5.6(h)4.4(e)]TJ T* -0.011 Tc 0 Tw [(te)-6(r)-11.9(m)-6.1( )]TJ /F3 1 Tf 2.1075 0 TD -0.013 Tc [(haplo)4(t)-8.1(y)-21.1(p)-3.9(e)]TJ /F6 1 Tf 3.9689 0 TD -0.0046 Tc -0.0149 Tw [(is co)12.6(mmo)12.6(n)-4.6(l)7.3(y)0.2( us)-7.6(ed t)6.4(o)0.4( r)13.5(e)0.4(f)9.3(e)0.4(r t)6.4(o)0.4( a s)-7.6(e)-4.5(q)10.2(u)0.2(ence t)-5.6(h)3.4(a)19.3(t)0.3( ca)9.3(r)-5.5(r)-5.5(ies a pa)9.3(r)-9.4(t)-4.6(ic)-6.5(ula)9.3(r)]TJ -6.0764 -1.1818 TD -0.0049 Tc -0.0222 Tw [(s)-7.9(e)0.1(t o)12.3(f)0( va)9(r)-5.8(i)-2.9(a)9(n)19.1(ts \()]TJ /F1 1 Tf 5.9464 0 TD -0.0046 Tc 0 Tw [(F)8.5(i)0.5(gur)8.6(e)-190.1(1.11)]TJ /F6 1 Tf 4.6178 0 TD -0.005 Tc -0.0221 Tw [(\), a)8.9(n)4.1(d a s)-6(a)8.9(m)19(p)7(le ca)8.9(n b)-8.8(e)0( des)-8(cr)-5.9(ib)-8.8(ed b)16.1(y)-0.2( listin)8(g t)-6(h)4(e dif)-9.9(f)8.9(er-)]TJ -10.5642 -1.1818 TD 0.0045 Tc 0.0235 Tw [(en)18.9(t ha)18.8(p)6.8(l)-0.2(o)11.2(t)-3.2(yp)-9(es t)-6.1(h)2.9(a)18.8(t)-0.2( i)12.1(t)-0.2( co)12.1(n)18.9(t)-6.1(a)8.8(i)-0.1(n)7.9(s)-0.2(, a)8.8(n)4(d t)-6.1(h)3.9(eir f)-10(r)13(eq)9.7(uencies. E)-13.1(a)-0.3(c)5.9(h)-0.2( si)12.1(t)5.9(e)-0.1( in a s)-8.1(e)-5(q)9.7(u)-0.3(ence)]TJ ET 1 g 114 696 387 12 re f BT 10 0 0 10 203.5202 700.7319 Tm 0.017 g 0.1439 Tc 0.2531 Tw (1.2 | )Tj /F8 1 Tf 3.2746 0 TD 0.151 Tc 0.0001 Tw [( )-12.1( )88.9(\015\015\015)-15.1()]TJ /F6 1 Tf 25.5134 0 TD 0 Tc 0 Tw (31)Tj ET /Document /MC11 BDC Q /GS3 gs BT /F6 1 Tf 9.826 0 0 9.826 114 363.6195 Tm /Cs8 cs 1 scn -0.0205 Tc 0 Tw [(Pa)-11.5(r)-7.5(e)-20.5(nt)-26.5(a)-25.5(l)]TJ 0 -1 TD -0.0004 Tc 0.0004 Tw [(co)11.6(m)9.6(b)11.6(ina)18.6(t)-5.4(io)11.6(n)7.6(s)-0.4( o)11.6(f)]TJ T* 0.0008 Tc -0.0008 Tw [(tw)8.8(o va)9.8(r)-5.2(i)-2.2(a)9.8(n)19.8(ts)]TJ 12.988 -3.1836 TD 0.0011 Tc -0.0011 Tw [(Reco)13.1(m)11.1(b)13.1(ina)20.1(t)-3.9(io)13.1(n b)-7.8(e)1.1(tw)9.1(een)]TJ 0.0575 -1 TD 0.0007 Tc -0.0007 Tw [(A a)9.7(n)4.7(d B lo)-8.3(ci o)12.7(r)0.7( b)-8.3(e)0.7(tw)8.7(een)]TJ 0.3735 -1 TD -0.0006 Tc 0.0006 Tw [(p)-9.6(o)6.4(l)6.4(y)-3.6(mo)11.4(r)-10.6(p)6.4(hic si)11.4(t)5.4(es in a)]TJ 1.4135 -1 TD [(D)8.4(N)37.4(A s)-8.6(e)-5.6(q)9.4(uence)]TJ -14.8325 -2.8166 TD 0.0008 Tc 0 Tw [(Reco)12.8(m)10.8(b)12.8(ina)9.8(n)19.8(t)]TJ 0 -1 TD -0.001 Tc [(ha)18(p)6(l)-1(o)10(t)-4(yp)-10(es)]TJ ET q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d /GS4 gs 455.912 374.412 m 269.464 374.412 l 269.464 365.469 l 455.912 365.469 l S Q /GS4 gs BT 8.1773 0 0 8.1773 272.8471 367.1944 Tm 0.8675 Tc [(ATA)49(G)36(C)-12.9(T)-1509.3(G)-1485.3(C)]TJ 9.1656 0 TD 2.3888 Tc [(TA)23.9(C)1508.4(T)-37(T)]TJ 9.0915 0 TD 2.34 Tc (AG)Tj ET q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d 282.075 374.263 m 282.075 365.419 l 294.029 374.263 m 294.029 365.419 l 306.885 374.263 m 306.885 365.419 l 330.959 374.263 m 330.959 365.419 l 318.84 374.263 m 318.84 365.419 l 344.633 374.263 m 344.633 365.419 l 357.489 374.263 m 357.489 365.419 l 381.563 374.263 m 381.563 365.419 l 369.444 374.263 m 369.444 365.419 l 395.319 374.263 m 395.319 365.419 l 419.393 374.263 m 419.393 365.419 l 407.274 374.263 m 407.274 365.419 l 443.958 374.263 m 443.958 365.419 l 431.839 374.263 m 431.839 365.419 l 455.749 374.263 m 455.749 365.419 l S Q 0 0 0 0.14999 k /GS5 gs 282.236 334.287 12.123 8.8742 re f 331.12 334.287 13.597 8.8742 re f 381.233 334.287 13.925 8.8742 re f 444.119 334.287 11.549 8.8742 re f q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d /GS4 gs 455.912 343.132 m 269.464 343.132 l 269.464 334.189 l 455.912 334.189 l S Q /GS4 gs BT 8.1773 0 0 8.1773 272.8471 335.9143 Tm /Cs8 cs 1 scn 0.8674 Tc [(AA)73.9(A)48.9(G)35.9(C)-13(C)-1461.4(G)-1485.4(G)]TJ 9.1656 0 TD 2.3888 Tc [(TA)23.9(C)1508.4(T)-37(T)]TJ 9.0915 0 TD 2.34 Tc (AA)Tj ET q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d 282.075 342.982 m 282.075 334.139 l 294.029 342.982 m 294.029 334.139 l 306.885 342.982 m 306.885 334.139 l 330.959 342.982 m 330.959 334.139 l 318.84 342.982 m 318.84 334.139 l 344.633 342.982 m 344.633 334.139 l 357.489 342.982 m 357.489 334.139 l 381.563 342.982 m 381.563 334.139 l 369.444 342.982 m 369.444 334.139 l 395.319 342.982 m 395.319 334.139 l 419.393 342.982 m 419.393 334.139 l 407.274 342.982 m 407.274 334.139 l 443.958 342.982 m 443.958 334.139 l 431.839 342.982 m 431.839 334.139 l 455.749 342.982 m 455.749 334.139 l S Q 0 0 0 0.14999 k /GS5 gs 282.236 260.591 12.123 8.8748 re f 331.12 260.591 13.597 8.8748 re f q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d /GS4 gs 455.912 269.437 m 269.464 269.437 l 269.464 260.494 l 455.912 260.494 l S Q /GS4 gs BT 8.1773 0 0 8.1773 272.8471 262.2196 Tm /Cs8 cs 1 scn 0.8674 Tc [(AA)73.9(A)48.9(G)35.9(C)-13(C)-1461.4(G)-1485.4(C)]TJ 9.1656 0 TD 2.3888 Tc [(TA)23.9(C)1508.4(T)-37(T)]TJ 9.0915 0 TD 2.34 Tc (AG)Tj ET q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d 282.075 269.287 m 282.075 260.444 l 294.029 269.287 m 294.029 260.444 l 306.885 269.287 m 306.885 260.444 l 330.959 269.287 m 330.959 260.444 l 318.84 269.287 m 318.84 260.444 l 344.633 269.287 m 344.633 260.444 l 357.489 269.287 m 357.489 260.444 l 381.563 269.287 m 381.563 260.444 l 369.444 269.287 m 369.444 260.444 l 395.319 269.287 m 395.319 260.444 l 419.393 269.287 m 419.393 260.444 l 407.274 269.287 m 407.274 260.444 l 443.958 269.287 m 443.958 260.444 l 431.839 269.287 m 431.839 260.444 l 455.749 269.287 m 455.749 260.444 l S Q 0 0 0 0.14999 k /GS5 gs 381.233 227.838 13.925 8.8748 re f 444.119 227.838 11.549 8.8748 re f q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d /GS4 gs 455.912 236.684 m 269.464 236.684 l 269.464 227.741 l 455.912 227.741 l S Q /GS4 gs BT 8.1773 0 0 8.1773 272.8471 229.4666 Tm /Cs8 cs 1 scn 0.8674 Tc [(AA)73.9(A)48.9(G)35.9(C)-13(C)-1461.4(G)-1485.4(G)]TJ 9.1656 0 TD 2.3888 Tc [(TA)23.9(C)1508.4(T)-37(T)]TJ 9.0915 0 TD 2.34 Tc (AA)Tj ET q 1 i 455.995 390.046 -341.995 -164.158 re 114 390.046 m W n /Cs8 CS 1 SCN 0 J 0 j 0.491 w 4 M []0 d 282.075 236.534 m 282.075 227.691 l 294.029 236.534 m 294.029 227.691 l 306.885 236.534 m 306.885 227.691 l 330.959 236.534 m 330.959 227.691 l 318.84 236.534 m 318.84 227.691 l 344.633 236.534 m 344.633 227.691 l 357.489 236.534 m 357.489 227.691 l 381.563 236.534 m 381.563 227.691 l 369.444 236.534 m 369.444 227.691 l 395.319 236.534 m 395.319 227.691 l 419.393 236.534 m 419.393 227.691 l 407.274 236.534 m 407.274 227.691 l 443.958 236.534 m 443.958 227.691 l 431.839 236.534 m 431.839 227.691 l 455.749 236.534 m 455.749 227.691 l S Q /Cs8 CS 1 SCN 0 J 0 j 0.983 w 4 M []0 d 1 i 365.053 322.839 m 365.053 292.87 l S 365.053 293.521 m 367.355 294.92 l 367.407 294.842 l 365.916 291.09 l 365.629 289.782 365.341 288.475 365.053 287.167 c 364.765 288.475 364.478 289.782 364.191 291.09 c 362.7 294.842 l 362.739 294.92 l 365.053 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This is,)]TJ T* 0.004 Tc 0.0175 Tw [(ho)15.5(w)7.4(e)-8.4(v)7.4(e)-0.6(r)62.6(,)-0.6( a p)-9.5(o)-9.4(o)11.6(r)-0.7( me)-6.5(asur)12.5(e o)11.6(f)-0.7( di)6.5(v)7.4(e)-0.6(r)5.4(s)-0.7(i)11.6(t)-3.7(y)72.2(.)-0.6( I)38.4(t)-0.7( is hig)-7.4(h)-5.6(l)6.3(y)-0.8( s)-6.6(a)8.3(m)18.4(p)6.3(le-size-dep)-9.5(enden)18.4(t, lik)8.4(e)]TJ T* -0.0053 Tc -0.0074 Tw [(t)-6.3(h)3.7(e co)11(un)18.7(ts o)11.9(f)-0.4( n)18.7(u)-0.5(m)9.7(b)-9.1(er)5.8(s o)11.9(f)-0.4( p)-9.2(o)6.8(l)6.6(y)-3.4(mo)11.9(r)-10.1(p)6.7(hic si)11.9(t)5.7(e)-0.3(s in a s)-8.3(e)-0.3(t o)11.9(f)-0.4( s)-8.3(e)-5.2(q)9.5(u)-0.5(ences \()]TJ /F1 1 Tf 25.7639 0 TD 0.0047 Tc -0.0173 Tw [(Bo)34(x)9.8( 1)9.7(.)9.8(3)]TJ /F6 1 Tf 3.0577 0 TD -0.0049 Tc -0.0078 Tw [(\), a)9(n)4.2(d)]TJ -28.8216 -1.1818 TD 0.0039 Tc 0.0218 Tw [(i)11.5(t)-0.8( a)-5.8(l)2.3(s)-8.7(o)-0.7( incr)12.4(e)-6.6(a)2.3(s)-8.7(e)-0.7(s wi)11.5(t)-6.7(h)-0.8( t)-6.7(h)3.3(e len)7.3(g)-0.7(t)-6.7(h)-0.8( o)11.5(f)-0.8( g)7.4(e)-0.7(no)11.5(me s)-8.7(e)-5.6(q)9.1(u)-0.9(enced)5.4(.)-0.7( One ca)8.2(n a)-5.8(l)2.3(s)-8.7(o)-0.7( me)-6.6(asur)12.4(e)]TJ T* -0.0061 Tc -0.0038 Tw [(ha)17.8(p)5.9(l)-1.2(o)10.2(t)-4.2(yp)-10(e di)6(v)6.9(e)-1.1(r)5(s)-1.2(i)11.1(t)-4.2(y)71.7(,)-1.1( j)8.8(u)1.9(st as wi)11.1(t)-7.1(h)-1.2( g)7(e)-1.1(ne di)6(v)6.9(e)-1.1(r)5(s)-1.2(i)11.1(t)-4.2(y \(s)-9.1(ee )]TJ /F1 1 Tf 19.9175 0 TD 0.0047 Tc -0.0146 Tw [(Bo)34(x)9.8( 1)9.7(.)9.8(2)]TJ /F6 1 Tf 3.0604 0 TD 0.0009 Tc -0.0108 Tw [(\))5.7(;)5.9( th)5.8(i)9(s)5.8( tak)14.9(e)5.9(s)5.8( th)9.9(e)5.9( sa)14.8(m)5.8(-)]TJ -22.9779 -1.1818 TD 0.0046 Tc 0.2551 Tw [(p)6.9(l)-0.1(e size in)19(t)6(o)0( acco)11.3(un)19(t, b)11.2(u)12(t i)12.2(t)-0.1( a)5(g)0(a)8.9(i)0(n dep)-8.9(ends o)12.2(n)-0.1( t)-6(h)4(e len)8(g)0(t)-6(h)-0.1( o)12.2(f)-0.1( t)-6(h)4(e r)13.1(e)0(gio)12.2(n)]TJ T* -0.0042 Tc -0.0008 Tw [(s)-8.3(e)-5.2(q)9.5(u)-0.5(enced)5.7(.)-0.3( I)38.7(t)-0.5( has t)-6.3(h)3.7(e f)-6.3(u)-0.5(r)-10.1(t)-6.3(her dis)-6.3(a)-0.5(d)6.7(v)-0.4(a)8.5(n)18.6(t)-6.3(a)4.6(g)7.8(e)-0.3( o)11.9(f)-0.4( igno)11.9(r)-6.2(i)-0.4(n)7.7(g)-0.3( all t)-6.3(h)3.7(e inf)8.6(o)11.9(r)-6.2(ma)18.5(tio)11.9(n)-0.4( f)-10.2(r)12.8(o)11.9(m)]TJ T* 0.0047 Tc 0.1171 Tw [(t)-5.9(h)4.1(e n)19.1(u)-0.1(m)10.1(b)-8.7(er)6.1(s a)9(n)4.2(d p)-8.8(o)0.1(si)12.3(tio)12.3(n)8.1(s o)12.3(f)0( s)-7.9(e)-4.8(q)9.9(u)-0.1(ence dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(nces b)-8.7(e)0.1(tw)8.1(een t)-5.9(h)4.1(e ha)19(p)7(l)0(o)11.4(t)-3(yp)-8.8(es)]TJ T* 0.0018 Tc -0.0068 Tw [(\(no)12(niden)18.7(tical ha)18.6(p)6.7(l)-0.4(o)11(t)-3.3(yp)-9.2(es a)8.6(r)12.9(e tr)12.9(e)-6.1(a)18.6(t)5.7(e)-5.2(d in t)-6.3(h)3.7(e s)-6.3(a)8.6(me ma)8.6(nner)62.9(, w)-7.1(h)3.7(et)-6.3(her t)-6.3(h)3.7(er)12.9(e is j)9.7(u)2.7(st)]TJ T* -0.0047 Tc -0.023 Tw [(o)12.5(n)4.4(e n)19.3(u)0.1(c)6.3(l)0.2(eo)11.6(tide dif)-9.6(f)9.2(e)0.3(r)13.4(e)0.3(nce)6.4(,)0.3( o)12.5(r)0.2( ma)9.2(n)23.4(y\).)]TJ /F1 1 Tf 3.7377 -2.3636 TD 0.05 Tc 0 Tw [(1.2.v)75.4(.)0.1(b)23.3(.)]TJ /F3 1 Tf 3.545 0 TD -0.0008 Tc 0.0008 Tw [(Th)6.3(e eff)9.2(e)5.4(ct o)10.5(f)-0.8( r)18.3(e)5.4(c)6.4(o)9.2(m)17.4(b)9.4(i)12.4(n)6.3(a)21.4(t)8.3(io)9.2(n o)9.2(n)-0.8( h)6.3(a)10.4(p)9.4(l)3.6(o)11.4(t)-0.7(y)-13.6(p)3.5(e va)15.3(r)-9.6(i)3.4(a)21.4(b)9.4(i)4.4(l)12.6(i)13.4(t)-0.7(y)]TJ /F6 1 Tf -7.2827 -1.1818 TD 0.004 Tc 0.119 Tw [(Ano)10.7(t)-6.6(her f)-6.6(u)-0.8(nda)8.3(m)3.5(en)18.4(t)-6.6(a)-5.7(l p)11.5(r)12.5(o)4.6(b)6.5(lem wi)11.6(t)-6.6(h)-0.7( me)-6.5(as)4.4(ur)-6.5(in)7.4(g D)8.4(N)37.4(A s)-8.6(e)-5.5(q)9.2(u)-0.8(ence di)6.5(v)7.4(e)-0.6(r)5.4(s)-0.7(i)11.6(t)-3.7(y b)15.5(y)]TJ T* 0.0043 Tc 0.0473 Tw [(co)11(un)18.7(tin)7.7(g)-0.3( ha)18.6(p)6.6(l)-0.4(o)11(t)-3.4(yp)-9.2(es \(a)18.6(t le)-6.2(as)4.7(t in n)18.7(u)-0.5(c)5.7(l)-0.4(e)-6.2(a)8.6(r g)7.8(e)-0.3(nes\) is t)-6.3(h)2.7(a)18.6(t)-0.4( g)7.8(e)-0.3(netic r)12.8(e)-5.2(co)11.9(m)9.7(b)11.9(ina)18.6(t)-5.3(io)11.9(n)]TJ T* 0.0045 Tc 0.0629 Tw [(a)8.8(m)4(o)12.1(n)7.9(g dif)-10(f)8.8(e)-0.1(r)13(e)-0.1(n)18.9(t)-0.2( ha)18.8(p)6.8(l)-0.2(o)11.2(t)-3.2(yp)-9(es a)8.8(f)-10(f)8.8(e)-5(c)-7(ts ha)18.8(p)6.8(l)-0.2(o)11.2(t)-3.2(yp)-9(e n)18.9(u)-0.3(m)9.9(b)-8.9(er)5.9(s. Reco)12.1(m)9.9(b)12.1(ina)18.8(t)-5.1(io)12.1(n do)-8.9(es)]TJ T* 0.0046 Tc 0.0437 Tw [(no)11.3(t a)8.9(f)-9.9(f)8.9(e)-4.9(c)-6.9(t)-0.1( di)7.1(v)8(e)0(r)6(s)-0.1(i)12.2(t)-3.1(y p)-8.9(e)0(r n)19(u)-0.2(c)6(l)-0.1(eo)11.3(tide si)12.2(t)6(e)6.1(, b)11.2(u)12(t mer)13.1(e)4.1(l)6.9(y)-0.2( distr)-5.9(i)4.1(b)11.2(u)12(t)6(e)0(s va)8.9(r)-5.9(i)-2.9(a)8.9(n)19(ts dif)-9.9(f)8.9(e)0(r-)]TJ T* 0.0044 Tc 0.1686 Tw [(en)18.8(t)-6.2(l)6.7(y a)8.7(m)3.9(o)12(n)7.8(g ha)18.7(p)6.7(l)-0.3(o)11.1(t)-3.3(yp)-9.1(es, in a p)11.9(r)12.9(o)-9(c)-0.3(ess in w)-7.1(h)-0.3(ic)5.8(h existin)7.8(g)-0.2( va)8.7(r)-6.1(i)-3.2(a)8.7(n)18.8(ts )30.7(m)-0.3(igra)18.7(t)5.8(e)57.9()]TJ T* 0.0016 Tc -0.035 Tw [(be)6.6(t)3.5(w)14.6(ee)6.6(n)6.5( th)10.6(e)6.6(m)6.5( \()]TJ /F1 1 Tf 6.0872 0 TD -0.0046 Tc -0.0278 Tw [(F)8.5(i)0.5(gur)8.6(e)0.6( 1.11)]TJ /F6 1 Tf 4.6117 0 TD -0.005 Tc -0.0284 Tw [(\). The s)-6(a)8.9(me n)19(u)-0.2(m)10(b)-8.8(er o)12.2(f)-0.1( p)-8.9(o)7.1(l)6.9(y)-3.1(mo)12.2(r)-9.8(p)7(hic n)19(u)-0.2(c)6(l)-0.1(eo)11.3(tide si)12.2(t)6(e)0(s)]TJ -10.6988 -1.1818 TD 0.0047 Tc 0.0366 Tw [(ca)9(n t)-5.9(h)19(us b)-8.7(e)0.1( p)12.2(r)13.2(es)-7.9(en)19.1(t in dif)-9.8(f)9(e)0.1(r)13.2(e)0.1(n)19.1(t)0( n)19.1(u)-0.1(m)10.1(b)-8.7(er)6.1(s o)12.3(f)0( ha)19(p)7(l)0(o)11.4(t)-3(yp)-8.8(es. 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This im)19.4(p)-8.5(o)12.6(r)-9.4(t)-5.6(a)9.3(n)19.4(t co)12.6(ncep)11.5(t)]TJ T* -0.0025 Tc 0.181 Tw [(a)11.8(p)4(p)-16(e)-13(ars)-7.2( ag)-7.1(ai)-7.1(n)-7.2( i)-7.1(n)-7.2( )]TJ /F1 1 Tf 7.3025 0 TD 0.0049 Tc 0.1653 Tw [(S)-12(e)-12.8(c)-5.8(t)5.2(i)-5.9(o)10(n 3.1.v)75.2(.)0(d)]TJ /F6 1 Tf 6.2652 0 TD 0.0052 Tc 0.1733 Tw [(, w)-6.3(h)4.6(en de)-5.3(a)-4.5(l)0.5(in)8.6(g wi)12.8(t)-5.4(h)0.5( kin s)-7.4(e)4.7(lec)-6.3(t)-4.4(io)12.8(n, a)9.5(n)4.7(d in)]TJ /F1 1 Tf -13.5676 -1.1818 TD 0.0086 Tc -0.0138 Tw [(S)-6.1(e)-7(ct)11(io)15.9(n)5.8( 5)5.7(.)5.8(1)5.7(.)5.8(i)9(.)5.8(b)]TJ /F6 1 Tf 5.9488 0 TD 0.0026 Tc -0.0076 Tw [(, w)-6.8(h)4.1(en w)8.1(e)0.1( des)-7.9(c)0(r)-5.8(i)4.2(b)-8.7(e)0.1( t)-5.9(h)4.1(e e)-7.8(v)8(o)7.2(l)12.1(u)12.1(t)-5(io)12.3(na)8.9(r)-28.8(y)-0.1( ef)-9.8(f)9(e)-4.8(c)-6.8(ts o)12.3(f)0( f)-9.8(ini)12.2(t)6(e)0.1( p)-8.9(o)11.3(p)11.2(u)-5(la)18.9(t)-5(i)0(o)12.3(n)]TJ -5.9488 -1.1818 TD -0.0048 Tc -0.0217 Tw [(size a)9.1(n)4.3(d co)12.4(n)8.2(s)0.1(ider t)-5.8(h)4.2(e a)9.1(n)4.3(cestr)-28.7(y)0( o)12.4(f)0.1( s)-7.8(e)-4.7(q)10(u)0(ences a)19.1(t)0.1( a lo)-8.6(c)-6.7(u)3.2(s. I)25.3(den)19.2(ti)12.4(ty b)16.3(y)0( des)-7.8(cen)19.2(t)0.1( is a)-4.9(l)3.2(s)-7.8(o)]TJ T* -0.0053 Tc -0.0073 Tw [(t)-6.3(h)3.7(e basis f)8.6(o)11.9(r coa)-5.4(l)-0.4(es)-8.3(cence t)-6.3(h)3.7(eo)11.9(r)-29.2(y)72.5(, w)-7.2(h)-0.4(ic)5.7(h is no)15.8(w widel)6.6(y)-0.5( us)-8.3(ed f)8.6(o)11.9(r mo)-9.1(delin)7.7(g)-0.3( mo)6.8(lec-)]TJ T* -0.0059 Tc -0.0218 Tw [(u)-6(l)-4(a)8(r)-1( va)8(r)-6.8(i)-3.9(a)18(t)-5.9(io)11.3(n, as dis)-8.9(c)-7.8(uss)-8.9(e)-5.8(d in )]TJ /F1 1 Tf 11.706 0 TD -0.0052 Tc [(C)-12.9(h)0(a)15.1(p)8(t)12.1(e)5.2(rs 5)]TJ /F6 1 Tf 4.6174 0 TD -0.0115 Tc 0 Tw [(and)-6.5( )]TJ /F1 1 Tf 1.6854 0 TD 0 Tc (6)Tj /F6 1 Tf 0.495 0 TD (.)Tj -17.4129 -1.1818 TD 0.0049 Tc 0.0978 Tw [(T)73.1(w)8.3(o a)-4.8(l)-4.7(leles a)9.2(r)13.4(e s)-5.7(a)9.2(id t)6.3(o)0.3( b)-8.5(e)0.3( iden)19.3(tica)-4.8(l b)16.4(y)0.1( des)-7.7(cen)19.3(t)0.2( o)12.5(r)0.2( )]TJ /F3 1 Tf 20.481 0 TD 0.0046 Tc 0 Tw [(i.b)39(.d.)]TJ /F6 1 Tf 2.2905 0 TD 0.0051 Tc 0.0976 Tw [(if t)-5.5(h)4.5(e)-7.3(y)0.3( trace t)-5.5(h)4.5(eir)]TJ -23.8624 -1.1818 TD 0.0053 Tc 0.1634 Tw [(a)9.6(n)4.8(ces)5.7(t)-4.3(r)-28.2(y)0.5( bac)6.7(k)0.6( \(o)12.9(r )]TJ /F3 1 Tf 7.6883 0 TD -0.0025 Tc 0 Tw [(coales)-10.1(ce)]TJ /F6 1 Tf 3.1085 0 TD 0.005 Tc 0.1637 Tw [(\) t)6.4(o)0.4( t)-5.6(h)4.4(e s)-5.6(a)9.3(me a)9.3(n)4.5(ces)5.4(t)-4.6(ral allele \()]TJ /F1 1 Tf 12.9196 0 TD 0.0055 Tc 0 Tw [(F)8.6(i)0.6(gur)8.7(e)-377.1(1.12)]TJ /F6 1 Tf 4.9049 0 TD 0.0031 Tc 0.1656 Tw [(\); t)-7.5(h)-1.6(is)]TJ -28.6212 -1.1818 TD -0.0014 Tc -0.0036 Tw [(inc)5.4(l)11.4(udes t)-6.7(h)3.3(e cas)-8.6(e)-0.7( w)-7.5(h)3.3(en o)11.6(n)3.4(e allele is des)-8.6(cended f)-10.5(r)12.5(o)11.6(m)-0.7( t)-6.7(h)3.3(e o)10.6(t)-6.7(her)62.5(.)-0.7( W)96.3(e)-0.7( a)8.2(r)12.5(e no)10.6(t co)11.6(n-)]TJ T* -0.0041 Tc -0.0009 Tw [(cer)-6(ned her)13.1(e)-0.1( wi)12.1(t)-6(h)-0.2( t)-6(h)4(e st)-6(a)18.8(t)5.9(es o)12.2(f)-0.2( t)-6(h)4(es)-8(e alleles wi)12.1(t)-6(h)-0.2( r)13.1(e)-0.1(sp)-9(ec)-6.9(t t)5.9(o)0( t)-6(h)4(eir D)8.9(N)37.9(A s)-8(e)-4.9(q)9.8(u)-0.3(ences)]TJ T* 0.0052 Tc -0.0001 Tw [(\(if m)19.6(u)12.6(t)-5.4(a)19.5(tio)12.8(n)8.6(s o)-8.2(c)0.5(c)-6.3(u)0.4(r)-5.3(r)13.7(ed d)12.8(u)0.4(r)-5.3(i)0.6(n)8.6(g)0.6( t)-5.4(h)4.6(e time in)19.6(t)6.6(e)0.6(r)-28.3(v)0.5(a)-4.5(l)0.5( b)-8.2(e)0.6(tw)8.6(een t)-5.4(h)4.6(e p)12.7(r)13.7(es)-7.4(en)19.6(t time a)9.5(n)4.7(d)]TJ T* -0.0049 Tc -0.0081 Tw [(t)-5.9(h)4.1(e time w)-6.8(h)4.1(en t)-5.9(h)4.1(e tw)8.1(o a)-5(l)-4.9(leles coa)-5(l)0(es)-7.9(ce in)19.1(t)6.1(o)0.1( t)-5.9(h)4.1(eir a)9(n)4.2(cestra)-5(l a)-5(l)-4.9(lele)6.2(, t)-5.9(h)4.1(e)-7.7(y)-0.1( mig)-6.7(h)19(t dif-)]TJ T* 0.0048 Tc 0.0215 Tw [(f)9.1(e)0.2(r in s)-7.8(e)-4.7(q)10(u)0(ence)6.3(, b)11.4(u)12.2(t, acco)12.4(r)13.3(din)8.2(g t)6.2(o)0.2( t)-5.8(h)4.2(e def)-9.7(ini)12.4(t)-4.8(io)12.4(n j)10.1(u)3.2(st gi)7.3(v)8.2(e)0.2(n, t)-5.8(h)4.2(e a)-4.9(l)-4.8(leles a)9.1(r)13.3(e still)]TJ T* -0.0042 Tc -0.0008 Tw [(i.)-7.8(b)21.3(.)-7.8(d.)-7.8(\))-7.9(.)-7.8( I)8.3(f)-7.9( we)-7.8( t)-13.8(a)-12.8(ke)-7.8( t)-10.8(w)0.3(o)-7.7( i)-7.8(n)-3.7(d)-7.8(i)-0.7(v)-10.8(i)-7.8(d)4.4(u)-10.9(a)-12.8(l)-4.7(s)-7.9( )]TJ /F3 1 Tf 13.2902 0 TD 0 Tc 0 Tw (C)Tj /F6 1 Tf 0.8605 0 TD -0.0029 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.7338 0 TD 0 Tc (D)Tj /F6 1 Tf 0.9335 0 TD 0.0043 Tc -0.0093 Tw [(f)-9.1(r)13.9(o)13(m)0.7( a p)-8.2(e)-4.2(digr)13.9(e)-4.2(e \()]TJ /F1 1 Tf 6.9264 0 TD -0.0095 Tw [(F)8.5(i)0.5(gur)8.6(e)0.6( 1.12A)]TJ /F6 1 Tf 5.4379 0 TD 0.0037 Tc -0.0087 Tw [(\), w)8.2(e)]TJ -29.1823 -1.1818 TD 0.0072 Tc 0.0246 Tw [(ca)11.5(n calcula)21.5(t)8.6(e th)6.6(e p)14.7(r)15.7(o)7.8(b)-2.3(a)10.5(b)14.8(ili)14.8(t)-0.5(y)75.4(,)2.6( )]TJ /F3 1 Tf 11.8365 0 TD 0 Tc 0 Tw (f)Tj 7.7 0 0 6.6 265.2349 372.3699 Tm 0.0045 Tc (CD)Tj /F6 1 Tf 11 0 0 11 275.6458 376 Tm 0.005 Tc 0.0268 Tw [(, t)-5.6(h)3.4(a)19.3(t)0.3( a)9.3(n)0.3( allele a)19.3(t)0.3( a)9.3(n)0.3( a)19.3(u)12.4(t)6.4(o)0.4(s)-7.6(o)12.6(mal lo)-8.4(c)-6.5(u)3.4(s, c)6.4(h)4.4(os)-7.6(en)]TJ -13.0587 -1.1818 TD -0.0076 Tc 0.0272 Tw [(r)-12.3(a)-3.3(n)-8.1(d)-12.2(om)-17.1(l)-5.3(y)-12.4( f)-22.1(r)0.9(om)-12.3( i)-12.2(n)-8.1(d)-12.2(i)-5.1(v)-15.2(i)-12.2(du)-15.3(a)-17.3(l)-12.3( )]TJ /F3 1 Tf 10.8017 0 TD 0 Tc 0 Tw (C)Tj /F6 1 Tf 0.6395 0 TD 0.0196 Tc [(,)15( i)18.1(s)14.9( i)21.1(.)15(b)44(.)15(d)21.1(.)15( w)12.1(i)27.2(t)9(h)14.9( a)23.9(n)14.9( a)9.9(l)10(l)14.9(e)19.1(l)14.9(e)15( c)21(h)19(o)15(s)7(e)15(n)14.9( r)14.9(a)23.9(n)19.1(d)15(o)27.2(m)10.1(l)21.9(y)14.8( f)5.1(r)28.1(o)27.2(m)14.9( )]TJ /F3 1 Tf 18.7093 0 TD 0 Tc (D)Tj /F6 1 Tf 0.7125 0 TD (.)Tj -30.8632 -1.1818 TD 0.005 Tc 0.064 Tw [(This is ca)-4.7(lled t)-5.6(h)4.4(e indi)7.5(vid)12.6(u)-2.7(a)-4.7(l)26.4()95.5(s)0.3( )]TJ /F3 1 Tf 12.1746 0 TD 0.0043 Tc 0.0656 Tw [(c)6.8(o)3.7(eff)-8.3(i)3.7(cien)21.8(t o)10.8(f)-0.5( k)16.6(i)12.8(ns)12.8(h)16.6(i)9.6(p)]TJ /F6 1 Tf 8.4563 0 TD 0.0045 Tc 0.0645 Tw [(\(s)-8.1(o)12.1(m)4(etimes kno)16(w)-3(n as t)-6.1(h)3.9(e)]TJ ET 1 g 87 696 387 12 re f BT 10 0 0 10 87 700.7319 Tm 0.017 g 0 Tc 0 Tw (36)Tj /F8 1 Tf 11.0033 0 TD 0.1514 Tc -0.0003 Tw ( \012)Tj /F6 1 Tf 7.6614 0 TD -0.0005 Tc 0.0003 Tw [(| )-253.2(V)98.7(a)8.6(r)-6.2(i)-3.3(a)7.6(b)11.9(ili)11.9(t)-3.4(y a)8.6(n)3.8(d I)38.7(ts M)25.7(e)-6.2(asur)12.8(emen)18.7(t)]TJ ET /Document /MC12 BDC Q /GS3 gs BT /F6 1 Tf 8.5 0 0 8.5 207.4842 298.7844 Tm /Cs8 cs 1 scn 0 Tc 0 Tw (A)Tj 7.973 0.0001 TD (B)Tj -7.96 -2.8629 TD 7.2215 Tc (CD)Tj 4.1021 -4.2915 TD 0 Tc (E)Tj ET /Cs8 CS 1 SCN 0 J 0 j 0.5 w 4 M []0 d /GS4 gs 1 i 227.42 297.42 m 227.42 297.42 -8.6669 8.667 re S 0 0 0 1 k /GS5 gs 227.42 297.42 m 218.753 297.42 l 218.753 306.087 l 227.42 297.42 l f* /GS4 gs 227.42 273.087 m 227.42 273.087 -8.6669 8.6661 re S /GS5 gs 227.42 273.087 m 218.753 273.087 l 218.753 281.753 l 227.42 273.087 l f* 266.253 272.025 m 263.399 272.025 261.086 274.338 261.086 277.191 c 261.086 280.045 263.399 282.357 266.253 282.357 c 266.232 279.982 266.232 275.816 266.253 272.025 c f* /GS4 gs 271.419 277.191 m 271.419 274.338 269.106 272.025 266.253 272.025 c 263.399 272.025 261.086 274.338 261.086 277.191 c 261.086 280.045 263.399 282.357 266.253 282.357 c 269.106 282.357 271.419 280.045 271.419 277.191 c h 271.419 302.023 m 271.419 299.17 269.106 296.856 266.253 296.856 c 263.399 296.856 261.086 299.17 261.086 302.023 c 261.086 304.877 263.399 307.189 266.253 307.189 c 269.106 307.189 271.419 304.877 271.419 302.023 c s /GS5 gs 250.042 250.938 m 250.042 248.085 247.729 245.772 244.876 245.772 c 242.022 245.772 239.709 248.085 239.709 250.938 c 239.709 253.792 242.022 256.105 244.876 256.105 c 247.729 256.105 250.042 253.792 250.042 250.938 c f* 0 0 0 0.75 K 0.444 w 326.848 267.191 m 326.848 285.693 l 318.258 285.694 m 337.758 285.694 l 315.681 287.859 m 315.681 293.86 l 378.012 293.86 l 378.012 287.692 l 339.181 293.86 m 339.181 288.693 l 350.862 294.027 m 350.862 309.862 l 360.441 293.902 m 360.441 271.275 l 362.721 269.4 m 389.844 269.4 l 375.846 269.525 m 375.846 250.523 l 379.596 285.721 m 404.594 285.721 l 391.294 285.902 m 391.294 270.775 l 339.348 249.203 m 376.221 249.203 l 355.471 249.148 m 355.471 233.271 l 319.223 232.957 m 354.471 232.957 l 336.241 233.021 m 336.241 217.146 l S 0 0 0 0 k 313.091 283.063 5.261 5.2607 re f /Cs8 CS 1 SCN 0.5 w /GS4 gs 318.352 283.063 m 318.352 283.063 -5.261 5.2607 re S /GS5 gs 375.382 283.091 5.261 5.2608 re f /GS4 gs 380.643 283.091 m 380.643 283.091 -5.261 5.2608 re S /GS5 gs 357.81 266.745 5.261 5.2608 re f /GS4 gs 363.071 266.745 m 363.071 266.745 -5.261 5.2608 re S 0 0 0 0.75 K 0.444 w /GS5 gs 316.717 234.02 m 316.717 267.191 l 337.55 267.191 l 337.55 251.688 l S 334.884 246.573 5.261 5.2607 re f /Cs8 CS 1 SCN 0.5 w /GS4 gs 340.145 246.573 m 340.145 246.573 -5.261 5.2607 re S /GS5 gs 314.122 230.327 5.262 5.2607 re f /GS4 gs 319.384 230.327 m 319.384 230.327 -5.262 5.2607 re S 0 0 0 1 k /GS5 gs 333.61 213.02 5.261 5.261 re f /GS4 gs 338.871 213.02 m 338.871 213.02 -5.261 5.261 re S 0 0 0 0.75 K 0.444 w /GS5 gs 339.833 309.723 m 362.997 309.723 l S 0 0 0 0 k 334.666 307.093 5.261 5.2607 re f /Cs8 CS 1 SCN 0.5 w /GS4 gs 339.927 307.093 m 339.927 307.093 -5.261 5.2607 re S /GS5 gs 367.058 309.723 m 367.058 307.993 365.654 306.588 363.922 306.588 c 362.19 306.588 360.785 307.993 360.785 309.723 c 360.785 311.455 362.19 312.859 363.922 312.859 c 365.654 312.859 367.058 311.455 367.058 309.723 c f* /GS4 gs 367.058 309.723 m 367.058 307.993 365.654 306.588 363.922 306.588 c 362.19 306.588 360.785 307.993 360.785 309.723 c 360.785 311.455 362.19 312.859 363.922 312.859 c 365.654 312.859 367.058 311.455 367.058 309.723 c s /GS5 gs 342.317 285.694 m 342.317 283.964 340.913 282.557 339.181 282.557 c 337.449 282.557 336.045 283.964 336.045 285.694 c 336.045 287.425 337.449 288.829 339.181 288.829 c 340.913 288.829 342.317 287.425 342.317 285.694 c f* /GS4 gs 342.317 285.694 m 342.317 283.964 340.913 282.557 339.181 282.557 c 337.449 282.557 336.045 283.964 336.045 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T)92.9(a)-4(kin)9(g)1.1( in)20(t)7(o)1.1( acco)12.3(un)20(t all f)10(o)12.3(ur eq)10.9(uall)8(y p)13.1(r)14.2(o)6.2(b)-3.8(a)8.9(b)8.1(le co)13.3(m)11(b)13.2(ina)19.9(t)-4(io)13.3(n)9(s)0.9( o)13.3(f)0.9( o)13.3(r)-4.9(igin)9(s o)13.3(f)]TJ T* -0.0044 Tc -0.0233 Tw [(alleles, w)8.6(e)0.6( g)8.7(e)0.6(t:)]TJ 29.2305 -2.7729 TD -0.0048 Tc 0 Tw (\(1.2\))Tj -29.2305 -2.3182 TD 0.0013 Tc -0.0063 Tw [(A)40.9(p)11.1(p)7(l)7(y)-3.1(in)8(g t)-5.9(h)-0.1(is r)-9.8(u)-5(le co)12.3(n)8(s)-0.1(ist)6(e)0(n)19(t)-5.9(l)7(y)-0.1( t)6(o)0.1( a sp)-8.9(ecif)-9.8(ied p)-8.9(e)-4.8(digr)13.2(e)-4.8(e)6.1(,)0.1( w)8.1(e)0( ca)8.9(n o)5.2(b)11.3(t)-5.9(a)8.9(in a g)8.1(e)0(neral)]TJ 0 -1.1818 TD -0.0156 Tc 0.0077 Tw [(for)-16.5(m)8.4(u)-15.7(l)-13.7(a)-10.8( for)-10.7( t)-16.6(h)-6.6(e)-10.6( )]TJ /F3 1 Tf 6.2074 0 TD 0 Tc 0 Tw (f)Tj /F6 1 Tf 0.4854 0 TD -0.0049 Tc -0.003 Tw [(va)-5(l)12.2(u)-0.1(e o)12.3(f)0( a pa)9(ir o)12.3(f)0( indi)7.2(vid)12.3(u)-3(a)-5(l)3.1(s in t)6.1(e)0.1(r)-5.8(m)8.1(s o)12.3(f)0( t)-5.9(h)4.1(e in)10(b)12.3(r)13.2(eedin)8.1(g co)-8.7(ef)-9.8(f)-9.8(i)0.1(-)]TJ -6.6927 -1.1818 TD 0.0043 Tc 0.0264 Tw [(cien)18.7(ts o)11.9(f)-0.4( a)-5.4(l)-5.3(l t)-6.3(h)3.7(eir co)11.9(mmo)11.9(n)-0.4( a)8.6(n)3.8(cest)5.7(o)11.9(r)5.7(s in t)-6.3(h)3.7(e p)-9.2(e)-5.2(digr)12.8(e)-5.2(e \()]TJ /F1 1 Tf 21.6806 0 TD 0.0147 Tc 0 Tw [(Bo)34(x)-236.2(1)9.7(.)9.8(4)]TJ /F6 1 Tf 3.1593 0 TD 0.0047 Tc (\). )Tj /F1 1 Tf 0.8411 0 TD 0.0054 Tc 0.0235 Tw [(F)8.5(i)0.5(gur)8.6(e)0.6( 1.12B)]TJ /F6 1 Tf -25.6809 -1.1818 TD -0.005 Tc -0.0227 Tw [(sho)16.1(ws a)8.9(n)-0.1( exa)8.9(m)19(p)7(l)-0.1(e o)12.2(f)-0.1( a p)-8.9(e)-4.9(digr)13.1(e)-4.9(e f)8.9(o)12.2(r a na)18.9(t)9.9(u)-0.2(ra)-5.1(l p)-8.9(o)11.3(p)11.1(u)-5.1(la)18.9(tio)12.2(n)-0.1(.)]TJ ET 1 g 209.071 495.498 151.858 27 re f Q 0 G 0 J 0 j 0.5 w 10 M []0 d /GS2 gs 1 i 240.602 506.467 m 247.165 506.467 l S BT /F3 1 Tf 11 0 0 11 212.6648 503.4979 Tm 0 g 3.4449 Tc 0 Tw [(ff)1014.2(f)1062.5(f)1107.9(f)]TJ 6.375 0 0 6.375 215.2898 499.9667 Tm 0.0035 Tc [(C)-28.2(D)-5112(AA)-3327.6(AB)-3309.7(BA)-3249.2(BB)]TJ /F17 1 Tf 11 0 0 11 229.7898 503.4979 Tm 3.2635 Tc [(=+)1159.1(+)1204.5(+)]TJ 11 0 0 17.248 247.9773 502.4667 Tm 0 Tc (\()Tj 11 0 0 17.655 354.6648 502.3417 Tm (\))Tj 6.375 0 0 6.375 323.5085 499.1542 Tm ()Tj /F6 1 Tf 11 0 0 11 241.1648 510.5604 Tm (1)Tj 0.0085 -1.3494 TD (4)Tj /F7 1 Tf 6.375 0 0 6.375 265.6335 499.9667 Tm 4.4099 Tc [()-4318.6()]TJ ET q 0 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n 1 g 114 696 387 12 re f BT /F6 1 Tf 10 0 0 10 142.8802 700.7319 Tm 0.017 g 0.1439 Tc 0.2531 Tw (1.3 | )Tj /F8 1 Tf 3.2746 0 TD 0.151 Tc 0.0001 Tw [( )64( \012 \015\012\012)26.8(\012 )88.9(\015\015\015)-15.1()]TJ /F6 1 Tf 31.5775 0 TD 0 Tc 0 Tw (37)Tj ET 0.902 g 114 142 342 247.941 re f BT /F1 1 Tf 11 0 0 11 127.4747 369.9462 Tm 0.017 g 0.0597 Tc -0.0099 Tw [(Bo)34(x)9.8( 1)9.7(.)9.8(4)]TJ /F2 1 Tf 3.8198 0 TD 0.1448 Tc -0.0001 Tw [(C)-7.9(O)9.9(EFFI)11.2(CIENT)-8.7(S)0( O)9.9(F)0( KINS)12.2(HIP IN A P)5.2(E)0.1(D)10.2(I)11.2(GREE)]TJ /F6 1 Tf -3.9539 -2.3636 TD -0.0042 Tc -0.0252 Tw [(I)16.9(n)0.7( a)9.7(n)0.7( a)9.7(r)0.7(b)13(i)13(t)-4.2(ra)9.7(r)-28.1(y)0.6( p)-8.1(e)-4.1(digr)13.9(e)-4.1(e)6.9(,)0.8( w)8.8(e)0.8( ca)9.7(n designa)19.7(t)6.8(e)0.8( t)-5.2(h)4.8(e tw)8.8(o pa)9.7(r)13.9(e)0.8(n)19.8(ts o)13(f)0.7( a)9.7(n)0.7( indi)7.9(vid)13(u)-2.3(a)-4.3(l)]TJ /F3 1 Tf 0 -1.1818 TD 0 Tc 0 Tw (E)Tj /F6 1 Tf 0.7555 0 TD -0.0065 Tc (as )Tj /F3 1 Tf 0.9946 0 TD 0 Tc (C)Tj /F6 1 Tf 0.8315 0 TD -0.0115 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.6876 0 TD 0 Tc (D)Tj /F6 1 Tf 0.9045 0 TD -0.0045 Tc [(\(e)6.6(.g., )]TJ /F1 1 Tf 2.0914 0 TD -0.0046 Tc -0.0202 Tw [(F)8.5(i)0.5(gur)8.6(e)0.6( 1.12A)]TJ /F6 1 Tf 5.32 0 TD -0.0049 Tc 0 Tw (\). )Tj /F3 1 Tf 0.7656 0 TD 0 Tc (C)Tj /F6 1 Tf 0.8315 0 TD -0.0115 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.6876 0 TD 0 Tc (D)Tj /F6 1 Tf 0.9045 0 TD -0.0048 Tc -0.0207 Tw [(ma)18.1(y trace t)-5.8(h)4.2(eir des)-7.8(cen)19.2(t)0.1( bac)6.3(k)0.1( t)6.2(o)]TJ -16.7741 -1.1818 TD -0.0105 Tw [(a n)19.1(u)-0.1(m)10.1(b)-8.7(er )]TJ /F3 1 Tf 4.0085 0 TD 0 Tc 0 Tw (m)Tj /F6 1 Tf 0.9937 0 TD -0.0057 Tc -0.0097 Tw [(o)11.5(f)-0.8( co)11.5(mmo)11.5(n)-0.8( a)8.2(n)3.4(ces)4.3(t)5.3(o)11.5(r)5.4(s. D)-6.6(e)-0.7(no)10.6(t)5.3(e)-0.7( t)-6.7(h)3.3(es)-8.7(e co)11.5(mmo)11.5(n)-0.8( a)8.2(n)3.4(ces)4.3(t)5.3(o)11.5(r)5.4(s b)15.4(y)-0.9( )]TJ /F3 1 Tf 23.0567 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 441.8985 314.3162 Tm (i)Tj /F6 1 Tf 11 0 0 11 126 304.9462 Tm (\()Tj /F3 1 Tf 0.3412 0 TD (i)Tj /F6 1 Tf 0.4862 0 TD -0.0055 Tc -0.0035 Tw (= 1, 2, )Tj /F7 1 Tf 2.6254 0 TD 0 Tc 0 Tw ()Tj /F6 1 Tf 0.995 0 TD -0.005 Tc (, )Tj /F3 1 Tf 0.441 0 TD 0 Tc (m)Tj /F6 1 Tf 0.7821 0 TD -0.0064 Tc -0.0026 Tw [(; i)10.8(t)-1.5( is, o)10.8(f)-1.5( co)9.9(ur)4.7(s)-9.4(e)4.7(, p)-10.3(o)-1.4(ssib)5.7(le)4.7(, f)7.5(o)10.8(r o)10.8(n)2.7(e o)10.8(r)-1.5( mo)10.8(r)11.7(e)-1.4( o)10.8(f)-1.5( t)-7.4(h)2.6(es)-9.4(e a)7.5(n)2.7(cest)4.6(o)10.8(r)4.7(s)]TJ -5.6709 -1.1818 TD 0.0038 Tc 0.0236 Tw [(t)5.2(o)-0.8( b)-9.6(e)-0.8( a)8.1(n)-0.9( a)8.1(n)3.3(cest)5.2(o)11.4(r)-0.9( o)11.4(f)-0.9( o)11.4(n)3.3(e o)11.4(r)-0.9( mo)11.4(r)12.3(e)-0.8( o)11.4(f)-0.9( t)-6.8(h)3.2(e o)10.5(t)-6.8(her)5.2(s)-0.9(\). B)7.2(y)-1( exa)8.1(m)-0.9(inin)7.2(g t)-6.8(h)3.2(e p)-9.7(e)-5.7(di-)]TJ T* -0.0033 Tc -0.0244 Tw [(gr)14.8(ee)7.8(, w)9.7(e)1.7( ca)10.6(n iden)20.7(tif)-15.2(y)1.5( e)-4.2(a)1.5(c)7.7(h)1.6( pa)20.6(t)-4.3(h)1.6( t)-4.3(h)4.7(a)20.6(t)1.6( co)13.9(nnec)-5.2(ts )]TJ /F3 1 Tf 17.6421 0 TD 0 Tc 0 Tw (C)Tj /F6 1 Tf 0.8293 0 TD -0.0115 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.6854 0 TD 0 Tc (D)Tj /F6 1 Tf 0.9023 0 TD -0.011 Tc [(to)-6( )]TJ /F3 1 Tf 0.9983 0 TD 0 Tc (A)Tj 7.7 0 0 6.6 375.8821 275.3162 Tm (i)Tj /F6 1 Tf 11 0 0 11 377.947 278.9462 Tm (.)Tj -21.8134 -1.1818 TD -0.0043 Tc -0.0007 Tw [(L)-8.4(o)-8.3(o)7.5(k)-3.5(in)8.4(g do)16.6(wn o)12.7(n)4.5(e o)12.7(f)0.3( t)-5.6(h)4.4(es)-7.5(e pa)19.3(t)-5.6(h)8.3(s, t)-5.6(h)4.4(er)13.6(e is a p)12.5(r)13.6(o)5.6(b)-4.5(a)8.3(b)12.6(ili)12.6(t)-2.6(y o)12.7(f)0.3( o)12.7(n)4.5(e-half \(f)9.4(o)12.7(r)]TJ -1.0909 -1.1818 TD 0.0049 Tc 0.0499 Tw [(a)9.2(n)0.2( a)19.2(u)12.3(t)6.3(o)0.3(s)-7.7(o)12.5(mal lo)-8.5(c)-6.6(u)3.3(s\) t)-5.7(h)3.3(a)19.2(t)0.2( t)-5.7(h)4.3(e s)-5.7(a)9.2(me allele o)12.5(f)0.2( )]TJ /F3 1 Tf 17.6988 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 328.0416 249.3162 Tm (i)Tj /F6 1 Tf 11 0 0 11 333.2802 252.9462 Tm 0.0056 Tc 0.0492 Tw [(is tra)9.9(n)9(smi)13.2(t)10.9(t)7(ed t)7(o)1( t)-5(h)5(e tw)9(o)]TJ -18.8437 -1.1818 TD -0.0049 Tc -0.0315 Tw [(p)12.2(r)13.2(og)8.2(en)23.2(y o)12.3(f)0( )]TJ /F3 1 Tf 4.3778 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 181.4059 236.3162 Tm (i)Tj /F6 1 Tf 11 0 0 11 185.5676 239.9462 Tm -0.005 Tc -0.0314 Tw [(t)-6(h)3(a)18.9(t)-0.1( co)12.2(n)8(s)5(ti)12.2(t)9.9(u)12(t)6(e)0( t)-6(h)4(e next st)6(ep in t)-6(h)4(e pa)18.9(t)-6(h)-0.1(. Ther)13.1(e is a)-5.1(l)3(s)-8(o)0( a p)12.1(r)13.1(o)5.2(b)0(-)]TJ -5.4152 -1.1818 TD 0.0052 Tc 0.0984 Tw [(a)8.5(b)12.8(ili)12.8(t)-2.5(y o)12.8(f)0.5( o)12.8(n)4.7(e-half t)-5.4(h)3.6(a)19.5(t)0.5( a ma)19.5(t)6.6(e)0.6(r)-5.3(n)3.7(al allele is tra)9.5(n)8.6(smi)12.8(t)10.5(t)6.6(ed t)6.6(o)0.6( o)12.8(n)4.7(e o)12.8(f)0.5( t)-5.4(h)4.6(es)-7.4(e)]TJ T* -0.0044 Tc -0.0006 Tw [(p)12.6(r)13.7(og)8.6(en)23.6(y a)9.4(n)4.6(d a pa)19.4(t)6.5(e)0.5(r)-5.4(n)3.6(al allele t)6.5(o)0.6( t)-5.5(h)4.5(e o)11.8(t)-5.5(her)63.7(.)0.5( I)16.6(n)0.4( t)-5.5(h)0.4(is cas)-7.4(e)6.6(, t)-5.5(h)4.5(e p)12.6(r)13.7(o)5.7(b)-4.4(a)8.4(b)12.7(ili)12.7(t)-2.5(y t)-5.5(h)3.6(a)19.4(t)]TJ T* 0.0049 Tc 0.0274 Tw [(t)-5.7(h)4.3(e)-7.5(y)0.1( a)9.2(r)13.4(e i)6.4(.)0.3(b)29.3(.)0.3(d)6.4(.)0.3( is t)-5.7(h)4.3(e in)10.2(b)12.5(r)13.4(eedin)8.3(g co)-8.5(ef)-9.6(f)-9.6(i)0.3(cien)19.3(t o)12.5(f)0.2( )]TJ /F3 1 Tf 18.3649 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 335.3685 197.3162 Tm (i)Tj /F6 1 Tf 11 0 0 11 337.5069 200.9462 Tm 0.0047 Tc 0.0276 Tw [(, deno)11.4(t)6.1(ed b)16.2(y)-0.1( )]TJ /F3 1 Tf 5.2546 0 TD 0 Tc 0 Tw (f)Tj 7.7 0 0 6.6 397.2917 197.3162 Tm (A)Tj 6.3 0 0 5.4 402.4398 195.9762 Tm (i)Tj /F6 1 Tf 11 0 0 11 404.1894 200.9462 Tm 0.0036 Tc 0.0287 Tw (. The net)Tj -25.2899 -1.1818 TD -0.005 Tc -0.015 Tw [(p)12.1(r)13.1(o)5.2(b)-4.9(a)7.9(b)12.2(ili)12.2(t)-3.1(y t)-6(h)3(a)18.9(t)-0.1( t)-6(h)4(e tw)8(o g)8.1(e)0(nes a)8.9(r)13.1(e i)6.1(.)0(b)29(.)0(d)6.1(.)0( i)12.8(s)9.5( )9.6(th)28.5(u)12.6(s)9.5( )9.6(\()9.5(1)9.4( )9.6(+)9.6( )]TJ /F3 1 Tf 19.7639 0 TD 0 Tc 0 Tw (f)Tj 7.7 0 0 6.6 346.2259 184.3162 Tm (A)Tj 6.3 0 0 5.4 351.2271 182.9761 Tm (i)Tj /F6 1 Tf 11 0 0 11 352.8567 187.9462 Tm -0.014 Tc -0.0156 Tw [(\)/2. This is eq)10.4(ui)7.7(val)-9.1(e)-9(n)10(t)]TJ -20.6233 -1.1818 TD 0.0051 Tc 0.0222 Tw [(t)6.5(o)0.5( t)-5.5(h)4.5(e in)10.4(b)12.7(r)13.6(eedin)8.5(g co)-8.3(ef)-9.4(f)-9.4(i)0.5(cien)19.5(t o)12.7(f)0.4( a)9.4(n)0.4( indi)7.6(vid)12.7(u)-2.6(a)-4.6(l)0.4( p)12.6(r)13.6(o)-8.3(d)12.7(uced b)16.6(y)0.3( s)-7.5(e)4.6(lf-f)9.4(e)0.5(r)-9.3(t)-4.5(iliza-)]TJ T* -0.0172 Tc -0.0105 Tw [(t)-17.2(i)-12.2(on)-12.3( of)-12.3( )]TJ /F3 1 Tf 2.7854 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 163.8891 158.3162 Tm (i)Tj /F6 1 Tf 11 0 0 11 165.954 161.9462 Tm (.)Tj ET 1 g 41 791 262.396 13.015 re f BT /F10 1 Tf 8 0 0 8 45 795 Tm 0 g (ch01_5401.qxp:Charlesworth 11/6/09 2:56 PM Page 37)Tj ET 1 G 42 780 m 42 803.976 l 24 762 m 0.023987 762 l 546 780 m 546 803.976 l 564 762 m 587.976 762 l 42 24 m 42 0.023987 l 24 42 m 0.023987 42 l 546 24 m 546 0.023987 l 564 42 m 587.976 42 l S 0 G 0.25 w 42 780 m 42 803.976 l 24 762 m 0.023987 762 l 546 780 m 546 803.976 l 564 762 m 587.976 762 l 42 24 m 42 0.023987 l 24 42 m 0.023987 42 l 546 24 m 546 0.023987 l 564 42 m 587.976 42 l S 1 G 0.5 w 270 792 m 318 792 l 270 12 m 318 12 l 12 426 m 12 378 l 576 426 m 576 378 l 294 804 m 294 780 l 294 24 m 294 0 l 0 402 m 24 402 l 564 402 m 588 402 l 294 792 m 300 792 l 300 788.688 297.312 786 294 786 c 290.688 786 288 788.688 288 792 c 288 795.312 290.688 798 294 798 c 297.312 798 300 795.312 300 792 c 294 12 m 300 12 l 300 8.688 297.312 6 294 6 c 290.688 6 288 8.688 288 12 c 288 15.312 290.688 18 294 18 c 297.312 18 300 15.312 300 12 c 12 402 m 18 402 l 18 398.688 15.312 396 12 396 c 8.688 396 6 398.688 6 402 c 6 405.312 8.688 408 12 408 c 15.312 408 18 405.312 18 402 c 576 402 m 582 402 l 582 398.688 579.312 396 576 396 c 572.688 396 570 398.688 570 402 c 570 405.312 572.688 408 576 408 c 579.312 408 582 405.312 582 402 c S 0 G 0.25 w 270 792 m 318 792 l 270 12 m 318 12 l 12 426 m 12 378 l 576 426 m 576 378 l 294 804 m 294 780 l 294 24 m 294 0 l 0 402 m 24 402 l 564 402 m 588 402 l 294 792 m 300 792 l 300 788.688 297.312 786 294 786 c 290.688 786 288 788.688 288 792 c 288 795.312 290.688 798 294 798 c 297.312 798 300 795.312 300 792 c 294 12 m 300 12 l 300 8.688 297.312 6 294 6 c 290.688 6 288 8.688 288 12 c 288 15.312 290.688 18 294 18 c 297.312 18 300 15.312 300 12 c 12 402 m 18 402 l 18 398.688 15.312 396 12 396 c 8.688 396 6 398.688 6 402 c 6 405.312 8.688 408 12 408 c 15.312 408 18 405.312 18 402 c 576 402 m 582 402 l 582 398.688 579.312 396 576 396 c 572.688 396 570 398.688 570 402 c 570 405.312 572.688 408 576 408 c 579.312 408 582 405.312 582 402 c S Q endstream endobj 179 0 obj<>/ExtGState<>>> endobj 182 0 obj<>stream q 1 i 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n 1 g /GS2 gs 87 696 387 12 re f BT /F6 1 Tf 10 0 0 10 87 700.7319 Tm 0.017 g 0 Tc 0 Tw (38)Tj /F8 1 Tf 11.0033 0 TD 0.1514 Tc -0.0003 Tw ( \012)Tj /F6 1 Tf 7.6614 0 TD -0.0005 Tc 0.0003 Tw [(| )-253.2(V)98.7(a)8.6(r)-6.2(i)-3.3(a)7.6(b)11.9(ili)11.9(t)-3.4(y a)8.6(n)3.8(d I)38.7(ts M)25.7(e)-6.2(asur)12.8(emen)18.7(t)]TJ ET 0.902 g 132 284.981 342 399.019 re f BT 11 0 0 11 156 664.0051 Tm 0.017 g -0.005 Tc -0.0004 Tw [(T)82.9(r)-0.1(acin)8(g t)-6(h)4(e tra)8.9(n)8(smissio)12.2(n o)12.2(f)-0.1( a)-5.1(l)-5(leles f)-9.9(r)13.1(o)12.2(m)-0.1( t)-6(h)4(es)-8(e tw)8(o p)12.1(r)13.1(og)8.1(en)23.1(y indi)7.1(vid)12.2(u)-3.1(a)-5.1(l)3(s,)]TJ -1.0909 -1.1818 TD -0.0326 Tw [(let t)-6(h)4(er)13.1(e b)-8.8(e)0( )]TJ /F3 1 Tf 4.4921 0 TD 0 Tc 0 Tw (n)Tj 7.7 0 0 6.6 199.2122 647.3751 Tm (i)Tj /F6 1 Tf 11 0 0 11 203.3602 651.0051 Tm -0.0042 Tc -0.0334 Tw [( 1 f)-5.2(u)0.6(r)-9(t)-5.2(her links in t)-5.2(h)4.8(e pa)19.7(t)-5.2(h)0.7( co)13(nnec)-6.1(tin)8.8(g)0.8( )]TJ /F3 1 Tf 15.4685 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 380.7632 647.3751 Tm (i)Tj /F6 1 Tf 11 0 0 11 384.9113 651.0051 Tm -0.011 Tc [(to)-6( )]TJ /F3 1 Tf 0.9884 0 TD 0 Tc (C)Tj /F6 1 Tf 0.8194 0 TD -0.0115 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.6755 0 TD 0 Tc (D)Tj /F6 1 Tf 0.703 0 TD -0.005 Tc -0.0326 Tw [(, w)-6.9(h)4(er)13.1(e)]TJ /F3 1 Tf -26.0872 -1.1818 TD 0 Tc 0 Tw (n)Tj 7.7 0 0 6.6 149.7994 634.3751 Tm (i)Tj /F6 1 Tf 11 0 0 11 154.1515 638.0051 Tm -0.0049 Tc -0.0142 Tw [(is t)-5.9(h)4.1(e t)6.1(o)11.4(t)-5.9(a)-5(l n)19.1(u)-0.1(m)10.1(b)-8.7(er o)12.3(f)0( indi)7.2(vid)12.3(u)-3(a)-5(l)3.1(s in t)-5.9(h)4.1(e pa)19(t)-5.9(h)0(, inc)6.1(l)12.2(udin)8.1(g )]TJ /F3 1 Tf 21.8697 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 401.9676 634.3751 Tm (i)Tj /F6 1 Tf 11 0 0 11 404.0326 638.0051 Tm -0.005 Tc (, )Tj /F3 1 Tf 0.4309 0 TD 0 Tc (C)Tj /F6 1 Tf 0.63 0 TD -0.005 Tc -0.0141 Tw [(, a)8.9(n)4.1(d )]TJ /F3 1 Tf 2.1249 0 TD 0 Tc 0 Tw (D)Tj /F6 1 Tf 0.703 0 TD -0.005 Tc -0.0141 Tw [(. A)40.9(t)]TJ -27.5281 -1.1818 TD 0.0044 Tc 0.0802 Tw [(e)-6.1(a)-0.4(c)5.8(h)-0.3( o)12(f)-0.3( t)-6.2(h)3.8(es)-8.2(e links, t)-6.2(h)3.8(er)12.9(e is a p)11.9(r)12.9(o)5(b)-5.1(a)7.7(b)12(ili)12(t)-3.3(y o)12(f)-0.3( o)12(n)3.9(e-ha)-5.3(lf o)12(f)-0.3( ha)8.7(ndin)7.8(g o)12(n)-0.3( a)8.7(n)]TJ T* -0.0042 Tc -0.0008 Tw [(allele inher)-5.4(i)12.7(t)6.5(e)-4.4(d f)-9.3(r)13.7(o)12.8(m)0.5( )]TJ /F3 1 Tf 8.2756 0 TD 0 Tc 0 Tw (A)Tj 7.7 0 0 6.6 242.284 608.3751 Tm (i)Tj /F6 1 Tf 11 0 0 11 244.3511 612.0051 Tm -0.0044 Tc -0.0006 Tw [(. The net p)12.4(r)13.5(o)5.5(b)-4.6(a)8.2(b)12.5(ili)12.5(t)-2.7(y t)-5.7(h)3.4(a)19.2(t)0.2( a)9.2(n)0.3( allele s)-5.7(a)9.2(m)19.3(p)7.3(led f)-9.5(r)13.5(o)12.6(m)0.3( )]TJ /F3 1 Tf 19.1514 0 TD 0 Tc 0 Tw (C)Tj /F6 1 Tf -28.2742 -1.1818 TD -0.0032 Tc -0.0018 Tw [(is iden)19.8(tical wi)13(t)-5.1(h)0.7( o)13.1(n)4.9(e f)-9(r)14(o)13.1(m)0.8( )]TJ /F3 1 Tf 10.3384 0 TD 0 Tc 0 Tw (D)Tj /F6 1 Tf 0.7039 0 TD -0.0042 Tc -0.0008 Tw [(, as a r)13(e)-0.2(s)4.8(u)-5.2(l)11.9(t)-0.3( o)12.1(f)-0.3( tra)8.7(n)7.8(smis)4.8(sio)12.1(n)-0.2( do)16(wn t)-6.1(h)-0.3(is pa)18.7(t)-6.1(h)-0.3(, is)]TJ -11.0424 -1.1818 TD 0.001 Tc 0 Tw [(th)24.9(u)9(s)5.9(:)]TJ 0 -4.9093 TD 0.0047 Tc -0.0079 Tw [(The co)-8.7(ef)-9.8(f)-9.8(i)0.1(cien)19.1(t o)12.3(f)0( kin)8.1(s)4.1(hi)12.3(p o)12.3(f)0( )]TJ /F3 1 Tf 11.5738 0 TD 0 Tc 0 Tw (C)Tj /F6 1 Tf 0.8633 0 TD -0.0019 Tc [(and)-6.5( )]TJ /F3 1 Tf 1.7387 0 TD 0 Tc (D)Tj /F6 1 Tf 0.9363 0 TD -0.0053 Tc 0.0021 Tw [(c)-12.9(a)-1(n)-10( b)-18.7(e)-9.9( fou)-10.1(n)-5.8(d)-9.9( f)-19.8(r)3.2(om)-10( t)-15.9(h)-10(i)-6.8(s)-10( for)-15.8(m)9.1(u)-15(l)-13(a)-10.1( b)6.2(y)]TJ -15.1121 -1.1818 TD 0.0046 Tc 0.0699 Tw [(addin)8(g u)12(p)-0.1( t)-6(h)4(e co)12.2(n)19(t)-5(r)-5.9(i)4.1(b)11.2(u)12(tio)12.2(n)8(s f)-9.9(r)13.1(o)12.2(m)-0.1( a)-5.1(l)-5(l p)-8.9(o)0(ssib)7.1(le m)19(u)12(t)9.9(u)-3.1(a)-5.1(l)-5(l)6.9(y)-0.2( ex)7.9(c)6(l)12.1(usi)7.1(v)8(e pa)18.9(t)-6(h)7.9(s)]TJ T* -0.0056 Tc -0.0221 Tw [(le)-6.5(adin)7.4(g f)-10.5(r)12.5(o)11.6(m)-0.7( t)-6.6(h)3.4(e co)11.6(mmo)11.6(n)-0.7( a)8.3(n)3.5(ces)4.4(t)5.4(o)11.6(r)5.5(s, as sho)15.5(wn in )]TJ /F1 1 Tf 19.3521 0 TD -0.0039 Tc -0.023 Tw [(E)-16.5(q)12.4(ua)16.4(t)6.4(i)-4.7(o)11.2(n)1.2( B1.4.1)]TJ /F6 1 Tf 6.6131 0 TD 0 Tc 0 Tw (:)Tj -0.1978 -2.5911 TD -0.0049 Tc (\(B1.4.1\))Tj -24.6765 -2.6818 TD 0.0034 Tc -0.0084 Tw [(A simila)9.7(r r)13.9(e)0.8(s)5.8(u)-4.3(l)12.9(t)0.7( ca)9.7(n b)-8(e)0.8( o)6(b)12(t)-5.2(a)9.7(ined f)9.7(o)13.1(r a)9.7(n)0.7( X-link)9.8(ed lo)-7.9(c)-6.1(u)3.8(s \(wi)13(t)-5.2(h male het-)]TJ -1.0909 -1.1818 TD -0.0057 Tc -0.028 Tw [(er)12.4(oga)8.2(mety\) b)15.4(y)-0.9( no)10.6(tin)7.3(g)-0.7( t)-6.7(h)2.3(a)18.2(t)-0.8( ma)-5.8(les ha)17.2(v)7.3(e)-0.7( o)11.5(n)-5.7(l)6.2(y)-0.9( o)11.5(n)3.4(e X c)5.3(h)-0.8(r)12.4(o)11.5(mos)-8.7(o)11.5(me)5.4(, a)8.2(n)3.4(d t)-6.7(h)3.3(er)12.4(e-)]TJ T* 0.0059 Tc 0.0616 Tw [(f)10.2(o)13.5(r)14.4(e)1.3( tra)10.2(n)9.3(smi)13.5(t a gi)8.4(v)9.3(e)1.3(n allele wi)13.5(t)-4.7(h)1.2( p)13.4(r)14.4(o)6.5(b)-3.6(a)9.2(b)13.5(ili)13.5(t)-1.8(y o)13.5(n)5.4(e)7.4(,)1.3( s)-6.7(o)1.3( t)-4.7(h)4.3(a)20.2(t)1.2( a co)13.5(n)20.3(t)-3.7(r)-4.6(i)5.4(b)12.5(u)13.3(tio)13.5(n)]TJ T* -0.0038 Tc -0.0012 Tw [(f)-9.8(r)13.2(o)12.4(m)0.1( a male t)6.1(o)0.1( his da)19(ug)-6.7(h)19(t)6.1(er is no)11.4(t dis)-7.8(c)0.1(o)11.4(u)-0.1(n)19.1(t)6.1(ed b)16.2(y)-0.1( o)12.4(n)4.2(e-half)5.1(. P)22.1(a)19(t)-5.9(h)8(s wi)12.3(t)-5.9(h)0( tw)8.2(o)]TJ T* -0.0053 Tc -0.0259 Tw [(s)4.7(u)-0.5(cces)4.7(s)-0.4(i)6.8(v)7.7(e males a)8.6(r)12.8(e igno)11.9(r)12.8(e)-5.2(d)5.8(,)-0.3( since males do no)11(t tra)8.6(n)7.7(smi)11.9(t X c)5.7(h)-0.4(r)12.8(o)11.9(mos)-8.3(o)11.9(mes)]TJ T* -0.0047 Tc -0.0003 Tw [(t)5.5(o)-0.4( t)-6.5(h)3.5(eir s)-8.4(o)11.8(n)7.5(s)-0.6(. T)82.4(r)-0.5(a)8.4(n)7.5(smissio)11.8(n)-0.6( t)-6.5(h)-0.6(r)12.7(o)10.8(ug)-7.3(h f)8.5(e)-0.5(males is t)-6.5(h)3.5(e s)-6.5(a)8.4(me as f)8.5(o)11.8(r t)-6.5(h)3.5(e a)18.4(u)11.5(t)5.5(o)-0.4(s)-8.4(o)-0.5(-)]TJ T* 0.0046 Tc 0.0172 Tw [(ma)-5.1(l cas)-8(e)6.1(, a)8.9(n)4.1(d s)-8(o)0( t)-6(h)4(e n)19(u)-0.2(m)10(b)-8.8(er)6(s o)12.2(f)-0.1( f)8.9(e)0(ma)-5.1(les in t)-6(h)4(e pa)18.9(t)-6(h)7.9(s a)8.9(r)13.1(e co)11.3(un)19(t)6(e)-4.9(d in t)-6(h)4(e)]TJ T* -0.0059 Tw [(s)-5.9(a)9(me wa)18(y as f)9(o)12.3(r t)-5.9(h)4.1(e a)19(u)12.1(t)6.1(o)0.1(s)-7.9(o)12.3(mal cas)-7.9(e)6.2(. M)17.1(a)-5(les a)9(n)4.2(d f)9(e)0.1(males a)9(r)13.2(e in)19.1(t)6.1(e)0.1(r)13.2(c)6.1(ha)9(n)8.1(g)8.2(ed)]TJ T* -0.0054 Tc -0.0223 Tw [(f)8.5(o)11.8(r t)-6.4(h)3.6(e cas)-8.4(e)-0.4( o)11.8(f)-0.5( f)8.5(e)-0.4(ma)-5.5(le het)5.6(e)-0.4(r)12.7(oga)8.5(mety)72.4(.)]TJ 1.0909 -1.1818 TD 0.0048 Tc 0.0199 Tw [(F)19.2(o)12.4(r f)-5.8(u)0(r)-9.6(t)-5.8(her det)-5.8(a)9.1(i)-4.7(ls o)12.4(n)0.1( in)10.1(b)12.4(r)13.3(eedin)8.2(g in p)-8.7(e)-4.7(digr)13.3(e)-4.7(es, s)-7.8(e)-4.7(e Cr)13.3(o)16.3(w)0.2( a)9.1(n)4.3(d K)7.2(i)0.2(m)19.2(u)0(ra)]TJ -1.0909 -1.1818 TD -0.0002 Tc -0.0048 Tw [(\(1970, Cha)19(p)11.2(t)6.1(er 3\), N)26.1(a)5.1(g)-23.8(y)-6.9(laki \(1992, Cha)19(p)11.2(t)6.1(er 9\), a)9(n)4.2(d F)20.1(a)-4.9(lco)12.4(n)4.2(er a)9(n)4.2(d M)17.1(a)0(c)6.2(k)0.1(a)18(y)]TJ T* -0.0047 Tc -0.023 Tw [(\(1996, Cha)19.2(p)11.4(t)6.3(e)0.3(r 5\).)]TJ ET Q q 1 i 266.5 496.5 97 -29 re 222.118 305 m W* n 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n 0 G 0 J 0 j 0.375 w 10 M []0 d /GS2 gs 312.625 481.219 m 316.281 481.219 l S BT /F3 1 Tf 11 0 0 11 270.0938 479.4999 Tm 0 g 6.8313 Tc 0 Tw (ff)Tj 6.375 0 0 6.375 272.7188 475.9687 Tm 0.0317 Tc (CD)Tj 7.3382 1.8922 TD 0 Tc (n)Tj 4.9951 -1.8922 TD (A)Tj -7.7549 -0.9314 TD (i)Tj 4.5937 0 0 4.5937 322.3125 485.8749 Tm (i)Tj 7.0748 -2.6259 TD (i)Tj /F17 1 Tf 11 0 0 11 287.2188 479.4999 Tm (=)Tj 11 0 0 19.184 308.6563 477.9999 Tm (\()Tj 11 0 0 19.624 316.5938 477.7812 Tm (\))Tj 11 0 0 11 336.6875 479.4999 Tm (+)Tj 11 0 0 22.055 325.7188 477.0937 Tm (\()Tj 11 0 0 22.561 357.7188 477.2187 Tm (\))Tj 14.2813 0 0 14.2813 297.75 477.8749 Tm ()Tj /F6 1 Tf 6.375 0 0 6.375 312.875 483.6249 Tm (1)Tj 0.0196 -1.3578 TD (2)Tj 11 0 0 11 328.5625 479.4999 Tm (1)Tj ET Q q 1 i 286.5 576.503 57 -25 re 222.118 305 m W* n 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n 0 G 0 J 0 j 0.5 w 10 M []0 d /GS2 gs 291.781 563.472 m 296.187 563.472 l S BT /F6 1 Tf 6.375 0 0 6.375 292.4062 564.9717 Tm 0 g 0 Tc 0 Tw (1)Tj 0.0196 -1.1471 TD (2)Tj 11 0 0 11 308.4687 560.503 Tm (1)Tj /F17 1 Tf 11 0 0 17.248 287.8125 559.4717 Tm (\()Tj 11 0 0 17.655 296.5 559.3467 Tm (\))Tj 11 0 0 11 316.5938 560.503 Tm (+)Tj 11 0 0 22.055 305.625 558.0967 Tm (\()Tj 11 0 0 22.561 337.625 558.2217 Tm (\))Tj /F3 1 Tf 6.375 0 0 6.375 299.4063 568.2217 Tm (n)Tj 4.9951 -1.7647 TD (A)Tj 4.5937 0 0 4.5937 302.2187 566.0655 Tm (i)Tj 7.0748 -2.449 TD (i)Tj 11 0 0 11 328.125 560.503 Tm (f)Tj ET Q q 1 i 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n /GS2 gs BT /F6 1 Tf 11 0 0 11 144 247.2072 Tm 0.017 g 0.0042 Tc 0.3078 Tw [(The e)-6.3(a)8.5(rliest indi)6.7(vid)11.8(u)-3.5(a)-5.5(l)2.6(s f)8.5(o)11.8(r w)-7.3(h)-0.5(ic)5.6(h w)7.6(e)-0.4( ha)17.5(v)7.6(e)-0.4( p)-9.3(e)-5.3(digr)12.7(e)-5.3(e inf)8.5(o)11.8(r)-6.3(m)2.7(a)18.5(t)-5.4(io)11.8(n a)8.5(r)12.7(e)]TJ -1.0909 -1.1818 TD 0.0046 Tc -0.0091 Tw [(des)-8(cended f)-9.9(r)13.1(o)12.2(m)-0.1( indi)7.1(vid)12.2(u)-3.1(a)-5.1(l)3(s t)-6(h)3(a)18.9(t)-0.1( w)8(e)0(r)13.1(e)0( mem)10(b)-8.8(er)6(s o)12.2(f)-0.1( t)-6(h)4(e p)-8.9(o)11.3(p)11.1(u)-5.1(la)18.9(tio)12.2(n)-0.1(, b)11.2(u)12(t a)8.9(r)13.1(e no)11.3(t)]TJ T* 0.0053 Tc 0.0017 Tw [(t)-5.3(h)4.7(em)8.7(s)-7.3(e)4.8(l)7.6(v)8.7(es r)13.8(e)0.7(p)12.8(r)13.8(es)-7.3(en)19.7(t)6.7(e)-4.2(d in t)-5.3(h)4.7(e p)-8.2(e)-4.2(digr)13.8(e)-4.2(e)6.8(.)0.7( T)98.7(o)0.7( de)-5.2(a)-4.4(l)0.6( wi)12.9(t)-5.3(h)0.6( suc)6.7(h)0.6( unkno)16.8(w)-2.2(n a)9.6(n)4.8(cestr)-28.2(y)73.5(,)]TJ T* 0.0054 Tc 0.0421 Tw [(w)8.8(e)0.8( ca)9.7(n def)-9.1(ine a)9.7(n)0.7( ini)13(t)-4.2(ial g)8.9(e)0.8(nera)19.7(tio)13(n)0.7( o)13(f)0.7( t)-5.2(h)4.8(e p)-8.1(o)12.1(p)11.9(u)-4.3(la)19.7(tio)13(n)0.7( f)9.7(o)13(r w)-6.1(h)0.7(ic)6.8(h all alleles a)9.7(r)13.9(e)]TJ T* -0.0044 Tc 0 Tw [(co)12.8(n)8.6(s)0.5(ider)13.7(ed )]TJ /F3 1 Tf 4.5232 0 TD -0.0119 Tc [(no)5.1(t)]TJ /F6 1 Tf 1.4846 0 TD -0.005 Tc -0.0127 Tw [(t)6(o)0( b)-8.8(e)0( i)6.1(.)0(b)29(.)0(d)6.1(., i)6.1(.)0(e)6.1(., f)8.9(o)12.2(r w)-6.9(h)-0.1(ic)6(h )]TJ /F3 1 Tf 10.0274 0 TD 0 Tc 0 Tw (f)Tj /F6 1 Tf 0.4756 0 TD -0.0044 Tc -0.0133 Tw [(= 0. 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This is called t)-5.3(h)4.7(e )]TJ /F3 1 Tf 25.312 0 TD 0.0111 Tc 0.032 Tw [(fi)6.4(xa)28.6(t)15.5(i)10.5(o)16.4(n)6.3( i)19.6(n)13.4(d)10.7(e)6.4(x)]TJ /F6 1 Tf 5.5512 0 TD 0 Tc 0 Tw (,)Tj -30.8631 -1.1818 TD -0.0049 Tc -0.0242 Tw [(o)12.3(f)-5.9(t)6.1(e)0.1(n deno)11.4(t)6.1(ed b)16.2(y)-0.1( )]TJ /F3 1 Tf 6.7972 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.7199 0 TD -0.0055 Tc -0.0236 Tw [(in o)11.7(r)12.6(der t)5.5(o)-0.5( distin)7.5(guish i)11.7(t)-0.6( f)-10.4(r)12.6(o)11.7(m)-0.6( t)-6.5(h)3.5(e mo)11.7(r)12.6(e)-0.5( r)12.6(e)-0.5(str)-6.4(i)-0.5(c)-7.4(t)5.5(ed co)11.7(ncep)10.6(t o)11.7(f)]TJ -7.5171 -1.1818 TD 0.0061 Tc 0.128 Tw [(iden)20.5(ti)13.7(ty p)13.6(r)14.6(o)6.7(b)-3.4(a)9.4(b)13.7(ili)13.7(t)-1.6(y \(s)-6.5(ee )]TJ /F1 1 Tf 10.211 0 TD 0.0045 Tc 0.1233 Tw [(S)-12.4(e)-13.2(c)-6.2(t)4.8(i)-6.3(o)9.6(n 7.1.i.a)]TJ /F6 1 Tf 6.0438 0 TD 0.0063 Tc 0.1278 Tw [(\). P)33.7(o)1.7(si)13.9(ti)8.8(v)9.7(e)1.7( )]TJ /F3 1 Tf 4.4573 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.8928 0 TD 0.0043 Tc 0.1298 Tw [(r)12.8(e)-0.3(p)11.8(r)12.8(es)-8.3(en)18.7(ts a)8.6(n)-0.4( ex)7.6(cess o)11.9(f)]TJ -21.6049 -1.1818 TD 0.0042 Tc 0.0012 Tw [(ho)11.8(mo)5.7(zyg)7.7(o)10.9(t)5.6(e)-0.4(s o)15.7(v)7.6(er t)-6.4(h)3.6(e ra)8.5(ndo)11.8(m)-0.5(-ma)18.5(t)-5.4(in)7.6(g exp)-9.3(e)-5.3(c)-7.3(t)-6.4(a)18.5(t)-5.4(io)11.8(n, a)8.5(n)3.7(d nega)18.5(ti)6.7(v)7.6(e)-0.4( )]TJ /F3 1 Tf 26.2078 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.764 0 TD 0.0046 Tc [(r)13.1(e)0(p)12.1(r)13.1(es)-8(en)19(ts)]TJ -26.9717 -1.1818 TD -0.0108 Tc -0.0169 Tw [(he)-5.8(te)-5.8(r)7.3(o)0.3(z)-5.9(y)-6(go)5.5(te)-5.8( e)-5.8(x)2.1(c)-5.9(e)-5.8(ss)-5.9(.)]TJ 1.0909 -1.1818 TD -0.0051 Tc -0.0192 Tw [(I)38.9(t)-0.2( is o)5.1(b)16(vio)11.2(u)2.9(s t)-6.1(h)2.9(a)18.8(t)-0.2( in)9.8(b)12.1(r)13(eedin)7.9(g g)8(e)-0.1(nera)18.8(t)5.9(e)-0.1(s a)8.8(n)-0.2( ex)7.8(ces)4.9(s)-0.2( o)12.1(f)-0.2( ho)12.1(mo)6(zyg)8(o)11.2(t)5.9(e)-0.1(s in a p)-9(o)11.2(p)11(u)-5.2(la-)]TJ -1.0909 -1.1818 TD 0.0054 Tc 0.1719 Tw [(tio)13(n)0.7(, wi)13(t)-5.2(h)0.7( a maxim)19.8(u)0.6(m val)12.9(u)0.6(e o)13(f)0.7( )]TJ /F3 1 Tf 13.6588 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.9359 0 TD 0.0037 Tc 0.1736 Tw [(= 1. I)38.1(t)-1( is im)18.1(p)-9.8(o)11.3(r)-10.7(t)-6.9(a)8(n)18.1(t t)5.1(o)-0.9( under)5.1(st)-6.9(a)8(n)3.2(d t)-6.9(h)2.1(a)18(t)]TJ -14.5948 -1.1818 TD -0.0006 Tc -0.0044 Tw [(ho)9.5(mozygosi)9.5(t)-5.8(y)-2.9( is no)8.5(t t)-8.7(h)1.3(e s)-8.7(a)6.1(me)]TJ 11.8127 0 TD 0.002 Tc -0.007 Tw [( as a)8.7(n)-0.2( a)7.8(b)-0.1(s)-8.1(e)-0.1(nce o)12.1(f)-0.2( g)8(e)-0.1(netic di)6.9(v)7.8(e)-0.1(r)5.9(s)-0.3(i)12.1(t)-3.2(y in t)-6.1(h)3.9(e p)-9(o)11.1(p)11(u)-5.2(la-)]TJ -11.8127 -1.1818 TD 0.0029 Tc 0 Tw [(tio)14.8(n)2.5(.)2.6( )]TJ /F1 1 Tf 2.0746 0 TD 0.0182 Tc -0.0234 Tw [(Eq)29(u)13.8(a)33(t)22.9(i)11.9(o)27.7(n)17.7( 1)17.6(.)17.7(3)]TJ /F6 1 Tf 5.5421 0 TD -0.0055 Tc 0.0005 Tw [(sho)10.3(w)-5.9(s)-6( t)-11.8(h)-2.8(a)13(t)-6( i)6.3(t)-6( is)-6( qu)-6(i)6.3(t)0.1(e)-5.8( p)-14.8(o)-5.8(ss)-6(ibl)-6(e)-5.8( fo)6.4(r)-5.9( h)-6(i)-5.9(g)-12.7(h)-10.9(ly)-6( i)-5.9(n)4.1(b)6.4(r)7.3(e)-10.7(d)-5.9( p)-14.8(o)5.4(p)5.3(u)-10.9(l)-8.9(a)13(t)-10.9(i)-5.9(o)6.4(n)2.1(s)]TJ -7.6166 -1.1818 TD -0.0124 Tc -0.0153 Tw [(to)-7.4( ha)10.5(ve)-7.4( non)-7.5(z)-7.5(e)-7.4(r)5.7(o)-7.4( d)-7.4(i)-0.3(ve)-7.4(rs)-7.5(it)-10.5(y)-7.6( \()]TJ /F1 1 Tf 10.3945 0 TD -0.0153 Tc -0.0116 Tw [(Pro)-3.1(b)-7.1(l)-16(e)-4.9(m)-10.1( 1)-10.3(.)-10.2(5)]TJ /F6 1 Tf 4.9832 0 TD -0.0048 Tc 0 Tw (\).)Tj -14.2868 -1.1818 TD 0.005 Tc 0.143 Tw [(P)32.4(o)0.4(si)12.6(ti)7.5(v)8.4(e)0.4( ass)-7.6(o)12.6(r)-9.4(t)-5.6(a)19.3(t)-4.6(i)7.5(v)8.4(e ma)19.3(tin)8.4(g)0.4( \(i)6.5(.e)6.5(., p)12.5(r)13.5(ef)9.3(er)13.5(en)19.4(tia)-4.7(l)0.3( ma)19.3(tin)8.4(g)0.4( b)-8.4(e)0.4(tw)8.4(een indi)7.5(vid)12.6(u)-2.7(a)-4.7(l)3.4(s)]TJ -1.0909 -1.1818 TD -0.0045 Tc -0.0005 Tw [(wi)12.1(t)-6.1(h)-0.2( simila)8.8(r g)8(e)-0.1(no)11.2(typ)-9(e)-0.1(s\) als)-8.1(o)-0.1( g)8(e)-0.1(nera)18.8(t)5.9(e)-0.1(s ho)12.1(mo)6(zyg)8(o)11.2(t)5.9(e)-0.1( ex)7.8(ces)4.9(s)-0.3(, b)11.1(u)11.9(t t)-6.1(h)-0.2(is is ca)18.8(us)-8.1(ed b)16(y)]TJ T* 0.0051 Tc 0.1053 Tw [(iden)19.5(ti)12.7(ty in st)-5.5(a)19.4(t)6.5(e o)12.7(f)0.4( a)-4.6(l)-4.5(leles, a)9.4(n)4.6(d no)11.8(t dir)13.6(ec)-6.4(t)-5.5(l)7.4(y b)16.6(y)0.3( iden)19.5(ti)12.7(ty b)16.6(y)0.3( des)-7.5(cen)19.5(t)0.4(. N)25.5(ega)19.4(ti)7.6(v)8.5(e)]TJ T* -0.0053 Tc -0.0091 Tw [(ass)-8.3(o)11.9(r)-10.1(t)-6.3(a)18.6(t)-5.3(i)6.8(v)7.7(e ma)18.6(tin)7.7(g)-0.3( has t)-6.3(h)3.7(e o)11(p)10.8(p)-9.2(o)-0.3(si)11.9(t)5.7(e)-0.3( ef)-10.2(f)8.6(e)-5.2(c)-7.2(t)-0.4(. W)96.7(e)-0.3( do no)11(t de)-6.2(a)-5.4(l)-0.4( wi)11.9(t)-6.3(h)-0.4( t)-6.3(h)3.7(e det)-6.3(a)8.6(i)-5.2(led t)-6.3(h)3.7(e-)]TJ T* 0.0037 Tc -0.0087 Tw [(o)12.2(r)-28.9(y o)12.2(f)-0.2( as)4.9(s)-8(o)12.2(r)-9.9(t)-6(a)18.8(t)-5.1(i)7(v)7.9(e ma)18.8(tin)7.9(g)0( in t)-6(h)-0.2(is b)-8.9(o)-8.8(o)7.1(k)-0.1( \(s)-8(ee Cr)13.1(o)16.1(w)-0.1( a)8.8(n)4(d K)7(i)-0.1(m)18.9(u)-0.3(ra 1970, Cha)18.8(p)11.1(t)5.9(er 4;)]TJ T* 0.0048 Tc 0.0984 Tw [(B)7.2(u)-4.9(lmer 1980, Cha)19.1(p)11.3(t)6.2(e)0.2(r 8; N)26.2(a)5.2(g)-23.7(y)-6.8(laki 1992, Cha)19.1(p)11.3(t)6.2(e)0.2(r)6.2(s)0.1( 5 a)9.1(n)4.3(d 10\). H)25.3(o)16.3(w)8.2(e)-7.6(v)8.2(e)0.2(r)63.4(,)0.2( i)12.4(t)0.1( is)]TJ T* 0.0052 Tc 0.0055 Tw [(w)8.6(o)12.8(r)-9.2(t)-5.4(h p)-8.3(o)12.8(in)19.6(tin)8.6(g)0.6( o)11.9(u)12.6(t a)9.5(n)0.5( im)19.6(p)-8.3(o)12.8(r)-9.2(t)-5.4(a)9.5(n)19.6(t dif)-9.3(f)9.5(e)0.6(r)13.7(e)0.6(nce b)-8.2(e)0.6(tw)8.6(een t)-5.4(h)4.6(e ef)-9.3(f)9.5(e)-4.3(c)-6.3(ts o)12.8(f)0.5( in)10.5(b)12.8(r)13.7(eedin)8.6(g)]TJ T* -0.0013 Tc -0.0037 Tw [(a)8.7(n)3.9(d ass)-8.1(o)12.1(r)-10(t)-6.1(a)18.7(t)-5.2(i)6.9(v)7.8(e ma)18.7(tin)7.8(g; in)9.8(b)12(r)13(eedin)7.8(g le)-6(a)17.7(v)7.8(es allele f)-10(r)13(eq)9.7(uencies unc)5.9(h)2.9(a)8.7(n)7.8(g)7.9(e)-5(d)5.9(,)-0.1( s)-8.1(o)-0.1( t)-6.1(h)2.9(a)18.7(t)]TJ T* 0.004 Tc -0.0043 Tw [(a c)5.4(h)2.4(a)8.3(n)7.4(g)7.5(e)-0.6( in t)-6.6(h)3.4(e ma)18.3(tin)7.4(g)-0.6( syst)5.4(em t)5.4(o)-0.6( a hig)-7.4(h)3.4(er f)-10.5(r)12.5(eq)9.2(uenc)-16.5(y o)11.6(f)-0.7( ma)18.3(tin)7.4(g)-0.6(s b)-9.4(e)-0.6(tw)7.4(een r)12.5(e)3.5(la-)]TJ T* -0.0043 Tc -0.0297 Tw [(ti)7.8(v)8.7(e)0.7(s sim)19.7(p)7.7(l)7.6(y)0.5( incr)13.8(e)-5.2(a)3.7(s)-7.3(e)0.7(s t)-5.3(h)4.7(e val)12.8(u)0.5(e o)12.9(f)0.6( )]TJ /F3 1 Tf 13.2739 0 TD 0 Tc 0 Tw (F)Tj /F6 1 Tf 0.5221 0 TD -0.0049 Tc -0.0291 Tw [(, i)6.2(.)0.1(e)6.2(., i)12.3(t)0( c)6.1(h)3.1(a)9(n)8.1(g)8.2(e)0.1(s t)-5.9(h)4.1(e g)8.2(e)0.1(no)11.4(typ)-8.8(e)0.1( f)-9.8(r)13.2(eq)9.9(uencies b)11.3(u)12.1(t)]TJ -13.796 -1.1818 TD -0.0012 Tc -0.0038 Tw [(no)11.3(t t)-6(h)4(e allele f)-9.9(r)13.1(eq)9.8(uencies. A)16(s)5(s)-7.9(o)12.3(r)-9.8(t)-6(a)18.9(t)-5(i)7.1(v)8(e ma)18.9(tin)8(g)-2.9(, ho)16.2(w)8.1(e)-7.8(v)8(e)0(r)63.2(,)0( ca)8.9(n a)8.9(f)-9.9(f)8.9(e)-4.9(c)-6.9(t)-0.1( t)-6(h)4(e f)8.9(e)0(r)-9.8(t)-5(ili)12.2(t)-5(ies)]TJ T* 0.0043 Tc 0.0731 Tw [(o)11.9(f)-0.4( dif)-10.2(f)8.6(e)-0.3(r)12.8(e)-0.3(n)18.7(t)-0.4( g)7.8(e)-0.3(no)11(typ)-9.2(e)-0.3(s, a)8.6(n)3.8(d ma)17.6(y t)-6.3(h)18.6(us ac)-7.2(t as a f)8.6(o)11.9(r)-6.2(m)-0.4( o)11.9(f)-0.4( s)-8.3(e)3.8(lec)-7.2(t)-5.3(io)11.9(n t)-6.3(h)2.7(a)18.6(t)-0.4( c)5.7(h)2.7(a)8.6(n)7.7(g)7.8(e)-0.3(s)]TJ T* -0.0042 Tc -0.0235 Tw [(allele f)-9.1(r)13.9(eq)10.6(uencies.)]TJ /F1 1 Tf 8.6382 -1.7727 TD 0.0495 Tc 0 Tw [(1.3.ii.c)-8.2(.)]TJ /F3 1 Tf 3.711 0 TD -0.0014 Tc 0.0014 Tw [(Re)7.7(g)-7.2(u)3.8(la)14.7(r s)6.7(y)-1.3(s)8.7(t)8.7(ems o)9.9(f)-1.4( m)5.8(a)20.8(t)7.7(i)11.8(n)11.8(g)]TJ /F6 1 Tf -12.3492 -1.1818 TD -0.0019 Tc -0.0031 Tw [(I)16.3(n)0.1( s)-7.8(o)12.4(me sim)19.2(p)7.1(le cas)-7.8(e)0.2(s, t)-5.8(h)4.2(e in)10.1(b)12.4(r)13.3(eedin)8.1(g co)-8.6(ef)-9.7(f)-9.7(icien)19.1(t)0( ca)9(n b)-8.6(e)0.2( calc)-6.7(ula)19(t)6.1(ed f)-9.7(r)13.3(o)12.4(m)0.1( a s)-7.8(e)0.2(t o)12.4(f)]TJ T* 0.0041 Tc -0.0091 Tw [(r)-9.4(u)-4.7(les f)9.3(o)12.6(r t)-5.6(h)4.4(e f)-9.5(r)13.5(eq)10.2(uencies o)12.6(f)0.3( t)-5.6(h)4.4(e dif)-9.5(f)9.3(er)13.5(en)19.3(t typ)-8.5(e)0.4(s o)12.6(f)0.3( ma)19.3(tin)8.4(g)0.4(s in a p)-8.5(o)11.6(p)11.5(u)-4.7(la)19.3(tio)12.6(n)0.3(. The)]TJ T* -0.0046 Tc -0.0004 Tw [(sim)19.1(p)7(les)5.1(t)-0.1( cas)-7.9(e)0.1( is w)-6.8(h)4.1(en t)-5.9(h)4.1(er)13.2(e is a mixt)9.9(u)-0.1(r)13.2(e)0.1( o)12.3(f)0( ra)8.9(ndo)12.3(m)0( ma)18.9(tin)8(g)0.1( a)8.9(n)4.1(d s)-7.9(e)4.2(lf-f)9(er)-9.7(tiliza)18.9(tio)12.3(n)]TJ T* 0.0054 Tc 0.0184 Tw [(wi)13(t)-5.2(h)0.7( f)-9.1(r)13.9(eq)10.6(uenc)-15.1(y )]TJ /F3 1 Tf 6.3423 0 TD 0 Tc 0 Tw (S)Tj /F6 1 Tf 0.7233 0 TD 0.0048 Tc 0.019 Tw [(\(t)-5.8(he p)12.3(r)13.3(o)5.4(b)-4.7(a)8.1(b)12.4(ili)12.4(t)-2.9(y t)-5.8(h)3.2(a)19.1(t)0.1( a zyg)8.3(o)11.5(t)6.2(e)0.2( is t)-5.8(h)4.2(e p)12.3(r)13.3(o)-8.6(d)12.4(uc)-6.7(t o)12.4(f)0.1( s)-7.8(e)4.3(lf-f)9.1(e)0.2(r)-9.6(t)-4.8(iliza-)]TJ -7.0656 -1.1818 TD -0.0123 Tc 0.0073 Tw [(t)-17.2(i)-12.3(on)-12.3(,)-12.2( or)-12.3( t)-18.2(h)-8.2(e)-12.2( )]TJ /F3 1 Tf 4.651 0 TD -0.012 Tc 0.0072 Tw [(s)-15(e)4.1(lf)-19.9(ing)-12.1( r)6.9(a)10.1(te)]TJ /F6 1 Tf 4.1747 0 TD -0.001 Tc -0.004 Tw [(\), as in ma)7.9(n)22.2(y)-1.1( s)4.1(p)-9.8(ecies o)11.3(f)-1( her)-6.8(m)2.2(a)17.9(p)6(hr)12.2(o)-9.7(d)-1(i)11.3(t)-5.9(ic o)11.3(r)7.1(ga)7.9(nism)7.1(s, s)4.1(u)-1.1(c)5.1(h)]TJ -8.8256 -1.1818 TD -0.0034 Tc -0.0016 Tw [(as ma)8.5(n)22.8(y)-0.5( f)-16.3(l)-0.5(o)15.8(w)7.7(er)-6.3(in)7.6(g p)6.6(l)-3.4(a)8.5(n)18.6(ts. This is called t)-6.3(h)3.7(e )30.5(mix)7.6(ed ma)18.5(tin)7.6(g)-0.3( mo)-9.1(del)25.6()-0.4( \(B)7.6(r)12.8(o)15.8(wn a)8.5(n)3.7(d)]TJ T* 0.0053 Tc 0.0421 Tw [(Alla)9.6(r)13.8(d)0.7( 1970; Ri)12.9(t)-5.3(l)-2.4(a)9.6(n)4.8(d 1990b\). 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The in)10(b)12.3(r)13.2(eedin)8.1(g co)-8.7(ef)-9.8(f)-9.8(i)0.1(cien)19.1(t)]TJ T* -0.0052 Tc -0.0225 Tw [(in t)-6.2(h)3.8(e next g)7.9(e)-0.2(nera)18.7(tio)12(n)-0.3(, )]TJ /F3 1 Tf 9.0185 0 TD 0 Tc 0 Tw (f)Tj /F7 1 Tf 0.457 0 TD ()Tj /F6 1 Tf 0.2418 0 TD -0.0045 Tc -0.0232 Tw [(, is t)-5.5(h)4.5(er)13.6(ef)9.4(o)12.7(r)13.6(e gi)7.6(v)8.5(e)0.5(n b)16.6(y)0.3( )]TJ /F1 1 Tf 8.4902 0 TD -0.0039 Tc -0.023 Tw [(E)-16.5(q)12.4(ua)16.4(t)6.4(i)-4.7(o)11.2(n)1.2( B1.6.1)]TJ /F6 1 Tf 6.6131 0 TD 0 Tc 0 Tw (:)Tj 0.9468 -2.5911 TD -0.0049 Tc (\(B1.6.1\))Tj -25.7674 -2.6818 TD -0.0047 Tc -0.023 Tw [(The c)6.3(h)3.3(a)9.2(n)8.3(g)8.4(e)0.3( in in)10.2(b)12.5(r)13.4(eedin)8.3(g co)-8.5(ef)-9.6(f)-9.6(i)0.3(cien)19.3(t, )]TJ /F17 1 Tf 14.7663 0 TD 0 Tc 0 Tw ()Tj /F3 1 Tf 0.6047 0 TD (f)Tj /F6 1 Tf 0.2662 0 TD -0.0058 Tc -0.0219 Tw (, is:)Tj 10.1301 -2.7267 TD -0.0049 Tc 0 Tw (\(B1.6.2\))Tj -25.7674 -3.0454 TD -0.0041 Tc -0.0214 Tw [(F)19.9(o)13.1(r small )]TJ /F3 1 Tf 3.88 0 TD 0 Tc 0 Tw (f)Tj /F6 1 Tf 0.2662 0 TD -0.005 Tc (, )Tj /F17 1 Tf 0.4245 0 TD 0 Tc ()Tj /F3 1 Tf 0.6047 0 TD (f)Tj /F7 1 Tf 0.4677 0 TD (>)Tj /F6 1 Tf 0.7453 0 TD -0.0041 Tc -0.0214 Tw [(0, unles)5.9(s)0.8( )]TJ /F3 1 Tf 3.5616 0 TD 0 Tc 0 Tw (S)Tj /F6 1 Tf 0.6645 0 TD -0.005 Tc -0.0205 Tw [(= 0. Als)-8(o)29.1(, unless )]TJ /F3 1 Tf 6.5425 0 TD 0 Tc 0 Tw (S)Tj /F6 1 Tf 0.6645 0 TD -0.0042 Tc -0.0213 Tw [(= 1, a)19.7(t)0.7( la)9.7(r)8.8(g)8.9(e )]TJ /F3 1 Tf 4.7035 0 TD 0 Tc 0 Tw (f)Tj /F6 1 Tf 0.4677 0 TD -0.0037 Tc -0.0218 Tw [(val)13.4(u)1.1(es w)9.3(e)1.3( m)20.3(u)4.3(s)6.3(t)]TJ -22.9927 -1.1818 TD 0.0011 Tc 0 Tw [(ha)14.4(ve )]TJ /F17 1 Tf 2.0863 0 TD 0 Tc ()Tj /F3 1 Tf 0.619 0 TD (f)Tj /F7 1 Tf 0.5116 0 TD (<)Tj /F6 1 Tf 0.7896 0 TD 0.0054 Tc 0.0034 Tw [(0. The in)10.7(b)13(r)13.9(eedin)8.8(g co)-8(ef)-9.1(f)-9.1(i)0.8(cien)19.8(t t)-5.2(h)4.8(er)13.9(ef)9.7(o)13(r)13.9(e a)19.7(p)11.9(p)12.9(r)13.9(oac)6.8(h)4.8(es a)9.7(n)0.7( eq)10.6(uilib-)]TJ -4.0064 -1.1818 TD 0.0014 Tc -0.0065 Tw [(ri)18.6(u)6.2(m)6.3( a)25.3(t)6.3( wh)6.3(i)6.4(c)12.4(h)6.3( )]TJ /F3 1 Tf 5.7639 0 TD 0 Tc 0 Tw (f)Tj /F7 1 Tf 0.4569 0 TD ()Tj /F6 1 Tf 0.4637 0 TD -0.005 Tc (= )Tj /F3 1 Tf 0.7969 0 TD 0 Tc (f)Tj /F6 1 Tf 0.2662 0 TD -0.0053 Tc 0.0002 Tw [(. 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The r)12.6(e)-0.5(s)4.5(u)-5.6(l)11.6(ts f)8.4(o)11.7(r h)18.4(u)-0.7(ma)8.3(n)7.5(s)-0.7( w)7.5(e)-0.5(r)12.6(e)-0.5( o)4.6(b)10.7(t)-6.5(a)8.3(ined in tw)7.5(o wa)17.4(ys; t)-6.5(h)3.5(e f)-10.4(i)-0.5(r)5.5(s)4.5(t was)]TJ T* -0.0018 Tc -0.0032 Tw [(t)5.1(o)-0.8( us)-8.8(e co)11.4(m)18.1(p)-5.9(a)8(r)-6.8(is)-8.8(o)11.4(n)7.1(s o)11.4(f)-1( no)11.4(nco)-9.6(din)7.1(g D)8.1(N)37.1(A s)-8.8(e)-5.8(q)8.9(u)-1.1(ences b)-9.7(e)-0.9(tw)7.2(een h)18(u)-1.1(ma)8(n)7.1(s)-1( a)8(n)3.2(d c)5.2(h)-1(im-)]TJ T* -0.0048 Tc -0.0303 Tw [(pa)9.1(nzees, usin)8.2(g t)-5.8(h)4.2(e p)12.3(r)-5.7(inci)12.4(p)7.2(l)0.1(es des)-7.8(cr)-5.7(ib)-8.6(ed in )]TJ /F1 1 Tf 16.4017 0 TD -0.0051 Tc -0.0289 Tw [(S)-11.9(e)-12.8(c)-5.8(t)5.2(i)-5.9(o)10(n 6.1.ii)]TJ /F6 1 Tf 5.5172 0 TD -0.03 Tw [(\(N)25.9(ac)5.9(hma)8.8(n)-0.2( a)8.8(n)4(d Cr)13(o)16(w)7.9(ell)]TJ -21.919 -1.1818 TD 0.0044 Tc -0.009 Tw [(2000\). The s)-8.2(e)-5.1(co)12(nd us)-8.2(ed da)18.7(t)-6.2(a)-0.4( o)12(n)-0.3( t)-6.2(h)3.8(e ra)18.7(t)5.8(e)-0.2(s o)12(f)-0.3( o)-9(c)-0.3(c)-7.1(u)-0.4(r)-6.1(r)12.9(ence in t)-6.2(h)3.8(e h)18.7(u)-0.4(ma)8.7(n p)-9.1(o)11.1(p)10.9(u)-5.3(la-)]TJ T* 0.0047 Tc 0.3794 Tw [(tio)12.3(n)8.1(s o)12.3(f)0( dis)-7.9(e)-5.8(as)-7.9(e-ca)19(usin)8.1(g ne)-7.7(w m)19.1(u)12.1(t)-5.9(a)19(tio)12.3(n)8.1(s wi)12.3(t)-5.9(h)0( kno)16.2(w)-2.8(n c)6.1(h)3.1(a)9(n)8.1(g)8.2(e)0.1(s in D)9.1(N)38.1(A)]TJ T* 0.0044 Tc 0.0611 Tw [(s)-8.2(e)-5.1(q)9.6(u)-0.4(ences; m)18.8(u)11.8(t)-6.2(a)18.7(tio)12(n)7.8(s in 20 g)7.9(e)-0.2(nes w)7.8(e)-0.2(r)12.9(e)-0.2( s)4.8(t)9.7(udied \(K)23.9(o)12(n)3.9(drasho)15.9(v 2003\). The tw)7.8(o)]TJ T* 0.0046 Tc 0.0758 Tw [(met)-6(h)4(o)-8.8(d)3.1(s ga)17.9(v)8(e)0( v)8(e)0(r)-28.9(y)-0.2( simila)8.9(r r)13.1(e)0(s)5(u)-5.1(l)12.1(ts. The da)18.9(t)-6(a)-0.2( f)8.9(o)12.2(r o)11.3(t)-6(her o)12.2(r)8(ga)8.9(nism)8(s co)12.2(me f)-9.9(r)13.1(o)12.2(m)]TJ T* -0.0007 Tc -0.0051 Tw [(exp)-9.2(e)-0.3(r)-6.2(i)-0.3(men)18.7(t)-0.4(s in w)-7.2(h)-0.4(ic)5.7(h t)-6.3(h)3.7(e ra)18.6(t)5.7(e)-0.3(s o)16.7(f)4.4( occurr)]TJ 16.0558 0 TD -0.0149 Tc 0.0051 Tw [(e)-9.7(n)-5.6(c)-9.8(e)-9.7( of)-9.8( m)9.3(u)2.3(t)-15.7(a)9.2(t)-14.7(i)-9.7(ons)-9.9( c)-3.7(h)-6.7(ang)-14.6(i)-9.7(ng)-9.7( s)-17.7(e)-14.6(qu)-9.9(e)-9.7(n)-5.6(c)-9.8(e)-9.7(s)]TJ -16.0558 -1.1818 TD -0.0152 Tc -0.0227 Tw [(we)-5.4(r)7.7(e)-5.4( me)-11.3(asu)-5.6(r)7.7(e)-10.3(d)0.7(.)-5.4( )]TJ /F1 1 Tf 6.2483 0 TD -0.0096 Tc 0 Tw [(F)8.5(i)0.5(gur)8.6(e)-179.3(1.13)]TJ /F6 1 Tf 4.7461 0 TD -0.0116 Tc -0.0263 Tw [(sho)14.3(ws ho)14.3(w t)-7.8(h)2.2(e )]TJ /F3 1 Tf 5.8734 0 TD -0.0108 Tc -0.0271 Tw [(D)26.1(.)-1.1( m)5.9(e)14.9(la)14.9(n)5.8(ogas)8.8(t)8.9(er)]TJ /F6 1 Tf 6.3388 0 TD -0.0076 Tc -0.0303 Tw [(n)21.2(u)2(c)8.2(l)2.1(eo)13.5(tide m)21.2(u)14.2(t)-3.8(a)21.1(tio)14.4(n)]TJ -23.2066 -1.1818 TD -0.0027 Tc -0.0071 Tw [(ra)18(t)5.1(e)-0.9( was estima)18(t)5.1(e)-5.8(d)5.2(.)-0.9( The y)7(e)-6.8(ast a)8(n)3.2(d )]TJ /F3 1 Tf 13.3943 0 TD -0.0018 Tc -0.0077 Tw [(C. e)16(l)4.2(e)8.9(g)-0.1(a)15.9(n)-0.2(s)]TJ /F6 1 Tf 4.0739 0 TD -0.01 Tc 0.0002 Tw [(e)-8.2(s)-3.2(t)-13.2(i)-8.2(ma)10.7(te)-8.2(s)-8.3( we)-8.2(r)4.9(e)-8.2( b)-13.1(a)-5.2(s)-16.2(e)-13.1(d)-8.2( on)-8.3( d)-11.2(a)10.7(t)-14.2(a)-8.4( f)-18.1(r)4.9(om)]TJ -17.4683 -1.1818 TD 0 Tc 0.0682 Tw [(s)-7.8(e)-4.7(q)10(u)0(ences o)12.4(f)0.1( t)-5.8(h)4.2(e g)8.3(e)0.2(no)12.4(mes o)12.4(f)0.1( indi)7.3(vid)12.4(u)-2.9(als allo)16.3(w)8.2(e)-4.7(d t)6.2(o)0.2( acc)-6.7(u)0(m)19.2(u)-4.9(la)19.1(t)6.2(e)0.2( m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)8.2(s in)]TJ T* -0.0093 Tc -0.0232 Tw [(simila)9.4(r )194.5(exp)-8.4(e)0.5(r)-5.4(i)0.5(men)19.5(ts.)]TJ 1.0909 -1.1818 TD -0.0053 Tc -0.0292 Tw [(M)32.8(u)11.7(t)-6.3(a)18.6(tio)11.9(n)-0.4( ra)18.6(t)5.7(e)-0.3(s in most D)8.7(N)37.7(A)43.8(-)-0.5(bas)-8.3(e)-5.2(d g)7.8(e)-0.3(no)11.9(mes a)8.6(r)12.8(e lo)15.8(w b)-9.1(e)-5.2(ca)18.6(us)-8.3(e t)-6.3(h)3.7(er)12.8(e a)8.6(r)12.8(e ela)7.6(b)-9.1(o-)]TJ -1.0909 -1.1818 TD 0.0052 Tc 0.2035 Tw [(ra)19.5(t)6.6(e)0.6( mo)7.7(lec)-6.3(u)-4.5(la)9.5(r mec)6.6(h)3.6(a)9.5(n)0.5(ism)8.6(s)0.5( f)9.5(o)12.8(r co)12.8(r)-5.3(r)13.7(ec)-6.3(tin)8.6(g)0.6( er)-5.3(r)13.7(o)12.8(r)6.6(s)0.5( in D)9.6(N)38.6(A r)13.7(e)0.6(p)7.5(l)0.5(ica)19.5(t)-4.4(io)12.8(n a)9.5(n)4.7(d)]TJ T* 0.0011 Tc -0.0061 Tw [(r)13.8(e)0.7(pa)9.5(ir)-5.2(in)8.7(g D)9.6(N)38.6(A da)9.5(mag)8.8(e)6.8(, a)9.5(n)4.8(d m)19.7(u)12.7(t)-5.3(a)19.6(tio)12.9(n)0.6( ra)19.6(t)6.6(e)0.7(s a)9.5(r)13.8(e gr)13.8(e)-5.2(a)19.6(t)-5.3(l)7.6(y incr)13.8(e)-5.2(a)3.7(s)-7.3(e)-4.2(d b)16.8(y)0.5( m)19.7(u)12.7(t)-5.3(a)19.6(tio)12.9(n)8.7(s)]TJ T* 0.0048 Tc 0.1228 Tw [(in t)-5.8(h)4.2(e g)8.3(e)0.2(nes co)12.4(n)19.2(t)-4.8(r)13.3(o)7.3(llin)8.2(g t)-5.8(h)4.2(em \(Drak)9.2(e)0.2( et al)6.2(. 1998\). G)-7.7(e)0.2(no)12.4(mes t)-5.8(h)3.2(a)19.1(t)0.1( lac)6.2(k)0.1( s)5.2(u)0(c)6.2(h)]TJ T* -0.0024 Tc -0.0026 Tw [(mec)6.1(h)3.1(a)8.9(n)0(ism)8.1(s)-0.1(, s)5(u)-0.1(c)6.1(h)-0.1( as RN)38(A vir)-9.8(u)3(s)-7.9(e)0.1(s \(Drak)9(e)0.1( et al)6(. 1998\) a)8.9(n)4.1(d a)8.9(nimal mi)12.2(t)6(o)-8.7(c)6.1(h)4.1(o)12.3(n)4.1(dr-)]TJ T* -0.0042 Tc -0.0008 Tw [(ial D)9.3(N)38.3(A \(H)24.5(aa)5.3(g-L)-5.5(i)-2.6(a)19.2(u)12.4(t)-5.6(a)9.2(r)13.5(d)0.3( et al)6.3(. 2008\), ha)18.3(v)8.3(e)0.4( m)19.4(u)0.2(c)6.4(h)0.2( hig)-6.5(h)4.4(er m)19.4(u)12.4(t)-5.6(a)19.2(tio)12.6(n)0.3( ra)19.2(t)6.3(e)0.4(s. I)16.5(n)0.3( m)19.4(u)-4.7(l-)]TJ T* -0.0048 Tc -0.0108 Tw [(ticell)12.3(ula)9.1(r)0.1( o)12.4(r)8.2(ga)9.1(nism)8.2(s wi)12.4(t)-5.8(h)0.1( a g)8.3(e)0.2(r)-5.7(m)0.1( line)6.3(, m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)8.2(s ca)9.1(n a)9.1(r)-5.7(is)-7.8(e in g)8.3(e)0.2(r)-5.7(m)0.1(-line cell line-)]TJ T* 0.0014 Tc -0.0064 Tw [(ag)7.8(es b)-9.1(e)-0.3(f)8.7(o)12(r)12.9(e)-0.3( meiosis. A c)5.8(l)11.8(ust)5.7(er o)12(f)-0.4( iden)18.7(tical m)18.7(u)11.7(t)-6.3(a)18.6(tio)12(n)7.7(s ma)17.6(y t)-6.3(h)3.7(er)12.9(ef)8.7(o)12(r)12.9(e a)18.6(p)10.8(p)-9.2(e)-6.1(a)8.6(r)-0.3( in a)]TJ T* 0.0048 Tc -0.0066 Tw [(b)12.4(r)13.3(o)-8.6(o)-8.6(d)0.2( o)12.4(f)0.1( o)12.4(f)-9.7(fs)5.2(p)12.3(r)-5.7(in)8.2(g, ra)19.1(t)-5.8(h)4.2(er t)-5.8(h)3.2(a)9.1(n)0.1( j)10.1(u)3.2(s)5.2(t)0.1( a sin)8.2(g)-6.6(le m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)0.1( \(W)97.2(o)-8.6(o)-8.6(d)0.2(r)-9.6(u)0(f)-9.7(f)0.1( a)9.1(n)4.3(d Tho)12.4(m)19.2(p-)]TJ T* 0.0371 Tw [(s)-7.8(o)12.4(n 1992, 2005\). The a)8.1(b)-8.6(o)16.3(v)8.2(e m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)0.1( ra)19.1(t)6.2(e)0.2(s f)9.1(o)12.4(r m)19.2(u)-4.9(l)12.3(t)-4.8(icell)12.3(u)-4.9(la)9.1(r o)12.4(r)8.2(ga)9.1(nism)8.2(s ef)-9.7(f)9.1(e)-4.7(c-)]TJ T* -0.0021 Tc -0.0029 Tw [(ti)6.7(v)7.6(e)3.8(l)6.6(y)-0.5( co)10.9(un)18.6(t e)-6.2(a)-0.5(c)5.7(h)-0.5( m)18.6(u)11.7(t)-6.3(a)18.5(tio)11.9(n)-0.4( in a c)5.7(l)11.7(ust)5.6(er w)-7.2(h)3.7(en estima)18.5(tin)7.6(g)-0.3( t)-6.3(h)3.7(e m)18.6(u)11.6(t)-6.3(a)18.5(tio)11.9(n)-0.4( ra)18.5(t)5.6(e)5.8(, as is)]TJ T* -0.0051 Tc -0.0235 Tw [(a)18.8(p)11(p)12(r)13(o)11.2(p)12(r)-6(i)-3.1(a)18.8(t)5.9(e f)8.8(o)12.1(r under)6(st)-6.1(a)8.8(n)4(din)7.9(g t)-6.1(h)3.9(e co)12.1(n)18.9(t)-5.1(r)-6(i)4(b)11.1(u)11.9(tio)12.1(n)-0.2( o)12.1(f)-0.2( m)18.9(u)11.9(t)-6.1(a)18.8(tio)12.1(n)7.9(s t)5.9(o)-0.1( t)-6.1(h)3.9(e ra)18.8(t)5.9(e)-0.1( o)12.1(f)-0.2( D)8.9(N)37.9(A)]TJ T* -0.0055 Tc -0.0222 Tw [(s)-8.5(e)-5.4(q)9.3(u)-0.7(ence e)-8.3(v)7.5(o)6.6(l)11.6(u)11.5(t)-5.5(io)11.7(n \()]TJ /F1 1 Tf 8.0816 0 TD 0 Tw [(S)-12.3(e)-13.2(c)-6.2(t)4.8(i)-6.3(o)9.6(n)-199.7(6)-0.5(.2.ii.b)]TJ /F6 1 Tf 6.1163 0 TD -0.0048 Tc (\).)Tj /F1 1 Tf -7.4221 -2.3636 TD 0.0496 Tc [(1.3.iii.c)-8.1(.)]TJ /F3 1 Tf 4.0559 0 TD -0.0099 Tc 0.0099 Tw [(M)18.2(u)4.3(ta)12.3(ti)-5.7(on)-9.9( a)6.2(n)-2.8(d)-9.7( e)-13.7(v)-5.5(oluti)-5.7(o)0.1(na)6.2(r)-29.6(y)-9.8( cha)6.2(n)3.3(g)-9.8(e)]TJ /F6 1 Tf -10.8317 -1.1818 TD -0.0047 Tc -0.0226 Tw [(Al)12.4(t)-5.7(h)4.3(o)11.6(u)0.1(g)-6.5(h)0.2( m)19.3(u)12.3(t)-5.7(a)19.2(tio)12.5(n)8.3(s a)9.2(r)13.4(e im)19.3(p)-8.6(o)12.5(r)-9.5(t)-5.7(a)9.2(n)19.3(t as t)-5.7(h)4.3(e s)-7.7(o)11.6(ur)13.4(ce o)12.5(f)0.2( va)9.2(r)-5.6(i)-2.7(a)19.2(t)-4.7(io)12.5(n f)9.2(o)12.5(r e)-7.5(v)8.3(o)7.4(l)12.4(u)12.3(t)-4.7(io)12.5(n, t)-5.7(h)4.3(eir)]TJ T* -0.0054 Tc [(lo)15.7(w ra)18.5(t)5.6(e)-0.4( o)11.8(f)-0.5( o)-9.2(c)-0.5(c)-7.3(u)-0.6(r)-6.3(r)12.7(ence me)-6.3(a)8.5(n)7.6(s t)-6.4(h)2.6(a)18.5(t)-0.5( m)18.6(u)11.6(t)-6.4(a)18.5(tio)11.8(n)-0.5( is a)8.5(n)-0.5( inef)-10.3(f)8.5(e)-5.3(c)-7.3(t)-5.4(i)6.7(v)7.6(e f)8.5(o)11.8(r)12.7(c)-0.5(e f)8.5(o)11.8(r e)-8.2(v)7.6(o)6.7(l)11.7(u)11.6(t)-5.4(io)11.8(n-)]TJ T* -0.0022 Tc -0.0028 Tw [(a)7.8(r)-30(y c)5(h)1.9(a)7.8(n)6.9(g)7(e)-1.1( a)17.8(t)-1.2( a)7.8(n)-1.2( indi)6(vid)11.1(u)-4.2(al si)11.1(t)4.9(e)-1.1( in t)-7.1(h)2.9(e g)7(e)-1.1(no)11.1(me)5(. 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596.75 l 284.082 596.07 283.245 595.387 282.406 594.705 c 282.803 595.601 283.2 596.496 283.597 597.393 c 284.226 600.21 l 284.295 600.243 l 285.406 598.539 l f 309.867 615.957 m 300.96 598.568 l S 301.134 599.009 m 303.483 599.477 l 303.507 599.413 l 301.233 597.182 l 300.641 596.357 300.048 595.531 299.453 594.705 c 299.553 595.65 299.65 596.596 299.747 597.54 c 299.455 600.393 l 299.512 600.438 l 301.134 599.009 l f 332.285 615.746 m 329.121 598.729 l S 329.176 599.188 m 331.352 600.026 l 331.392 599.967 l 329.746 597.416 l 329.384 596.513 329.018 595.609 328.653 594.705 c 328.503 595.647 328.351 596.587 328.2 597.528 c 327.172 600.272 l 327.215 600.327 l 329.176 599.188 l f 320.555 615.912 m 315.658 598.699 l S 315.747 599.155 m 317.988 599.884 l 318.024 599.823 l 316.179 597.357 l 315.744 596.475 315.31 595.59 314.873 594.705 c 314.798 595.652 314.721 596.599 314.645 597.545 c 313.834 600.334 l 313.882 600.385 l 315.747 599.155 l f 342.262 615.641 m 342.262 598.746 l S 342.262 599.207 m 344.334 600.199 l 344.382 600.144 l 343.04 597.484 l 342.781 596.558 342.523 595.631 342.262 594.705 c 342.004 595.631 341.744 596.558 341.487 597.484 c 340.145 600.144 l 340.181 600.199 l 342.262 599.207 l f [1 1 1 1 1 1 ]0 d 251.269 566.461 m 251.269 520.149 l S 251.269 520.61 m 253.342 521.603 l 253.389 521.547 l 252.048 518.888 l 251.787 517.961 251.53 517.035 251.269 516.108 c 251.012 517.035 250.751 517.961 250.494 518.888 c 249.152 521.547 l 249.188 521.603 l 251.269 520.61 l f 266.521 566.461 m 266.521 520.149 l S 266.521 520.61 m 268.594 521.603 l 268.64 521.547 l 267.298 518.888 l 267.039 517.961 266.78 517.035 266.521 516.108 c 266.262 517.035 266.003 517.961 265.744 518.888 c 264.402 521.547 l 264.438 521.603 l 266.521 520.61 l f 281.773 566.461 m 281.773 520.149 l S 281.773 520.61 m 283.846 521.603 l 283.892 521.547 l 282.55 518.888 l 282.291 517.961 282.032 517.035 281.773 516.108 c 281.514 517.035 281.255 517.961 280.995 518.888 c 279.654 521.547 l 279.69 521.603 l 281.773 520.61 l f 298.559 566.461 m 298.559 520.149 l S 298.559 520.61 m 300.632 521.603 l 300.677 521.547 l 299.335 518.888 l 299.078 517.961 298.817 517.035 298.559 516.108 c 298.299 517.035 298.041 517.961 297.781 518.888 c 296.439 521.547 l 296.475 521.603 l 298.559 520.61 l f 312.275 566.461 m 312.275 520.149 l S 312.275 520.61 m 314.347 521.603 l 314.394 521.547 l 313.052 518.888 l 312.793 517.961 312.534 517.035 312.275 516.108 c 312.016 517.035 311.757 517.961 311.498 518.888 c 310.156 521.547 l 310.192 521.603 l 312.275 520.61 l f 327.527 566.461 m 327.527 520.149 l S 327.527 520.61 m 329.599 521.603 l 329.646 521.547 l 328.304 518.888 l 328.045 517.961 327.785 517.035 327.527 516.108 c 327.268 517.035 327.009 517.961 326.749 518.888 c 325.408 521.547 l 325.444 521.603 l 327.527 520.61 l f 342.778 566.461 m 342.778 520.149 l S 342.778 520.61 m 344.85 521.603 l 344.898 521.547 l 343.556 518.888 l 343.295 517.961 343.037 517.035 342.778 516.108 c 342.52 517.035 342.259 517.961 342.001 518.888 c 340.659 521.547 l 340.696 521.603 l 342.778 520.61 l f 356.494 566.461 m 356.494 520.149 l S 356.494 520.61 m 358.567 521.603 l 358.613 521.547 l 357.272 518.888 l 357.012 517.961 356.753 517.035 356.494 516.108 c 356.235 517.035 355.976 517.961 355.717 518.888 c 354.375 521.547 l 354.411 521.603 l 356.494 520.61 l f 370.211 566.461 m 370.211 520.149 l S 370.211 520.61 m 372.283 521.603 l 372.33 521.547 l 370.989 518.888 l 370.729 517.961 370.47 517.035 370.211 516.108 c 369.952 517.035 369.693 517.961 369.434 518.888 c 368.092 521.547 l 368.128 521.603 l 370.211 520.61 l f 385.461 566.461 m 385.461 520.149 l S 385.461 520.61 m 387.533 521.603 l 387.582 521.547 l 386.241 518.888 l 385.98 517.961 385.722 517.035 385.461 516.108 c 385.203 517.035 384.944 517.961 384.686 518.888 c 383.344 521.547 l 383.38 521.603 l 385.461 520.61 l f 402.248 566.461 m 402.248 520.149 l S 402.248 520.61 m 404.321 521.603 l 404.367 521.547 l 403.026 518.888 l 402.766 517.961 402.507 517.035 402.248 516.108 c 401.99 517.035 401.73 517.961 401.471 518.888 c 400.129 521.547 l 400.165 521.603 l 402.248 520.61 l f 417.5 566.461 m 417.5 520.149 l S 417.5 520.61 m 419.573 521.603 l 419.619 521.547 l 418.278 518.888 l 418.018 517.961 417.759 517.035 417.5 516.108 c 417.241 517.035 416.982 517.961 416.723 518.888 c 415.381 521.547 l 415.417 521.603 l 417.5 520.61 l f 434.285 566.461 m 434.285 520.149 l S 434.285 520.61 m 436.358 521.603 l 436.406 521.547 l 435.064 518.888 l 434.803 517.961 434.546 517.035 434.285 516.108 c 434.028 517.035 433.767 517.961 433.51 518.888 c 432.168 521.547 l 432.203 521.603 l 434.285 520.61 l f []0 d 251.269 502.314 m 251.269 485.163 l S 251.269 485.624 m 253.342 486.616 l 253.389 486.561 l 252.048 483.901 l 251.787 482.975 251.53 482.048 251.269 481.122 c 251.012 482.048 250.751 482.975 250.494 483.901 c 249.152 486.561 l 249.188 486.616 l 251.269 485.624 l f 266.521 502.314 m 266.521 485.163 l S 266.521 485.624 m 268.594 486.616 l 268.64 486.561 l 267.298 483.901 l 267.039 482.975 266.78 482.048 266.521 481.122 c 266.262 482.048 266.003 482.975 265.744 483.901 c 264.402 486.561 l 264.438 486.616 l 266.521 485.624 l f 281.773 502.314 m 281.773 485.163 l S 281.773 485.624 m 283.846 486.616 l 283.892 486.561 l 282.55 483.901 l 282.291 482.975 282.032 482.048 281.773 481.122 c 281.514 482.048 281.255 482.975 280.995 483.901 c 279.654 486.561 l 279.69 486.616 l 281.773 485.624 l f 298.559 502.314 m 298.559 485.163 l S 298.559 485.624 m 300.632 486.616 l 300.677 486.561 l 299.335 483.901 l 299.078 482.975 298.817 482.048 298.559 481.122 c 298.299 482.048 298.041 482.975 297.781 483.901 c 296.439 486.561 l 296.475 486.616 l 298.559 485.624 l f 312.275 502.314 m 312.275 485.163 l S 312.275 485.624 m 314.347 486.616 l 314.394 486.561 l 313.052 483.901 l 312.793 482.975 312.534 482.048 312.275 481.122 c 312.016 482.048 311.757 482.975 311.498 483.901 c 310.156 486.561 l 310.192 486.616 l 312.275 485.624 l f 327.527 502.314 m 327.527 485.163 l S 327.527 485.624 m 329.599 486.616 l 329.646 486.561 l 328.304 483.901 l 328.045 482.975 327.785 482.048 327.527 481.122 c 327.268 482.048 327.009 482.975 326.749 483.901 c 325.408 486.561 l 325.444 486.616 l 327.527 485.624 l f 342.778 502.314 m 342.778 485.163 l S 342.778 485.624 m 344.85 486.616 l 344.898 486.561 l 343.556 483.901 l 343.295 482.975 343.037 482.048 342.778 481.122 c 342.52 482.048 342.259 482.975 342.001 483.901 c 340.659 486.561 l 340.696 486.616 l 342.778 485.624 l f 356.494 502.314 m 356.494 485.163 l S 356.494 485.624 m 358.567 486.616 l 358.613 486.561 l 357.272 483.901 l 357.012 482.975 356.753 482.048 356.494 481.122 c 356.235 482.048 355.976 482.975 355.717 483.901 c 354.375 486.561 l 354.411 486.616 l 356.494 485.624 l f 370.211 502.314 m 370.211 485.163 l S 370.211 485.624 m 372.283 486.616 l 372.331 486.561 l 370.99 483.901 l 370.729 482.975 370.472 482.048 370.211 481.122 c 369.953 482.048 369.693 482.975 369.436 483.901 c 368.094 486.561 l 368.129 486.616 l 370.211 485.624 l f 385.463 502.314 m 385.463 485.163 l S 385.463 485.624 m 387.535 486.616 l 387.582 486.561 l 386.241 483.901 l 385.981 482.975 385.722 482.048 385.463 481.122 c 385.203 482.048 384.945 482.975 384.686 483.901 c 383.344 486.561 l 383.38 486.616 l 385.463 485.624 l f 402.248 502.314 m 402.248 485.163 l S 402.248 485.624 m 404.321 486.616 l 404.367 486.561 l 403.026 483.901 l 402.766 482.975 402.507 482.048 402.248 481.122 c 401.99 482.048 401.73 482.975 401.471 483.901 c 400.129 486.561 l 400.165 486.616 l 402.248 485.624 l f 417.5 502.314 m 417.5 485.163 l S 417.5 485.624 m 419.573 486.616 l 419.619 486.561 l 418.278 483.901 l 418.018 482.975 417.759 482.048 417.5 481.122 c 417.241 482.048 416.982 482.975 416.723 483.901 c 415.381 486.561 l 415.417 486.616 l 417.5 485.624 l f 434.285 502.314 m 434.285 485.163 l S 434.285 485.624 m 436.358 486.616 l 436.406 486.561 l 435.064 483.901 l 434.803 482.975 434.546 482.048 434.285 481.122 c 434.028 482.048 433.767 482.975 433.51 483.901 c 432.168 486.561 l 432.203 486.616 l 434.285 485.624 l f 393.895 615.545 m 413.039 598.023 l S 412.706 598.401 m 410.286 598.285 l 410.286 598.218 l 413.318 596.638 l 414.201 595.994 415.084 595.349 415.971 594.705 c 415.51 595.582 415.052 596.458 414.593 597.336 c 413.767 600.122 l 413.698 600.151 l 412.706 598.401 l f 403.871 615.832 m 427.765 597.801 l S 427.388 598.154 m 424.992 597.867 l 425.001 597.8 l 428.2 596.44 l 429.152 595.863 430.108 595.284 431.063 594.705 c 430.505 595.547 429.946 596.387 429.389 597.227 c 428.247 599.944 l 428.172 599.969 l 427.388 598.154 l f 382.679 615.725 m 399.427 598.146 l S 399.118 598.539 m 396.696 598.527 l 396.693 598.46 l 399.607 596.75 l 400.446 596.07 401.281 595.387 402.119 594.705 c 401.721 595.601 401.325 596.496 400.93 597.393 c 400.301 600.21 l 400.233 600.243 l 399.118 598.539 l f 374.658 615.957 m 383.566 598.568 l S 383.392 599.009 m 381.041 599.477 l 381.017 599.413 l 383.293 597.182 l 383.883 596.357 384.476 595.531 385.073 594.705 c 384.973 595.65 384.874 596.596 384.779 597.54 c 385.069 600.393 l 385.012 600.438 l 383.392 599.009 l f 352.24 615.746 m 355.404 598.729 l S 355.35 599.188 m 353.174 600.026 l 353.134 599.967 l 354.78 597.416 l 355.142 596.513 355.507 595.609 355.872 594.705 c 356.023 595.647 356.175 596.587 356.325 597.528 c 357.354 600.272 l 357.31 600.327 l 355.35 599.188 l f 363.97 615.912 m 368.867 598.699 l S 368.777 599.155 m 366.537 599.884 l 366.502 599.823 l 368.345 597.357 l 368.78 596.475 369.215 595.59 369.653 594.705 c 369.728 595.652 369.804 596.599 369.88 597.545 c 370.692 600.334 l 370.642 600.385 l 368.777 599.155 l f /GS4 gs BT /F11 1 Tf 10 0 0 10 248.7493 569.1689 Tm /Cs8 cs 1 scn 1.0795 Tc 0 Tw [(12)77.6(3)-113.6(4)116.7(5)154.1(6)192.6(78)309(9)497.9(1)1079.5(0)304.2(1)1079.5(1)456.7(1)1079.5(2)457.3(1)1079.5(3)]TJ 0 -6.4403 TD 1.0786 Tc (12)Tj 3.0666 -0.0002 TD 1.1931 Tc [(34)230.3(5)267.7(6)306.2(7)112.7(8)422.6(9)611.5(1)1193.1(0)417.8(1)1193.1(1)570.3(1)1193.1(2)570.9(1)1193.1(3)]TJ /F6 1 Tf 2.1618 11.603 TD -0.0005 Tc 0.0005 Tw [(I)15.5(n)-0.5(i)11.5(t)-5.5(ial is)-8.5(og)7.5(enic st)5.5(o)-9.4(c)5.5(k)]TJ 1.108 -15.4121 TD 0.0006 Tc -0.0006 Tw [(D)9.6(N)38.6(A extrac)-6.4(t)6.6(e)-4.4(d)]TJ -4.4719 11.5776 TD 0.0002 Tc -0.0002 Tw [(M)17.2(a)9.2(n)23.2(y)0.2( s)-7.8(e)0.3(pa)9.2(ra)19.2(t)6.2(e)0.2( sin)8.1(g)-6.7(le-pa)9.2(i)0.1(r ma)19.3(t)6.2(e)-4.8(d lines)]TJ -9.3405 -2.6821 TD 0.0001 Tc -0.0001 Tw [(~200 g)8.1(e)0.1(nera)19.1(tio)12.1(n)8.1(s)]TJ -0.556 -1.2 TD 0.003 Tc -0.003 Tw [(t)9(o)3( allo)19(w)3( m)22(u)15(ta)22(tio)15(n)11(s)]TJ 4.5209 -1.2 TD -0.006 Tc 0.006 Tw [(to)-6( ar)-12(is)-14(e)]TJ ET EMC q 0.000031 804 588 -804 re 294 402.015 m W n 0 804.015 588 -804 re W n /GS2 gs BT /F8 1 Tf 9 0 0 9 132 446.1386 Tm 0.017 g 0.151 Tc 0 Tw (\015 )Tj /F6 1 Tf 4.1692 0 TD -0.0048 Tc -0.0002 Tw [(1.13 )-253.2(M)26.3(e)0.2(t)-5.8(h)4.2(o)-8.6(d)0.2( f)9.1(o)12.4(r usin)8.2(g m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)0.1( acc)-6.7(u)0(m)19.2(u)-4.9(la)19.1(tio)12.4(n)0.1( lines t)6.2(o)0.2( estima)19.1(t)6.2(e)0.2( t)-5.8(h)4.2(e m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)0.1( ra)19.1(t)6.2(e)0.2( in)]TJ /F3 1 Tf -4.1692 -1.2222 TD -0.0091 Tc 0.0043 Tw [(D)-8(r)14.7(os)-7.2(op)5.8(h)12.8(i)0.8(la me)11.9(la)11.8(nogas)5.8(t)5.8(e)-4.2(r)]TJ /F6 1 Tf 9.8133 0 TD -0.0048 Tc -0.0002 Tw [(\(H)24.3(aa)5.2(g-L)-5.7(i)-2.8(a)19.1(u)12.2(t)-5.8(a)9.1(r)13.3(d)0.2( et al)6.2(. 2007\). Af)-5.8(t)6.2(e)0.2(r ma)9.1(n)23.3(y)0( g)8.3(e)0.2(nera)19.1(tio)12.4(n)8.2(s o)12.4(f)0.1( m)19.2(u)12.2(t)-5.8(a)19.1(tio)12.4(n)]TJ -9.8133 -1.2222 TD -0.0045 Tc -0.0005 Tw [(acc)-6.4(u)0.3(m)19.5(u)-4.6(la)19.4(tio)12.7(n)0.4(, m)19.5(u)12.5(t)-5.5(a)19.4(tio)12.7(n)8.5(s in a gi)7.6(v)8.5(e)0.5(n s)-7.5(e)-4.4(q)10.3(u)0.3(ence ca)9.4(n b)-8.3(e)0.5( det)6.5(ec)-6.4(t)6.5(e)-4.4(d b)16.6(y)0.3( s)-7.5(e)-4.4(q)10.3(u)0.3(encin)8.5(g)0.5( pa)9.4(r)-9.3(ts o)12.7(f)0.4( t)-5.5(h)4.5(e g)8.6(e)0.5(no)12.7(me)]TJ T* -0.0052 Tc 0.0002 Tw [(in f)-16.2(l)-0.3(ies f)-10.1(r)12.9(o)12(m)-0.3( a)-5.3(l)-5.2(l o)12(f)-0.3( t)-6.2(h)3.8(e lines, o)12(r)-0.3( b)15.9(y)-0.4( met)-6.2(h)3.8(o)-9(d)2.9(s t)-6.2(h)2.8(a)18.7(t)-0.3( det)5.8(ec)-7.1(t t)-6.2(h)2.8(a)18.7(t)-0.3( t)-6.2(h)3.8(e s)-8.2(e)-5.1(q)9.6(u)-0.4(ence o)12(f)-0.3( a g)7.9(e)-0.2(no)12(mic r)12.9(e)-0.2(gio)12(n)-0.3( has)]TJ T* -0.0046 Tc -0.0004 Tw [(c)6.4(h)3.4(a)9.3(n)8.4(g)8.5(e)-4.5(d f)-9.5(r)13.5(o)12.6(m)0.3( 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[(S)-12.4(e)-13.2(c)-6.2(t)4.8(i)-6.3(o)9.6(n 1.2.i.b)]TJ /F6 1 Tf 5.8605 0 TD -0.004 Tc 0.0217 Tw [(, ca)-4.1(lc)-5.9(u)-4.1(l)-2.1(a)19.9(t)7(e)]TJ /F1 1 Tf -18.7742 -1.5 TD -0.0083 Tc 0 Tw (i.)Tj /F6 1 Tf 0.8407 0 TD -0.0171 Tc 0.0348 Tw [(T)-12.3(h)-8.1(e)-12.1( prop)-21(or)-21.9(t)-17.1(i)-12.1(on)-12.2( of)-12.2( p)-21(o)-5(l)-5.2(y)-15.2(m)-8(o)0.1(r)-21.9(p)-5.1(h)-12.2(i)-12.1(c)-12.2( l)-12.2(o)-20.9(c)-12.1(i)-6(.)]TJ /F1 1 Tf -1.1306 -1.2 TD -0.0067 Tc 0 Tw (ii.)Tj /F6 1 Tf 1.1306 0 TD -0.0058 Tc 0.0235 Tw [(The me)-6.7(a)8.1(n)-0.9( g)7.3(e)-0.8(ne di)6.3(v)7.2(e)-0.8(r)5.3(s)-0.9(i)11.4(t)-3.9(y \(het)5.2(er)12.3(o)5.3(z)-0.9(yg)7.3(osi)11.4(t)-3.9(y\).)]TJ /F1 1 Tf -3 -1.8 TD -0.0051 Tc 0 Tw (1.2)Tj /F6 1 Tf 1.8 0 TD -0.0049 Tc -0.0266 Tw [(S)6.1(h)4.1(o)16.2(w)0.1( ho)16.3(w t)-5.9(h)4.1(e H)24.2(a)9(r)13.2(d)7.2(yW)97.1(ein)10(b)-8.7(e)0.1(r)8.1(g)0.1( f)-9.8(r)13.2(eq)9.9(uencies \(s)-7.9(ee )]TJ /F1 1 Tf 19.1898 0 TD -0.0055 Tc -0.025 Tw 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