Uncertainty in Genetic Mapping and Gene Interaction for Diabetes in Rats

Full text

(1)

(2)

(3) !"#$&%'"(#"(()*+,-./$01* &-2"(013401 0 56 " ""(07(-98:4+;+

(4) %-

(5) 4%<!-

(6) " "("=?>@+

(7) AB7CC EDF+*0 %'-%0 5GH% @%B %! "!

(8) -@+*-

(9) "(

(10) H"IJK8L +M"N"(C(-O=6PF+F-

(11) "

(12) HF"QR

(13) F-

(14) "

(15) HF

(16) -,"Q-

(17) H$-, " +RHS7JH(-;UT

(18) GIJ%?0 5VH%'01""(0W %X"F07T%%'

(19) YIJK8LZ[8\0CC%B %'"?01 R"]134?'+%01C-,-

(20) T%']^,01""=NPF+?

(21) %']

(22) 4&34_0 5& `C

(23) &#" +

(24) L+^

(25) %0 I&I&]34K<Y0 5aH%01""]bc0W %`

(26) H%' "("_ "\+:+d<7" 3-

(27) "(

(28) H "3% %= e G+

(29) \

(30) %'"(dV+""^ %' 3U,+07-G5f0 %N0 I

(31)

(32)

(33) :H017$-&H_IJ01T

(34)

(35) -

(36) " 0 56+g"(C(Y5f0 %:+-

(37) "

(38) HGIJK8L9+gC%B %'"":-%X4W -O=FPF+ ,+

(39) 0U-) "'"T

(40) ,"#+

(41) G+,0 %'-%RIJK8L)+

(42) %B %'"h]"#BU0i8:O=,PF+ ,+

(43) 0U-2+

(44) "hIj2&&34-9(0A'+

(45) %01,01"(01,k.T

(46) YIJ%hlmZ0 5\+

(47) "0bK 334#no%X=GPF+ 3T

(48) 301

(49) "#+

(50) W ,IJp-01*q9&3 &-9+

(51) g0 %X-%#0 5 +G ":"?0 I& -;T

(52) "',q9q9B %= PF+R Y9-&"(

(53) HR8? ":"(-;(0kIJRrdsU=ut tCH.q90 %1 8:+Z"(

(54) -

(55) %'-A-WU]401;vU=wm1sH.q90 %1 O= x "(&%'(Z

(56) %'0 I&34y"(T

(57) -

(58) 4-zz++""Z{c|UH01~}1g"g+

(59) 0 5:&/b "( "'"D&,5f0 %'0 5

(60) G.(%' H401O=LQ&" ""`"F"' -Z(0C07T%F8^+Z+ H01YI&-HjHQ0 5J[8\0h0 %\,0 %F "_H01T

(61) 3-0 Q+&W :IJ

(62) %'-

(63) H(-, " +"T

(64) 0 5Q+4%"(&%'(gHJH"=EW 3"0 56+g13T

(65) H01"(gH01

(66) Hd(%X401 +I&340U0U-+

(67) W Z&-

(68) (-)+&Y&]"( ""g< 0UT%, 01&%g0 5 X+%01,01"(01YUT

(69) GIJ%h#0 5N+h%X= PF+

(70) 9+.<.J0 +"]",0 5G -

(71) -

(72) 4WUK<{017bc&",+A13]T

(73) H01"(9]

(74) H% "( ":("((-950 %^+G34W 3":0 5N13T

(75) H01"(tUT("F &-9vmCC.T

(76) ("F5(%#7b H401O=L0 %:+G13T

(77) H01"(G3W 3a5(%gt].T("?"( ""F0UT%:I&T`+ +.<.J0 +"'"N0 5O017bc&"? "Q5f0 %Q+:13T

(78) H01"(:3W 3

(79) 5(%?vmhUT(" H01T

(80) 3]-;0 ÌJR% H(-O=. .

(81) .

(82) !#"$ "%'&()+*,-. / 02]1 346587976:<;=?>@5BA8CD4E1F1G1F1G1G1F11G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 H I !#"$ "%KJ (ML L N , O P]1 QSRUTWVX;YDZ[:\58;7 1G1F1G1G1F11G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 ] P21 8]1 ^`_CFabRUc\dRU;CefX;YDZ9:<58;g1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 h P21 81i0 ^`_CFj 587[RUkml:efX;YnZ[:\58; 1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 po P1i0 q)7NZ[:<kgRrZ9:<58;s5Ue$Z[_CG46CtYD58kul:\;RrZ[:\58;vef49RUYDZ9:<58;w1F1G11F1G1G1F1G1F1G1G1 U P1xP q)7NZ[:<kgRrZ9:<58;s5Ue$Z[_CG=UCt;CnZ[:<Y kgRUTyd:\76ZzRr;YtCK1G1F1G11F1G1G1F1G1F1G1G1 U P21iP]1 {-RU46:|RU;YDC 5Ue$Z[_CGabRrc<dRU;CefX;YDZ9:<58; 1F1G11F1G1G1F1G1F1G1G1 B0 P21iP1i0 {-RU46:|RU;YDC 5Ue$Z[_CGj 587[Rrkul:%efX;YnZ[:\58;}1F1G11F1G1G1F1G1F1G1G1 B0 P21iP1xP q)76Z9:<kgRrZ[CDd~kgRUTyd:\76ZzRr;YtC 1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 pP P21iP1 q)76Z9:<kgRrZ[CDdyArRU46:|RU;YtCt75UeRu_58c\C Yz_4958k587658kgC1F1G1F1G1G1 pP P21iP1i QS:\;:<k:<79RrZ[:\58;v5Ue$Z[_CArRU46:|RU;YtC1G1F1G1F1G11F1G1G1F1G1F1G1G1 t P1 q)7NZ[:<kgRrZ9:<;=Z[_Cu46CtYD58kul:\;RrZ[:\58;Sef49RUYDZ9:<58;WRU;d:Z[7ArRU46:|RU;YtCuX76:<;= c\:<rCtc<:\_552d71G1G1F1G1F1G1G1F11G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 B S6("-"(MLN(M "6 ( ) ]1 CpRrcdRrZzR 1G1G1F1G1F1G1G1F11G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 p] 1i0 )4658lRUl:\c<:Z[:<CD75UeYt465879765BA8Ct467 1G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1 p] 102]1 QS:\7979:\;=RU;d~:<;YD58kTc<CnZ[CdR?ZzR1G1F1G1F1G11F1G1G1F1G1F1G1G1 ph S6(". (% ¡¢£.¤-."¥ ¥&F"$§¦¨ ¦.© 2]1 q)7NZ[:<kgRrZ9:<58;s5Ue$Z[_CG=UCt;CnZ[:<Y kgRUTyd:\76ZzRr;YtCK1G1F1G11F1G1G1F1G1F1G1G1ª0U 21i0 q)7NZ[:<kgRrZ9:<58;s5Ue$Z[_CArRU46:|RU;YtCef584«Z9_C=8Ct;CnZ[:\Y d:<7NZzRU;YDC1G1F1G1F1G1G1ª0U¬ 21xP 35UkgTRr49:<7658;7«:Z[_SQWRUT+QSRUUCD4 1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1PUo WL N()N ® H]1 ^$Ct7NZ[:\;=ef5U4`CtT:\76ZzRr79:<7¯1G1G1F11G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1P80 H1i0 °;RUc±276:<;=¯Z9_C58l79CD46ArRrZ9:<58;7~1G1F1G1F1G1G1F1G1F1G11F1G1G1F1G1F1G1G1PUP ² ³ +* $´¶µ" ,."$"$ « ® · ¸"¹"" " ®.O º »¼$¼)½¾¿$ÀfÁÂ I+º 0.

(83) »¼$¼)½¾¿$ÀfÁ¢. P. .

(84)

(85) CD;CDZ9:<Y kgRUTT:\;=u5Ue$=8CD;Ct7:<7«RU;y:<kT 584NZzRU; Z49Ct76CpRU46Yz_~Z9525Uc:<;s=UCt;CnZ[:<YD7t1 Ct;CnZ[:\Y kvRUTT:<;=yCD;RUlc\Ct7GRs=8Ct;C Z[5yl£CRU7976:<=8;CDd Z95~R~Yz_4658k587958kC RU;d Z[5~RyT 5U79:\Z9:<58; 49Ctc<RrZ[:A8CmZ95s5UZ[_Ct4=8CD;Ct7 :Z[_:\;WZ[_C¯79RUkCuYz_495Ukg587658kCU1^`_:<7b:<7 R 4676Z7NZ[CtT :\; Z[_CF:<dCD;Z9: YtRrZ[:\58;SRU;dW:\7958c<RrZ[:\58;s5Ue)=UCt;CD7 RU797652YD:|RrZ9Ctd~:\Z[_~_CD49Ctd:\ZzRr46±~d:<76CpRU76Ct7D1 °«ZFZ9_C CtTRU4NZ[kCt; ZG5Ue«QS58c<CDYtXc<RU4GQSCDd:<YD:<;C RrZGjRU4658c<:\;79? R @;7NZ[:Z[XZ9 C $=8Ct;CnZ[:\Y 76Z[Xd:<CD7G5re.Z@±T£Cv0d:<RUl£CDZ[CD7 :<;49RrZ[7:<7bd58;Cr1

(86) ;Z9_C¯«Rp±5U e ;d:<;=Z9_C =8Ct;CD7 Z[_RrZgR CtYnZgZ9_CydCDAUCtc\58TkCt; Zv5rebZ@±T CW0d:|Rrl CnZ[Ct7gR=8Ct;CDZ[:\YSkgRUT 5UeZ[_C~4[R?Z 7 =8Ct;5UkgC:<7-kvRrdCU1 _Ct;vZ9_Cb49RrZ 7-=8Ct;5UkgC_RU7-l CDCt;kgRUTT£Ctd Z[_Cb:<dCt; Z[: YpRrZ9:<58; RU;d :<7658c|RrZ9:<58;S5UeMZ[_C¯=UCt;CD7FR CDYDZ[:\;=Z[_C¯dCDAUCtc<5UTkgCD; ZF5re-Z@±T£Cg0vd:|RUl£CDZ9Ct7 YtRU; l C kgRUdCr1)°«ZjGRr4958c\:<;76rR @;76Z9:\Z[X2Z[CR¯Yt58kTXZ9Ct4«TRUYz?RU=8CYpRUc\c<CDdyQWRUT+QSRUUCD4_Rr7 l CDCt; X79Ctd _Ct; dCtYD:<d:\;=sZ[_C 5846dCt45Ue-Z[_C=UCt;CD7mRU;d Z9_C d:<7NZzRU;YDCt7Gl CnZ@CDCt; Z[_CDkS1 ^`_C~49RrZ 7¯=8CD;58kCs_RU7¯l£CtCt; kgRUTT£Ctd lXZ Z9_Csd:<7NZzRU;YtCt7 l£CDZ@.CtCD; Z[_C =8Ct;CD7Rr49CCt7NZ[:<kgRrZ9Ct7 8Z9_CYt584649CDYDZ-d:<7NZzRU;YtC:<7);5rZ.;5B;%1)° XCD76Z9:<58;g5Ue:\; Z[Ct46Ct7NZ :<7`_5BKkuXYz_SX;YtCt4NZzRU:\;yd:<7NZzRU;YDCCt76Z9:<kgRrZ[CD7RU49Cr1 ^`_:<75846~RU:<k7RrZ ;d:\;=RU;WRU;7NCD4bZ[5 Z[_:\7 XCD76Z9:<58; £: 1CU1 ;d:<;=RgkCDZ9_5d Z[5WCD76Z9:<kgRrZ[C Z[_C76Z[RU;dRr49d dCnA:|RrZ9:<58; 5Ue«Z9_Cvd:\76Z[RU;YtCl£CDZ@.CtCt; =8CD;Ct7D1y^5 ;d Z[_CsArRU49:<RU;YDCC 4676Z _RpA8CyZ[5 CD76Z[:\kvR?Z[CvZ9_Cs=8Ct;CDZ[:\Ysd:<7NZzRU;YtCU1 CyRU46C~=U58:<;= Z[5sCt7NZ[:\kvRrZ9CmZ[_C¯d:<7NZzRU;YDC RU;d7NZzRU;dRU49d dCnA2:<RrZ[:\58;5Ue-Yz_4658k587958kCu;Xkul£Ct4G0ro 5UeZ9_Cy4[RrZt1 ^`_CykgR 2:<kuXk¯>@c\:<rCtc<:\_552dkCDZ9_52d :\7¯X79CDd Z95 CD76Z9:<kgRrZ[CvZ9_CykvRrT d:<7NZzRU;YDCU1M^`_CD79C YpRrc<YtXc|RrZ9:<58;7-RU7679XkCbZ9_RrZZ9_C5846dCt45UeZ[_CbkvRU46UCD49"7 !f58lZzRr:<;CDd X79:\;=QSRUT+QWRUrCt$4 #:\7`Yt584649CtYnZp1 °e Z[CD4~Z9_C 4[RrZ x7~Yz_4658kg5U7958kC;Xkul£Ct4 _Rr7Sl£CtCD;§kgRUTT£Ctd 58;C TRU4NZS5remZ[_C Yz_4958k587658kgC_Rr7l£CtCD;W:<7658c|R?Z[Ctd1.^`_CD49CFRU49CG4[R?Z[7`Z[_R?Z_RBAUCFZ9_CF79RUkCG=UCt;5UZ@±T£C RU7RG_CpRrc\Z[_ ±¯49RrZ.%C 2YtCDTZef584)Z9_C:\7958c<RrZ[CDd TRU46Z _:<Yz_v_RU7-Z9_C7[RUkC=8Ct;5rZ@±2T£CRr7 Rgd:<RUl CnZ[:\YG49RrZp1`^`_Cm4[R?Z[7:Z[_yZ[_:\7Yz_4958k58795UkvRUcTRU46Z YtRUc<c\Ct'd &:<ddk p(R 79_5B RU; :\;Yt46CpRU76Ctd =Uc<XYD5879C c<CnA8CDc-YD58kTRU49CDd :Z[_ Z[_C;58;>@d:<RUl CnZ[:\Y¯4[RrZ97t1RrZ97G_RBAUC l CDCt;Yt495U7979CDdgX;Z9:<cZ[_Cn±u58;c±m_RBAUCRUTT46)5 2:\kvRrZ9Ctc±F5U;C`_RUce+5Ue+Z[_C`Yz_4658k587958kgRUc TRU46*Z &:<ddk p+R !fZ9_Cu76kvRUc\c<CD4TRU46Z97 RU49CmYpRUc\c<Ctd &:\dd k plRU;,d &:<ddk t-: #n1^`_CD79C 4[RrZ97-_RBAUCR;58;2> d:|Rrl CnZ[:<Y=8Ct;5rZ@±2T£C%C 2YtCDTZef584Z9_CTRU46Z9 7 &:<ddk tl5U.4 &:<ddk t: 1 ^`_ C XCt7NZ[:\58; 5Ue«:<; Z[CD49Ct7NZu:\7GZ95W79CDCv:e«Z[_C4[R?Z[7F:Z[_ Z[_C_58c<CTRU4N/Z &:<ddk BR _RpA8CGRU;y:<;YD49CtRU79CDd~=Uc<XYD5879C c\CDA8CD.c !¡YD58kTRU49CDds:\Z[_Z9_C ;58;>@d:<RUl CnZ[:\Yb4[R?0Z #-Z9_RrZ:<7 Z[_C`79RUkgCRU7Z9_C«79Xk¥5UeZ9_C«:<;Yt49CtRU79CDd¯=8c<XYt5876C«c<CnA8Ctc\7ef584$Z[_C«49RrZ[7:\Z[/_ &:<ddk tl RU;d &:<dd k p: 1 CRU; ZZ95FZ[CD76Z`:1e &:<dd k plgRU;d &:<ddk p:+Rr49CRUdd:Z[:\AUCU21 _Ct; d58:<;=S0C T£Ct46:<kCt; Z[7Z[_C=Uc<XYD5879CYt58;YtCt; Z94[RrZ9:<58; _RU7Gl CDCt; kgCtRU79X46Ctd yRU;d PUo kg:\;X2Z[Ct7uRre Z[CD4m:<4; 36CtYDZ9:<58; RU;d 58;Cv_RU7ud:\79YD5 AUCt46Ctd Z[_R?ZuZ[_Cv4[RrZ97m:\Z9_ Yz_495Ukg5r> 7958kgRUc)TRU4NZ &:<ddk t:)_RpA8CgRS_:\=8_Ct4=8c\XYt5U79C c<CnA8Ctc-Rre Z9Ct;4 skg:\;XZ[CD7GZ9_RU; 4[RrZ97 :\Z[_ Z[_C_58c\CgTRr465Z &:<ddk pR1 625~Cv79X76T CDYDZmZ9_Rr5Z &:\dd k pl Rr;d &:<dd k p: .

(87) UR 49C;5UZ`Rrdd:\Z9:\AUCU12 CRU46Cb=85U:<;=Z[5GZ[Ct7NZ«Z[_Cb_ ±T 5UZ9_Ct76:<7«5reRUdd:Z[:A2:Z@±¯:<;g=8c<XYt5876C :<;YD49CpRr79C5UeZ9_C Z@5TRU4NZ[7&:\ddk plyRU;d'&:\ddk p: 1 3_RUTZ9Ct4v0 :\7gR 79_5846Zg:<; Z[4652dXYDZ9:<58; Z[5 Z[_CS=8CD;CDZ9:<YylRUYz=84658X;d1 @;¶3_RUTZ[CD4 PgZ[_CFT49:\;Yt:\Tc<CG5Ue)=UCt;CnZ[:<YFkvRrTT:<;=v:<7T46Ct79CD; Z[Ctdef58c\c<5B.CtdWl ±S_5B'Z[_CF=8Ct;CnZ[:\Y d:<7NZzRU;YDCWYtRU;l C~Ct7NZ[:\kvRrZ9Ctd%1 _CD;dCpRUc\:<;= :\Z9_¢46CpRUcdRrZ[R Z[_CT49:\;Yt:\Tc<Cy:\; 3_RUTZ9Ct4-PYpRU;;5UZ)l£C`X79CDd d:<46CtYDZ9c\±U1^`_CD49CRU49C49Ct7NZ[46:<YDZ9:<58;7:<;mZ9_C`%C 2T£Ct46:<kCt; ZzRUc kgCnZ[_5d7¯RU;d 7958kCDZ9:<kCt7G58l76Ct46ArRrZ9:<58;7¯RU49Cgkg:\7976:<;=~584m:\;Yt5UkgTc\CDZ9CU1a5B¤Z9_:<7 :<7 ZzRUrCt; YtRU49C5Ue:<7%C 2Tc<RU:<;CDd :\; 3_RUTZ9Ct4m1v°«ZZ[_CCt;d 5Ue`3_RUTZ9Ct4m( Z9_Ct46C :<7gRU;¢0C RrkgTc\CS5re_5B Ct7NZ[:\kvRrZ9Ct7_RpA8Cl£CtCD;¶kgRUdCU1¢^`_CCt7NZ[:\kvRrZ9:<58;7¯5UeZ[_C kvRUTvd:<7NZzRU;YD C AURr49:|Rr;YtCbRU;ds76Z[RU;dRr49dsdCnA2:<RrZ[:\58;v5reYz_4958k587658kgC;Xkul£Ct40UoF5Ue Z[_Cu49RrZ Rr49CmT49Ct76Ct; Z[CDd :<;3_RUTZ[CD4 £_:<Yz_CD;d7:Z[_RgYt58kTRU46:<795U;S:\Z9_WZ[_C Ct76Z9:<kgRrZ[CD758lZzRr:<;CDdSX76:<;=vQWRUTQWRUUCD4t1 @;W3_RUT2Z[Ct4H¯Z[_CZ[CD76Z:\2e &:<ddk tlSRr;d &:<dd k t:RU49CRrdd:\Z9:\AUC :<7«Z[46CpRrZ9Ctd%1. .

(88) !#"$ "%&()£*,- Centromeres. V :<=8X46C!

(89) "!$#% &' "'( @;_Ct49:Z[CDdvZ[49RU:\Z97RU46CbdCnZ[CD49k:<;CDdl ±gZ9_Cb=8CD;Ct7 _:\Yz_sRU49Cc<5YpRrZ9CtdvRUc<58;=FZ[_C Yz_4958k587658kgCD7t1q-RrYz_u=8Ct;C5YtYtXT:<CD7R.Ctc\c> dC ;Ctdu76:\Z[C UYtRUc<c\CtdFRc<5YtX7 !fTc 1$c<5Yt: #n1 ° Yz_495Ukg587658kCmYt5U;79:\76Z[7b5Ue)58;CmYz_4958kgRrZ9:<dRr;d58;CmYtCt; Z94958kCt46CU*1 @;CnA8Ct4N±YDCtc<c Z[_CD49CsRU46CvZ@.5Yz_495Ukg587658kCt7mZ9_RrZu_RBAUCvZ[_C7[RUkCv=UCt;CnZ[:<Ygc<5Yt:-RU;d 7NZ[46XYDZ9X49C 58;C¯:<;_Ct46:\Z[CDdef4958k Z[_Cue¡R?Z[_CD4RU;d 58;C¯:\;_Ct46:\Z9Ctdef495Uk Z[_C¯kg5UZ9_Ct4D1m^`_CuZ@.5 Yz_4958k587658kgCD7sRU46CYpRUc\c<CDd¢_58k58c\58=858X7Yz_4658kg5U7958kCt7D1K^`_Ct46C RU49CRrc\RB±7vZ@.5 ef5849k75Ue.Z9_C7[RUkC =8Ct;C YtRUc<c\Ctd RUc\c<Ctc\Ct7D1 eZ@.5W=8CD;Ct7FRU49C c\52YtRrZ[CDd :\; d: Ct49CD; Z Yz_4958k587658kgCD7 $Z[_Cn± Rr49Cv:\;_CD49:\Z9Ctd :<;dCtT£Ct;dCD; Z[c\± 5Ue«CpRUYz_ 5rZ[_CD4t1~qA8Ct; :\eZ@.5 =8Ct;CD7Rr49Cc<5YpRrZ9Ctd 58; Z[_C79RUkgCYz_4658k587958k C :ZM:<7M;5UZMYDCt4NZzRU:\;Z9_RrZMZ[_Cn±u:<c\cl£C :<;_CD49:Z[CtduZ958=8CnZ[_CD4)l CDYpRUX76CdX49:\;=Z[_C«ef5849kgRrZ[:\58;m5re£Z9_C`790C YtCDc<c\7 UZ9_C`= RUkCDZ9Ct7 RU;W0C Yz_RU;=8Cu5re79CD=8kCt; Z[7ef4958k Z9_CGZ@.5_5Ukg58c\58=858X7`Yz_4958k587658kgCD7YtRU;W5YtYDX4t1 ^`_:<7%C 2Yz_Rr;=8CG:<7`YpRrc<c<CDdyYt495U7979:\;=r> 5 AUCt4D1 ¦ )6 +,.-/0/pÀ¡2¾ 1435-76£½ , * X49:\;=skgCD:<5876:<7 Z[_Cuef5849kgRrZ[:\58;W5re-Z9_C¯790C YDCtc<c\7 %CtRUYz_ Yz_4958k587658kgCmdXTc\:<YpR?Z[Ct7 RU;dyZ[_CD;SYD58;79:\76Z975reZ@.5gYz_4958kgRrZ[:\d7`YpRrc<c<CDds79:\76Z[CD4Yz_4958kgRrZ9:<d7D1)^`_C Z@5Yz_495?> kvRrZ9:<d7RU46C 3658:\;CtdmRrZR79:<;=8c<CMYtCD; Z[495UkgCD49CU1°e Z[CD4Z9_CYz_4658k587958kCt7_RpA8C«dXTc<:\Yn> RrZ[CDd Z[_C_58k58c\58=858X7 Yz_4958k58795UkgCD7Gef5846k}TRU:\497GRU;d Z9_C ef58X4GYz_4958kgRrZ9:<d7GRU46C c<:<;Ctd~XTSZ958=8CDZ9_Ct4ef5846kg:\;=R AUCt46±~Z[:\=8_ ZlX;dc\ C +YpRrc<c<CDdWR¯Z[CnZ[49RUd £79CtCmV:<=UX49ZC 81 @;~7658kCTc|RrYtCt7 2Z9_C Yz_495UkvRrZ9:<d7.:<; Z[CD4976CtYDZCtRUYz_y5UZ[_Ct4`RU;ds:<;vZ9_Ct76CGYD49587679CD7 Z[_C Yz_4958kgRrZ9:<d7YpRU;¯l46CpRU+.1 65258;uRre Z[CD4Z[_CYz_4958kgRrZ9:<d7_RpA8C`l4658UCD;uZ[_Cn±¯RU46C«c<:\;UCDd Z[58=8CnZ[_CD4¯RU= Rr:<; lXZuZ9_:<7Z[:\kgC :\Z9_ RW;58;>@79:\76Z9Ct4mYz_4958kgRrZ[:\d%1~^`_:<7F:<7mYtRUc<c\Ctd R Yt495U79795BAUCt4t1M°e Z[Ct4-R Yt465879765BA8Ct4._RU7M5YtYtX4949CDd Z[_CYz_4658kvR?Z[:<d7MRU49C`k: Z[X49Ct7M5Ue£Z[_C 5849:\=8:<;RrcTRU49CD; ZzRUc$Z@±2T£Ct7D1°«ZbZ9_5C 4676ZbYtCtc\cd:\A:<76:<58;SdX49:\;=vkCt:\5879:\7CtRUYz__58k5r> c<58=85UX7TRU:<476CtTRU49RrZ[CD7t1`^`_CD;WZ[_CFYDCt; Z[4658kgCD49CF79Tc\:\Z[7RU;dSZ[_CF76:<76Z9Ct4Yz_495UkvRrZ9:<d7 79CtTRU4[RrZ9CU1s°«ZGZ[_C79CDYt58;d YtCDc<cMd:\A:\79:<5U; CpRUYz_ = RUkCDZ[C 46CtYtCD:\AUCt7m5U;Cg5reZ[_Cgef58X4 Yz_4958kgRrZ9:<d7D,1 62CtCyV:<=8X46Ct7u0y>H1V+X46Z[_Ct4udCnZzRU:\c<7GYpRU; l£Cvef58X;d :<; aRU46Z9cRr;d 8 58;Ct5 7 !'ph8h8] #¹1 H. Sister chromatids.

(90) V:<=UX49CG07. '#' '

(91) "!$#% '(. . #5& '&'# '$# (. V:\=8X49CP7. . V:<=8X49C4. 7 # '(. #" ' "

(92) ! "!$#5 #% ' 7# .

(93) . V:<=UX49CG 7. . V:<=8X49C H . !$#% ! '

(94) #% ! 7#% "'(. "!.

(95) '#% ' &" ! 7#"!$#% '(. ¬.

(96) #! "$ "%'J (ML L N , CD;CDZ9:<YkgRUTT:\;=mTc|RUYDCt7«=8CD;Ct758;sYz_495Ukg587658kCt725849dCt49:\;=mZ9_Ctk¤:<;46Ctc<RrZ[:\58;gZ95 CpRUYz_ 5UZ9_Ct4mRU;d Ct76Z9:<kgRrZ[CD7F=UCt;CnZ[:<Ygd:<7NZzRU;YtCt7GZ[5Rrd39RUYtCD; ZuTRU:\497D1~^`_CvlRU76:<7F5Ue =8Ct;CnZ[:\Y«kvRrTT:<;=b:<7Z[_C«T49:\;Yt:\Tc<CMZ[_RrZZ9_C«T4658lRUl:\c<:Z@± 5Ue+Yt46587976:<;=?>@5BA8CD4l CnZ@CDCt; Z@5 =UCt;CD7g:\;Yt46CpRU76Ct7g_Ct;¢Z9_CST_±76:<YpRrcd:<76Z[RU;YDCSl£CDZ@.CtCD;¶Z[_CDkE=8CDZ97gc<RU49=8CD4t1 ^`_Cu=8CD;CDZ9:<YGd:<7NZzRU;YDCml£CDZ@.CtCD; Z@.5c\52YD::<7dC ;Ctd RU7Z[_CG%C 2T£CtYDZ9Ctd ;Xkul£Ct45Ue Yt495U79795BAUCt49752YDYtX4649:\;=`l CnZ@CDCt;GZ[_CDk 58;GR`79:<;=8c<CYz_4958kgRrZ9:<d dX46:<;=kCt:\5879:\7t1^`_:\7 :<7)_RUce+Z[_C;Xkul£Ct4M5Ue %C 2T£CtYDZ9CtdgYt495U79795BAUCt497.l CnZ@CDCt;vZ9_C`c<5Yt:2ef584MR_58c<C«Z9CDZ94[RUd%1 ^`_CX;:\Z5UeZ[_C =UCt;CnZ[:<Ybd:<7NZzRU;YDC :<7«YtRUc<c\CtdsR Q~5849= Rr; :\;sT4[RUYnZ[:\YtCYDCt; Z[:|QS5849=8RU; :<7bX79Ctd1 ^`_Cu%C 2T£CtYnZ[Ctd ;Xkul£Ct45UeMYt465879765BA8Ct46758;Rvd:\76Z[RU;YtCF5UeM58;C¯QS5849=8RU;:<7 58;CU1-3465879765BA8Ct467YtRU;;5rZ«l£C58l76Ct46AUCtd~d:<46CtYnZ[c\ ± 2lXZ«.CYpRU;s5Ul79CD46A8C:e%Z[_Cb=8Ct;CD7 RrZgZ@.5 kgRU49rCt467 "!¡R kgRU49rCt4kvRU467vR c<5YtX$7 #%«Rr49C~49CtYD58kul:\;RU; Zg584g;5UZp1¶^«.5 kvRU46UCD497 RU46C49CDYt58kul:<;RU; Zm:\e58;Cs:\7mkgRrZ[CD49;RrcRU;d Z9_C5UZ9_Ct4m58;C:\7uTRrZ9Ct49;RUc 1 e Z[_Cn±¶RU46CW46CtYt5Ukul:<;RU; Zv.C;5B Z9_RrZRU;¶5dd¶;Xkul£Ct45re Yt465879765 AUCt467~_RBAUC 52YDYtX4649Ctdl£CDZ@.CtCD; Z9_Ctk~1 e)Z@.5skgRU49rCt497RU49CF;58;2> 49CtYD58kul:\;RU; Z £;5sYD495876795BA8CD497. Locus 1. Locus 1. Locus 2. Locus 2. V :<=8X49CF¬7 ' ' #% #% ' ( ' '

(97) #5 #% ' ( 584RU;yCDA8CD;W;Xkul£Ct45UeYt465879765BA8Ct467b_RpAUCGZ[RUUCD;WTc<RUYtC79CDCmV:\=8X46CG¬21 ® )6 ¼ $¾ À -£¾ / ^5Ct7NZ[:<kgRrZ9CMZ9_CM=8Ct;CDZ[:\YMkvRUTd:\76Z[RU;YtC r_:\Yz_F:\7Z[_CM7[RrkgC-RU7Z[_C.0C T£CtYnZ[CDdu;Xk > l CD45UeYD495876795BA8CD497 8R`kvRrTefX;YDZ9:<58; :\7;CtCDdCtd1° kgRUTefX;YnZ[:<5U; :<7R«kgRrZ[_CDkvR?Z[:<YtRUc 49Ctc<RrZ[:\58;76_:<TZ[_RrZGYt58; A8CD46Z97ukvRrT d:\76Z[RU;YtC ! #Z[5~49CDYt58kml:<;R?Z[:<5U; ef49RUYDZ9:<58; ! #n1 @; V:<=8X49Ct70 >@HZ[_Ct49C52YDYtX^4 Yt465879765BA8Ct4MRr;dmZ[_Ct49C«RU49C«05UeZ9_C46Ct79Xc\Z[:\;=b=8RUkgCnZ[CD7 Z[_RrZYt5U;Z[RU:<;7bR49CtYD58kul:\;RU; ZYz_495UkvRrZ9:<d~: 1CU1«5U;CF_RUc\e5UeZ[_CF= RrkgCnZ[Ct7D1`^`_:<7:<7 Z[49XCFef584RU; ±~;Xkul£Ct45Ue)Yt465879765BA8Ct467 %5ddS584CnA8CD;%1 e)58;CGYt465879765 AUCt45YtYDX497:<;SR Z[CDZ94[RUd Z[_Ct49CgRU46Cg58;c\±Z@.55Ue.Z[_C ef58X4GYz_495UkvRrZ9:<d7 Z9_RrZFRU49C49CDYt58kml:<;Rr;Z 765 Z[_CuT4958lRrl:<c\:\Z@±s5Ue=8CDZ6Z[:<;=Rv46CtYt5Ukul:<;RU; ZbYz_4658kgRrZ[:\dW:<7 1 eZ9_Ct46Cu_RpA8Cml CDCt; Yt495U79795BAUCt497RrZ«Z@.5Tc|RUYDCt7 Z[_CD49CRU46CCt:Z[_CD4ef58X4`Yz_4958kgRrZ[:\d7.:Z[_s58;C Yt495U79795BAUCt4 ] (a) One crossover. . . . . . (b) Two crossovers. . . . .

(98) pC RUYz_ 584 Z@5SYz_4958kgRrZ9:<d7:Z[_ Z@5SYt495U79795BAUCt497uRU;d Z@5~:\Z[_ ;5~Yt465879765 AUCt4D1 @; Z[_C 497NZYtRU79CRrc<cYz_4658kgRrZ[:\d7-RU49C49CDYt58kml:<;Rr;ZRU;d:<; Z[_C79CDYt58;dYpRU76C;58;C5Ue Z[_CDk¥:<749CtYD58kul:\;RU; Zp1 C`76XTT£5879C«Z9_RrZZ9_C«Z@.5GT£587679:<lc<C5UXZ[YD58kgCD7MRU49CCXRUc\c\± c<:<rCtc± $795SZ9_CvT4958lRrl:<c\:\Z@±5re«=8CnZ9Z[:\;=SRS49CDYt58kml:<;Rr;ZFYz_4658kvR?Z[:<d :<7 1s^`_Cg49C¹> Yt58kul:<;RrZ9:<58;uef49RUYDZ9:<58;¯l£CDZ@.CtCD;vZ@.5Fc\52YD::<7Z9_CT4958lRUl:<c\:\Z@±Z[_RrZ)Z[_C`Z@.5mc\52YD:RU46C 49CtYD58kul:\;RU; Zp1)^`_CbkgR 2:<kuXk¥49CtYD58kul:\;RrZ9:<58; ef4[RUYnZ[:\58;vl£CDZ@.CtCD;Z@5¯c\52YD:58;vZ[_C 7[RUkC`Yz_495Ukg587658kC«:<7 21 e£Z9_Ct46C:<7)RrZc<CpRr76Z)58;C`Yt495U79795BAUCt4-l CnZ@CDCt;gZ@.5c<5Yt: rZ[_C T4958lRUl:<c\:\Z@±S5Ue.58l79CD46A:<;=WRy49CDYt58kul:<;RrZ9:<58;:\7 1g^`_C46CtYD58kul:\;RrZ[:\58;ef4[RrYDZ[:\58; ! #0:<7«Z9_Ct46CDef5846C 0 _Ct46C :<7Z[_CuT4958lRrl:<c\:\Z@±y5Ue-RrZbc<CtRU76Zb58;CmYD495876795BA8CD4:<;WZ9_CFZ9CDZ[49RUd%1 CDZ l£C Z[_CT4658lRUl:\c<:Z@±F5re ;5GYD495876795BA8CD4 Z[_CD; 21 e .C79Xl7NZ[:Z[XZ9C :Z[)_ CG_RpA8C !'4# 0 ! # ^`_Ct46C¯%C 2:<7NZ[776CDA8CD4[RUcd: Ct46Ct; ZkgRUTefX;YDZ[:\58;7Z[_RrZRUc<c_RpAUC¯d: Ct46Ct; ZbArRUc\XCt758; 1 C_RpAUCG7NZ[Xd:<CtdyZ@.5g5Ue$Z[_Ctk Z[_CGaRUc<dRr;CkgRUTsefX;YDZ9:<58;~RU;dSj 5879RUkul: x7 kvRUTsefX;YDZ[:\58;% 1 62CDCmRrc<795 6_RUk !Bh8h8P #¹1 I f

(99) f ½ ¿ ¾½ $¾ À -£¾ ^`_CmaRUc<dRU;CefX;YnZ[:\58;~RU7976XkgCD7`Z[_RrZ`Z9_C52YDYtX4649CD;YtCD7b5UeYt465879765 AUCt467b58;~R¯Yz_495?> kvRrZ9:<d RU46CRG$58:<767958;gT495YtCD797):\Z9_g:\; Z[Ct;79:\Z@p± 81^`_C:<; Z9Ct;76:\Z@±¯:\7)58;Cl CDYpRUX79Cl± dC ;:\Z[:\58;Z[_Ct49C5YtYDX49758;C YD495876795BA8CD4T£Ct4`kgRUTyX;:Zp1 CnZ`Z[_C4[Rr;d58k¤AURr49:|Rrlc<C l£CZ9_C;Xkul CD4m5UeYt465879765 AUCt467u:<; R~Z9CDZ[49RUd%1^`_CgkgRUT d:<7NZzRU;YD C ! #%$:<7Z[_C %C 2T CDYDZ9CtdW;Xkml CD45reYD495876795BA8CD49758;~RuYz_4958kgRrZ9:<dyRU;dy;5rZ:<;yRu_58c\CZ[CDZ94[RUd1)° Yt495U79795BAUCt4`58;5U;CbYz_4658kgRrZ[:\dv49CD79XcZ[7«:\;gZ@.5uYt465879765BA8Ct467:<;gZ9_C_58c<CZ[CDZ94[RUd 2Z[_C Yz_4958kgRrZ9:<dv_RU7.Z95m%C 2Yz_Rr;=8C76Ct=8kCt; Z«:Z[_Rr;5UZ[_Ct4Yz_4958kgRrZ[:\d 795GZ[_C0C 2T CDYDZzR > Z[:<5U;uef584 :\7M0 1^$5=8CDZ)RU;¯%C 2T46Ct7976:<58; ef584$Z[_C`=8CD;CDZ9:<Y«d:<76Z[RU;YDC`:<;uZ[CD49k75Ue+Z[_C 49CtYD58kul:\;RrZ9:<58;Wef49RUYDZ9:<58;.C ;CtCDd Z95s;5B /1 62:<;YtC :<758:\79795U; d:\76Z949:<lXZ[CDd :\Z[_~%C 2T£CtYnZzRrZ9:<58;S0 Z9_CT4958lRUl:<c\:\Z@±g5Ue;5 Yt495U79795BAUCt4b:\7 ! o # o ! @;79CD46Z[:\;= Z[_:\7`:<; Z[5q XRrZ[:\58~ ; F=U:\A8CD7`Z[_CGabRrc<dRU;C kvRUTsefX;YDZ[:\58; #" $ 0 :\Z9_~:\; A8Ct4679

(100) C %" ! # 0 c\1; !$ 0 # !0 # h.

(101) I f

(102) \ ½ - / À ¾ À -£¾ abRUc\dRU;Cx7ukgRUT efX;YDZ[:\58; RU7679XkCt7uZ9_RrZuZ9_Ct46C:<7m;5:<; Z[CD46efCD49Ct;YtCsl£CDZ@.CtCt; Z[_C Yt495U79795BAUCt497 .: 1xCr1WZ[_RrZuYD49587679:<;=r>@5BA8CD4u:<; 58;C46Ct=8:\58; 5UeRYz_4958k58795UkgCd5Ct7u;5rZ 49CtdXYtC Z[_C¯T4958lRrl:<c\:\Z@±~5Ue.Rs79CtYD58;d Yt465879765 AUCt4G:<; Rs;CtRU49l ±46Ct=8:\58;%1uj 5879RUkul: x7 kvRUTefX;YDZ[:\58; RU7679XkCt7 Z[_RrZ:<; Z[CD46efCD49Ct;YtC C%2:<7NZ[7:<;Z9_C 79CD;79C Z[_R?Z 49CDYt58kul:<;R?> Z[:<5U;7mRr49CX;c<:\UCDc\±Z[5S52YDYtX4GYtc\5879CZ[5SCpRUYz_ 5rZ[_CD4t1y^`_:<7GkCpRU;7Z[_RrZF_Ct; Z[_C kvRUTd:\76ZzRr;YtC:<7M79kgRUc\c UZ9_C49CtYD58kul:\;RrZ9:<58;¯ef49C XCt;Yn±vC XRUc<7)Z9_CkgRUTd:<7NZzRU;YtCU1 @;j 587[Rrkul: 7kvRrTyefX;YDZ9:<58; Z9_CG:<; Z[CD46efCt46Ct;YDCFdCtYt46CpRU76C¯RU7R c<:<;CpRU4«efX;YDZ[:\58;~5Ue Z[_Cd:\76ZzRr;YtCr1-^`_Cmj 5879RUkul:%kgRUTsefX;YnZ[:\58;y:<7 0 :Z[_~:<; A8CD4979

(103) C ! # c\1; ! 00 # !P # @; V:<=UX49C]~.C76CtCgZ9_RrZuabRUc\dRU;C x7efX;YnZ[:<5U; =8:A8Ct7mRS_:\=8_CD4FCD76Z[:\kvR?Z[C5Ue«Z[_C. . Map distance. Haldane’s function. V:<=8X49Cu]7

(104) ! #%'. . Kosambi’s function. Recombination fraction. %# ' '

(105) ' " ! #% ' # & ' ' ' (. kvRUTyd:\76Z[RU;YtC Z9_RU;Sj5U7[RUkul: 1. po.

(106) ® )@¦ / À À - ¾ -

(107) $½ , ½ -À ¾ À -£¾ , À -£¾ ^5SCt76Z9:<kgRrZ[C¯Z9_C =8Ct;CnZ[:\YgkgRUT d:<7NZzRU;YDC¯C497NZm;CDCtd Z[5~Ct76Z9:<kgRrZ[C¯Z9_Cg46CtYD58k > l:<;R?Z[:<5U;ef4[RUYnZ[:<5U;yRU;dsZ[_CD;sCYpRr;SX76CGR kgRUTefX;YDZ[:\58;Z[5 58l2ZzRU:\;yRU;yCt76Z9:<kgRrZ[C 5UeZ9_C kgRUTd:\76ZzRr;YtCr1 CnZ`Z[_C 49RU;d58k¤ArRU49:<RUlc<Cl Cou:e$Z@.5 79T£CtYD:CDd~c\52YD::\; :<;d:A:<dXRrc «RU49CF;58;2> 49CtYD58kul:\;RU; Z Rr;d ¯:\eZ[_Cn±RU46Cu49CDYt58kml:<;Rr;Zt1b^`_C¯T4958l2> RUl:<c\:\Z@±y5Ue-R46CtYD58kul:\;RrZ[:\58;~:<7 1 ^`_Cu4[Rr;d58k ArRU49:<RUlc<C :<7Z[_CD; R Ct46;58Xc\c<: AURr49:|Rrlc<Cr.1 62XTT£5876CG.CF5Ul79CD46A8 C :<;d:\A:<dXRUc<7 2.CZ9_Ct;S_RpA8CG58l76Ct46ArRrZ9:<58;7«ef4958k.

(108) Ct46;58Xc\c<:MAURr49:|Rrlc<CD7 1 ^`_Cs79Xk ª5reZ9_Ct76CsAURr49:|Rrlc<CD7m:<7ml:<;5Ukg:<RUc d:<7NZ[49:\lXZ9Ctd : 1xCr1 ! #n1s^`_CQ >@Ct7NZ[:\kvRrZ9C 5Ue y:<7 1s^`_Cg%C 2T£CtYDZ9Ctd AURrc<XC 5Ue ~RU;d Z[_C ArRU49:<RU;YDC5re !" !' #n1 _Ct#;. :<7«c<RU49=8$C _RU7`RU;~RUTT495 2:<kgRrZ[C;5846kvRUc£d:\76Z[46:<lX2Z[:<5U;v:\Z9_Z[_C 0C T£CtYnZzRrZ9:<58;yRr;d AURr49:|Rr;YtCbRUl 5BAUCU1)^`_C46CtYD58kul:\;RrZ[:\58; ef4[RUYnZ[:<5U;vRUc\795F_RU7`RU;vRUTT465 :\kvR?Z[C;5849kgRUc d:<7NZ[49:\lXZ9:<58;yRU;d~Z9_CCt76Z9:<kgRrZ[CD7`5Ue$Z[_C49CDYt58kml:<;R?Z[:<5U;ef4[RUYnZ[:<5U;s:<7 % &% RU;' d ( )% !$ # !¡ # ® ) ® / À À - ¾ -

(109) $½ 1+½2¾½ À ¼¿À / ¾ 8½ Cs;5Bª_RpA8CyCt7NZ[:<kgRrZ9Ct7u5UeZ9_Cs49CDYt58kul:<;RrZ9:<58; ef4[RUYnZ[:<5U; RU;d l ± X76:<;=Z9_+ C *B> kgCnZ[_5dv.C YpRU;s=8CnZ`Ct7NZ[:\kvRrZ9Ct7.5UeZ[_Cb%C 2T CDYDZ[RrZ[:\58;yRU;dArRU46:|RU;YDCef584-Z[_Cb=8Ct;CnZ[:\Y kvRUTmd:<7NZzRU;YDCU1^`_C«Ct7NZ[:<kgRrZ9CtdukgRUTud:\76Z[RU;YtC 8X76:<;= RkgRUTmefX;YDZ9:<58; :\7 % ! #n1 C.58Xc\dsc<:<rCZ95¯;5 , !- #. 1 eC X79C ^RB±c\584«%C 2TRr;79:\58;yRrZ / F.C _RpA8C ! # ! # ! # 10 ! # 32 ! # °b7976Xk:<;=Z[_R?Z¶YtRU;l C;CD=8c<CDYDZ[CDdRU;dZ[RU:<;= Z[_C0C T£CtYnZzRrZ9:<58;5Ue Z[_C49CDkvRr:<;2> :<;= %C 2T46Ct7679:<5U;W=8:A8Ct7 ! .# 546 ! # ! # 10 ! #. ! #7 ! # 10 ! #7 ! #7 10 ! # ! # ! # 89 ! #. 795GC;5B _RpA8C Rr;vC%2T46Ct7679:<5U;ef584: ! #7 1)^RU:<;=FZ[_C. UR ;d ! # AURr49:|Rr;YtC5Ue%Z9_CC%2T49CD7976:<58;:\;q.XR?Z[:<5U;s =8:\AUCt7.RU;vC0T49Ct7679:\58;gef584MZ[_CArRU46:|RU;YDCU1 ;<5=>@?BA= <5CED ! 7# 54 8!! #7 . U. !H #.

(110) !¡79CDC.c<58k !'Bh8]Uh # #¹1. ! 7# 4 7 10 !/ ! # #7 . !¬ #. I \I f 4,?À¾8½ - ½ ¿¾½ $¾ À-£¾ :\Z[_vabRUc\dRU;Cx7.kvRrTgefX;YnZ[:\58; ! # %" ! % # c<;!'0 % #% %% " %"! % # RU;d %% " 54 0 c<; !' 0 # !] # ^5=8CDZRU;y0C T49Ct7679:\58;Sef584«Z9_C ArRU49:<RU;YtC.CG;CtCDd " ! ! % # # " ! #«RU;d %" 0 ! # $ 0 @;79CD46Z[:\;=¯Z[_:\7«:<;.q XR?Z[:<5U;~¬m=8:\AUCt7Z9_C ;RUc%C 2T49CD7976:<58;sef584Z9_CbArRU46:|RU;YDC5UeZ[_C abRUc\dRU;CefX;YDZ[:\58; %" 545 )7 10 " ! #. !' !$ 0 # # RU;dyZ[_CCt7NZ[:\kvRrZ9CtdsArRU49:<RU;YDC 5UeZ9_C=8Ct;CDZ[:\YkvRUTyd:\76Z[RU;YtC :\7 % % !h # %% " 54 ! % #. !$ 0 # I \I \ 4,?À ¾ 8½ - ½ - / À ¾ À -£¾ 79:\;=j 5879RUkul: x7«efX;YDZ9:<58;~=8:\AUCt7 !- # ! # ! . #0Ct7NZ[:<kgRrZ9Ctd~l± % *! % #%:\Z9_y%C 2T CDYDZ[RrZ[:\58; % 54 c<; ! $ 00 # !'Bo # ^`_CFdCt49:ArRrZ[:A8C 5Ue *! #:<7 ! # RU;dyZ[_C ArRU49:<RU;YDC 5Uej 5879RUkul: x7`kgRUTsefX;YnZ[:\58;y:<7 4

(111) 5 )7 10 ! #7 !'( !' # # _:<Yz_~:<7Ct7NZ[:\kvRrZ9Ctdsl ± % % ( % 54 !$ % # !'74#. !' # B0.

(112) I \I \I / BÀ B½¿ ¼¶¿À/ ¾ 8½ 62XTT£5879C.C`Rr49C5Ul79CD46A:<;=Z[_C.7[RUkCYz_4658k587958kC-58; v49RrZ[7$:\Z9_ .58l76Ct46AUCtd kvRU46UCD497G58; Z9_CgYz_4958k58795UkgC d:A2:\d:<;=s:\ZG:<; Z[5 :<; Z[CD46ArRUc<7! Z[_Cc<CD;=UZ9_7F5reZ[_C Ct;d 76Ct=8kCt; Z[7¯YtRU; ;5rZ¯l CgCt7NZ[:<kgRrZ9Ctd #¹1W°ª46CtYD58kul:\;RrZ[:\58; _RU7u5YtYtX4949CDd :<; RU; :<; Z[CD46ArRUc:eZ[_CZ@.5 Ct;d75reZ[_C :\;Z9Ct4NAURrc_RpA8C76Ct=8kCt; Z[7«ef4658k¤d: Ct46Ct; ZTRU46Ct; ZzRUc Yz_4958k587658kgCD7t1 CDZ o :\e:<; Z[CD46ArRUc M:<;s49RrZ g:\7`;58;2> 49CtYD58kul:\;RU; Z :\e:<; Z[CD46ArRUc M:<;s49RrZ g:\7`49CtYD58kul:\;RU; Z RU;d ,! Z[_CuZ95UZzRUc;Xkul£Ct4 5Ue-49CDYt58kml:<;R?Z[:<5U;7ef584RUc<c 4[RrZ97`:<;s:<; Z9Ct46ArRU5c #¹1)^`_Ct; :\7 CD49;58Xc<c<:£d:\76Z[46:<lX2Z[Ctd:Z[_yTRU49RUkCDZ[CD4 /!fZ[_C 49CtYD58kul:\;RrZ9:<58;mef49RU% YDZ9:<58; #RU;d l:\;58k:|RUc :Z[_¯TRU49RUkCDZ[CD497 yRr; d @1^`_CQ > Ct76Z9:<kgRrZ[C5Ue :<7 Rr;dvZ[_CbCt7NZ[:\kvRrZ9Cb5UeZ[_CkvRUTgd:<7NZzRU;YtCbef584 :<; Z[CD46ArRUc «:<758lZzRr:<;CDdWl ±W:\;79CD46Z9:<;= % :<; Z[5Z[_CukgRUTefX;YDZ9:<58;%1^`_CuCD76Z9:<kgRrZ[CF5Ue Z[_C=8CD;CDZ9:<YkvRrT~d:<76Z[RU;YDC:Z[_sZ[_CFaRUc<dRU;C kgRUTsefX;YDZ9:<58;sZ9_Ct;~:<7 % " 0 c\; !' 0 # !' 0 # QS5849CD5BA8Ct4 £Z9_CYt584649CD79T£58;d:\;=¯efX;YDZ9:<58;sef584j 5879RUkul: x7`kgRUTsefX;YnZ[:\58;y:<7 % c<; ! $ 00 # !'BP # ^`_CCt7NZ[:\kvRrZ9:<58;5UeZ9_Cbc\Ct;=UZ9_v5UeZ9_C_58c<CYz_4958k587658kgCd:A2:\dCtdv:<; :<; Z[CD46ArRUc<7 :<7.Z9_Cb76Xk¤5Ue%Z[_Cd:<7NZzRU;YtCt7.5Ue$RUc\c£:\; Z[Ct4NArRUc<7 1)^`_CkgRUTvd:<76Z[RU;YDC :<7RUdd:\Z[:A8C lX2ZZ9_C49CDYt58kul:<;RrZ9:<58;ef49RUYDZ9:<58;s:\7;5UZp1 I \I / BÀ B½¿ 6 ,rÀ ¾ 8$½ / -

(113) - ¡½ ,.- - / - ½ ^`_C¯AURr49:|Rr;YtCF5UeMZ[_C¯CD76Z[:\kvR?Z[CtdWkvRUTd:<76Z[RU;YDCmef58458;C¯:<; Z[CD46ArRUcRU7 dCD49:A8Ctd :\; 62CtYnZ[:<5U;SP21iP1)^`_CArRU46:|RU;YtC5UeZ9_C c<CD;=UZ[_y5UeZ9_C_58c\C Yz_4958k587658kgCb:<7Z9_C 79Xk 5UeRUc\cAURr49:|Rr;YtCD7-ef584-CpRrYz_:<; Z[CD46ArRUc l£CtYtRUX76C49CDYt58kul:<;RrZ9:<58;7):<;vd:<7 365U:<; Z-:<; Z[CD46ArRUc<7 RU49C RU7679XkCtd :\;dCtT£Ct;dCt; Zp1m^`_C Ct76Z9:<kgRrZ[CDdArRU49:<RU;YtCm5UeMZ[_C¯c\Ct;=UZ9_5Ue.Rv_58c\C Yz_4958k587658kgC:Z[_ kvRr49UCD497X76:<;=abRrc<dRU; C 7kgRUTsefX;YnZ[:\58;y:<7 . . . . . . . . . . . . . .

(114) . . . . . . . . % " . . . ! # !' 0 # . . . ^`_:<7C%2T46Ct7679:<5U;WYpRr;Sl£C 49:\Z6Z[CD;~:\;sZ[Ct46kg7`5reZ9_CkvRUTyd:\76Z[RU;YtCGRU7 ! 4# % " pP . . . . . . . !'p #.

(115) 79:\;=gj5U7[RUkul: 7efX;YnZ[:<5U;y.CG_RpA8CZ[_CCt7NZ[:\kvRrZ9CtdsArRU49:<RU;YDC ! # ( % ! ! # # ^`_CGArRU46:|RU;YtC YpRr;Sl£C 49:\Z6Z[CD;~:\;sZ[Ct46kg7`5reZ9_CkvRUTyd:\76Z[RU;YtCc\:<UC ! P # ! 4# ! 4# % !' # HU I \I \ 'À ¾$À À / À - ¾ -

(116) $½ 6 4,?À ¾ 8½ ^`_Cm76: tCF5UeZ9_CFArRU46:|RU;YtC5UeZ9_CmCD76Z[:\kvR?Z[Ctd~kgRUTSd:<76Z[RU;YDCFef584R_58c<CGYz_495Ukg5r> 7958kCArRU49:\Ct7«:\Z9_y;Xkul CD4`5UekvRU46UCD497t1M^`_C ArRU46:|RU;YDC RUc\795¯dCDT CD;d758;y_5B§Z[_C kvRU46UCD497RU49C76YpRrZ6Z[Ct46CtdWRUc<58;=uZ[_CYz_4658kg5U7958kCU1 ^`_C79X=8=8Ct7NZ[:\58;v:\7-Z9_RrZMZ[_CArRU49:<RU;YtCD7)ZzRUrCZ[_Ct:<4Mk:<;:\kuXkAURrc<XCD7-_CD;vZ[_C d:<7NZzRU;YDCt7Gl CnZ@CDCt; Z9_C kvRr49UCD497GRU46CC XRUc 1 e.Z[_C¯efX;YnZ[:\58; 5re.Z9_C¯AURr49:|Rr;YtC :<7 Yt58; A80C ~CGYpRU;~X76C 8 CD;79CD; 7b:<;C XRUc\:\Z@±81 . . . . . . . . . . . . . . . . . = = . =. . .

(117). ]. . e ! #v:<7yR Yt58; A8C0 efX;YnZ[:<5U;§RU;d o bZ[_CD; ! E # ! # 2! # ! E #n1 e ! # o¯:<;~RU;~:<; Z[CD46ArRUc Z[_CD; ! #:<7`YD58; A8C%S:\;yZ9_C:<; Z[CD46ArRUc 1 ^`_CGArRU46:|RU;YtCef584aRUc<dRr;C 7èfX;YDZ9:<58;y:\7 ! -# ! 4#% o1 ^RU:\;=4976ZRU;d~76CtYD58;dWdCt49:ArRrZ[:A8Ct7`±:<CDc<d7 ! # RU;d ! # C79CtCZ[_R?Z ! -# oGef584-RUc\c 2! )# :<7MYD58; A8C%gef584.RUc<c o1°bYtYD5849d> :<;=¯Z[5 8 CD;79CD;x 7:<;C XRUc<:Z@± . . . . . ". . . !. . . . . . . $#. . !. . %. . . . !. . . $#. &. . . $(. . . E ! 4# ! # . Z[_Ct; 81 C Z9_Ct;S_RpA8C . . . ). . *. . . . e.CGYz_525876C. +. . . '. . 2! 2! 2! ! . . . . . . . . !. . . . #. # ## . . . . . t. 2! # . . 2! # . .

(118) _Ct46C :<7`Z[_C76Xk 5Ue)Rrc<c%:\;Z9Ct4NAURrc<7: 1CU1 8 Ct;76Ct;7b:\;CXRUc\:\Z@±gZ[_RrZ . . . . ! . . . . . . 4#. . . . 1 Zef58c<c\5 7.ef4958k . . ! # . `^ _Cuk:<;:\kuXkªArRUc\XCm5UeZ[_CmArRU46:|RU;YtCFef5U4baRUc<dRr;C 7efX;YDZ[:\58;WZ9_X7:<758lZzRr:<;CDd _Ct;Z[_Cd:<7NZzRU;YDCl£CDZ@.CtCt; Z[_CkvRr49UCD497s:\7vCXRrc 1K^`_CC0T49Ct7679:\58;ef584vZ[_C AURr49:|Rr;YtCZ9_Ct;S:<7 ( %% " ! 4# . ^`_CGArRU46:|RU;YtCef584j 5879RUkul: x7«efX;YDZ[:\58;y:<7 ! # HU ! P #! 4# ! )# o ! # ] ! # !' P #`RU;d P 4# ! ! # . @;mZ[_:\7YtRU79C -! # o_Ct; o o U(P ?lXZ ! -#:\7YD58; A8C0mef584 o o UP1 @; Z9_Cu79RUkgCF«Rp±Rr7bef584aRUc<dRU; C 7befX;YDZ[:\58; £Z[_CuArRU46:|RU;YDCFZ[RUUCD7 :\Z[7kg:\;:<kmXk AURrc<XC_Ct;gZ[_Cd:<7NZzRU;YtCl CnZ@CDCt;Z[_CkgRU49rCt467:<7MC XRUc T495BA:<dCDdgZ[_Cd:\76Z[RU;YtCD7 RU49Cl:\=8=8Ct4«Z9_RU;~o1xo UP1)^`_CArRU46:|RU;YtC :<7 % HU ! P #! )# ! 4# o o8 UP ® )¡ / À À¡2¾ 1 $ ½ , ½ - À ¾ À -£¾ , À -£¾ ¾$¿ À ./ 6 4,?À ¾ 8½ 2/pÀ¡2¾ 1 ¡À +½ ¡À - -2 ¿/ eZ[_Ct49CgRU46C:\;Yt5UkgTc\CDZ9C¯584kg:\7979:\;=sdRrZ[RyZ9_Ct; Z[_CgCD76Z[:\kvR?Z[C¯5Ue.Z[_C 49CDYt58kml:<;2> RrZ[:\58; ef4[RrYDZ[:\58; :\; 58;Cs:\;Z9Ct4NAURrc.dCDT CD;d7 58; Z9_CsCt7NZ[:<kgRrZ9Cv:<; RU;5UZ9_Ct4u:\; Z[Ct4NArRUc 1 e.Z9_:<7:\7bZ[_C¯YpRU76CuZ[_C¯46CtYt5Ukul:<;RrZ[:\58;7:\;CpRUYz_ :<; Z9Ct46ArRUcYpRU; ;5rZ l C¯CD76Z9:<kgRrZ[CDd 58;C RrZRvZ9:<kCU*1 @;7NZ[CtRUd .C¯_RpA8C¯Z95sX79CuZ9_C¯c<:\UCtc\:<_55d~ef584Z[_Cu5UXZ[YD58kgCm5Ue.RUc<c :<; Z[CD46ArRUc<7D1 CnZFZ9_Cgc\:<rCtc<:\_552dWef5U4Z9_C 49CDYt58kul:<;RrZ9:<58; :\; :\;Z9Ct4NAURrc :\; 49RrZ Wl£C uRU;dZ[_C Z949XC¯46CtYD58kul:\;RrZ[:\58;Wef49RUYDZ9:<58;ef584b:<; Z[CD46ArRUc `l£. C @1m^`_Cc\:<rCtc<:\_552d ef584 :\;Z9Ct4NAURrc<7b5U;WZ[_CmYz_4958k587658kgCm:<;W49RrZ s:<7Z[_CD;Z[_CuT49 5dXYDZ B1 ° _58c<CdRrZ[RU79CnZ«:\Z9_dRrZ[RFef4958k S4[RrZ97_RU7.Z[_Cc<:<rCtc\:<_552d ! #¹ 1

(119) ;C «Rp±Z[5GkvR 2:\kg:\79C«Z[_:<7Mc<:\UCtc\:<_55d¯:<7)Z[5Fd: Ct46Ct; Z[:<RrZ[C`Z[_Cbc<:\UCDc<:<_525dm:\Z9_v46Ct79T£CtYnZ B . . . . . . . . . . . ). . . . . . . . . . . . . .

(120) . . . . . . . . .

(121) Z[5CtRUYz_ `Rr;d CXR?Z[CvZ9_Ctk}Z[5 tCt4651 CZ[_CD; _RpA8CsR~76±76Z9Ctkw:\Z[_ CXR > Z[:<5U;7YD58;79:\76Z9:<;=F5Ue X;;5 ;sArRU46:|RUlc\Ct7 ! #¹1 6258c\A:\;=GZ9_:<7.76±76Z9Ctk5Ue C XRrZ9:<58;7m=8:\AUCt7FZ9_CvCD76Z9:<kgRrZ[CDd 49CDYt58kml:<;R?Z[:<5U; ef4[RrYDZ[:\58;7D1~^RU:<;=WZ[_Cg;RrZ9X4[RUc c<58= Rr49:\Z9_k}5Ue`Z9_Csc<:\UCtc\:<_55d l£CDef5U49CvZ9_Csd: Ct46Ct; Z[:<RrZ[:\58; 76:<kTc<:Ct7Z[_CYt58kTX2> ZzRrZ9:<58;7D1^`_CuYD5BAURr49:|Rr;YtCukgRrZ949: ~5re)Z[_CuCD76Z9:<kgRrZ[CDd49CDYt58kul:<;RrZ9:<58;~ef4[RUYnZ[:\58;7b:\7 l CDYpRUX76C5reZ[_CYDCt; Z[49RUcc<:\kg:ZZ9_Ct5U49Ctk Z[_C:\;AUCt4679C5Ue Z9_C:<;ef5U49kgRrZ[:\58;ukgRrZ[46: m5Ue Z[_Cc<:\UCDc<:<_525d 79CDCGj:\CDefCD4 !'Bh8]8¬ #n1^`_CG:\;ef5846kvRrZ9:<58;kgRrZ[46: g:<7R l ± kvR?Z[49: _Ct46CFZ[_CGCDc<CDkgCD;Z:\;~465B RU;dSYD58c<Xk+; 2 RU;d :<7`Z[_C c<:<rCtc\:<_552dvd: Ct46Ct; Z[:<RrZ[CD d 497NZ:Z[_y49CD79T£CtYnZZ95 RU;dsZ[_CD;~:Z[_y49CD79T£CtYnZZ95 kg:\;Xg7 81^`_CbArRU49:<RU;YtC5Ue%Z9_Cb=UCt;CnZ[:<YkvRrTvd:\76ZzRr;YtC:<7MZ[_CD;s58lZzRr:<;CDdvl ±X79:\;= Z[_+C *p>@kCDZ9_52d ef584mk5849CgZ[_CD; 58;C49RU;d58kwArRU49:<RUlc<C 76Ct+C c\58k !'Bh8]Uh #%_:\Yz_ :<7dCD49:A8Ctd :<;SZ[_C¯79RUkgCF«Rp± RU7Z9_C *p>@kCDZ[_52dWef5U458;CuArRU46:<lc\CF0C YDCtTZGZ[_RrZZ[_C ^Rp±c<5840C TRU;79:\58;~:<7`kgRUdC:\Z9_ykg5846CZ[_CD;S5U;C AURr49:<lc<CU1 . . ;<5=>@?BA= <5CED ! % % % #.54 . . . . ! # ! # . pH. . . . ! % % # . . !'BH #.

(122) S 6("-y"¤(ML(M "6 ( ^`_CRU:<k 5reZ[_Cb_58c<C7NZ[Xd2±:<7-Z[55;d_:<Yz_s=UCt;C584«=UCt;CD7Z9_RrZ«:\;Yt46CpRU76Ct7`584 kvRp±l CdCDYt49CtRU79CD7FZ9_Cg46:<765UeZ@±T£C0sd:<RUl CnZ[CD7t1gRrZ97G:Z[_ ;5B; T_CD;5UZ@±T£Ct7 RU49C X76Ctd :<;Z[_C0C 2T CD49:<kCt; Z97t1¯^$5 ;dZ[_C =8CD;Ct7 Z[_RrZ CRU46C¯c<558:<;=gef584 %.C 497NZ;CtCtdSR¯=8Ct;CDZ[:\YkgRUTy5 AUCt4`Z[_C 4[RrZ x7`=8CD;58kCU1)^$5 d5¯Z[_:\7 RU ; :\; Z[Ct46Yt4658797 :<7kvRrdC l CnZ@CDCt; Z9_C 5UZ95r>jRU: tRU: ! j #4[RrZGRr;d Z9_C ;5849k58=8c± YtCt;:<Y VPUU 4[RrZ 79CDCV:\=8X49Cgh1~°b; >@:\; Z[Ct46Yt4658797F:<7FRWl49CDCtd:\;=Wl£CDZ@.CtCD; Z@5_5Ukg5 n±=85UZ[C :<;d:A:<dXRrc<7FRU;d Z[_CZ@.5 :<;d:\A:<dXRUc<7FRU49Cv_58k5 D±=858X7mef584ud: CD49CD;Z¯RUc<c\Ctc<CD7m:\; Z[_C7[RrkgC c\52YD: 1^`_C j49RrZ`_Rr7l£CtCD;S76Ctc\CtYDZ9Ctd~dX46:<;2= Bo¯=8CD;Ct49RrZ[:\58;7D1 @;~CtRUYz_ =8Ct;CD4[RrZ9:<58;¯Z9_C Bo 5re Z9_C4[RrZ97MZ9_RrZM_RpAUCZ9_C_:<=8_Ct76ZM=Uc<XYD5879C`YD58;YtCD; Z[4[R?Z[:<5U;g:\; Z[_C`lc\525d RU46C«X79CDdvRr7)TRU49CD; Z[7)ef584Z9_C`;%C Z-=8CD;Ct49RrZ[:\58;%1^`_:<7=8:A8C«Z9_C j 4[R?ZMR T_Ct;5UZ@±T C _:<Yz_76_5B7`Yz_RU49RUYDZ9Ct49:\76Z9:<Yt7-Z@±T:<YtRUc 5reZ@±2T£C0Fd:|RUl£CDZ9Ct7t1^`_C VPUU 4[RrZd52CD7;5rZp1^`_C«4[RrZ97_RpAUC«l CDCt;¯:\;l49CtCDdCtd¯X;Z9:<cRUc\c_RBAUCZ[_C«7[RUkC=UCt;5UZ@±T£Ct7D1 . . . Homozygote female with genotype AA Parents. Genotype at locus 1 Genotype at locus 2. Heterozygote male with genotype AB. Heterozygote female with genotype AB A|B A|B . . A|B. A|B A|B . . A|B. F1 generation. Homozygote male with genotype BB B|B B|B . . B|B. A|A A|A . . A|A. F2 generation A|B B|A . . B| B. A|B A|A . . B|B. A|B A|B . . A|B. .......... ........... V :\=8X49Ch7 '#%'#5& '( ^`_C j#49RrZ-:<7)_5Ukg5 n±=858X7-RU;d_RU7MZ[_C79RUkC=UCt;CnZ[:<Y`Z@±T£C:\; Z9_C_58k58c<5U=858X7 Yz_4958k587658kgCD7t1 ^`_CyVPUU4[RrZu:<7¯RUc\795_58kg5 D±=858X7mlXZ¯:\Z9_ RU;5UZ9_Ct4m=8Ct;CnZ[:\Y Z@±2T£CU1 CDZRUc\c£=UCt;CnZ[:<YZ@±T CD7«:<;Z[_C j 49RrZ.l CYpRUc\c<Ctd°b°§RU;dZ[_C=8Ct;CnZ[:\YZ@±T CD7 :<;vZ9_CVPU8F4[RrZ«l CYpRUc\c<Ct d b1^`_C 5 76T49:\;= Z[_C =8Ct;Ct4[R?Z[:<5U,; !'76Z[RU;d7«ef584 B¬ . . . A|B A|B . . A|B.

(123) c|RrZt1c\:<X7 7658;RU;d ukCpRU;7Z[_RrZb:\Z:<7Z[_C54976ZbT495U=8Ct; ±(#%%5re-R j 49RrZ RU;dR VPU8u49RrZ`:\7.Z[_Ct;y_CDZ9Ct465 D±=858X7«:\Z[_v=8Ct;5rZ@±2T£C °$13495U79795BAUCt497:<;v_58k5 D±=858X7 4[RrZ97ud5;5UZuYz_RU;=8CZ9_C=8CD;CDZ9:<YvZ@±T£Cs5Ue`Z[_Cs= RUkCDZ[CD7ml£CtYtRUX79CsZ9_C79CD=8kCt; Z[7 _:<Yz_ RU49C%C 2Yz_RU;=8Ctd :eYD495876795BA8CD497u5YtYDX4 RU46C5reZ[_Cg79RUkgC =8CD;CDZ9:<Y¯Z@±T Cr1 C ;5 ÂZ[_RrZ5U;C5Ue%Z9_C_5Ukg58c\58=858X7-Yz_4958k58795UkgCD7:<7.:<;_Ct49:Z[CDdgef495UkZ9_C jK4[RrZ RU;d58;Cèf4958kZ[_CVPUUG49RrZp1^`_Ct46CbRU46C;5kg: 2Z9X49CD7M5Ue Z9_C=8Ct;CnZ[:\Y«Z@±2T£Ct7.:<;¯Z[_C Yz_4958k587658kgCD7t1)a5BCnA8Ct4 2Z9_CT4958=UCt; ± 5Ue£Z[_C =8CD;Ct49RrZ[:\58; 8Z[_C =8CD;Ct49RrZ[:\58; _RU7-RGk: Z9X49C«5re%=8CD;CDZ9:<Y«Z@±T CD7.5re°ÂRU;(d :<;¯Z[_C79RUkCYz_4958k58795UkgC T495BA:<dCDd Z[_RrZbYt465879765 AUCt467G_RU7bZzRrUCt;Tc|RUYDCU$1 .CtYpRrX79Cm.C¯YpRr;WZ[CDc<cZ[_CFd: Ct46Ct;YDCul CnZ@CDCt; Z[_CZ@5S=8Ct;CnZ[:\YZ@±T£Ct7 °ªRU;d Z[_Cg46CtYt5Ukul:<;RrZ[:\58; ef46C XCD;YD± l CnZ@CDCt; Z@.5 c<5Yt:%:\;yZ9_C =8Ct;Ct4[R?Z[:<5U;~YtRU;~l C 58l79Ct4NA8CDd%1 )6 ½ .¿ ^`_C«ef5849kmXc|RU7:<; 6CtYDZ9:<58;uP10Rr;d 62CtYnZ[:\58;¯P1xPbef584YtRUc<YDXc|R?Z[:<;=Z[_C«49CDYt58kul:<;RrZ9:<58; ef4[RUYnZ[:<5U;gRr;dZ9_CkvRrTd:<76Z[RU;YDCYtRU;;5rZ.;5849kgRUc<c±Gl CX76Ctdvd:<49CDYDZ9c\±u5U;g46CpRUcdRrZzR1 @;76Z9CpRUd~Z[_CCt7NZ[:\kvRrZ9:<58;7«d:<76YtX7679CDdW:<' ; 62CDYDZ9:<58;SP1YtRU;~l C X76Ctd%1 ^`_C¯=UCt;CnZ[:<YuZ@±T£Ct75UeMZ@.5S_5Ukg58c\58=858X7bYz_4658kg5U7958kCt7 Rr49C RUc«Rp±7 58l76Ct46AUCtd Z[58=8CnZ[_CD4t1 eZ[_C.=8Ct;CnZ[:\Y-Z@±T£Ct7)RrZ58;C.c<5YtX7RU46C.°¢RU;d ?.Cd5b;5UZ;5 _:\Yz_ 58;Cu5Ue)Z9_CFZ@.5sYz_4658kg5U7958kCt7Z[_RrZbYpRU4646±WRUc<c\Ctc\CG°¥RU;dW_:<Yz_Z[_RrZYtRU494N±WRrc<c<CDc<C b1 CDYpRUX79C¯5UeMZ[_:<7.C¯d5;5UZ ;5B¥:eZ@.5~c\52YD:;%C Z Z[5vCpRUYz_ 5UZ9_Ct4bZ9_RrZbl 5UZ9_ _RpA8Cu=8CD;CDZ9:<Y Z@±T CD7$° #RU49CG49CDYt58kml:<;Rr;Z584;5UZt1«^`_CD49CmYD58Xc\dWl£CF;5U;CF5U4Z@.5 49CtYD58kul:\;RrZ9:<58;7D1)^`_:<7`:\7`;5UZ`Z9_C58;c\±vT495Ulc<CDkS.1 658kgCnZ[:\kgCD7`:\Z`:\7`58;c\±vT 5U7979:\lc<C Z[5 58l76Ct46AUCGZ9_C=8Ct;CDZ[:\YZ@±T C5Ue58;C Yz_4658k587958kCU1)^`_CG:\;ef5846kvRrZ9:<58;g:<7«Z9_RrZ`Z[_C c<5YtX7:<7Ct:Z[_CD4_5Ukg5 n±=858X7ef584Z9_Cm5Ul79CD46A8CDd RUc<c\Ctc\C 584_CDZ[CD495 n±=858X7 %YpRU4646±:<;= l 5UZ9_ RUc<c\Ctc\CF°RU;d b1%^`_CD49C¯:<7RUc<765sRT 5U7979:\l:<c\:\Z@±sZ9_RrZ Z[_Ct49C Rr49Cuk:<7679:<;=dRrZ[R ef584`7958kC:<;d:\A:<dXRUc<7RrZ7958kCc<5Yt: 1 )@¦ ,.- À ¡À À¡$½ / - ,.-/0/'-76£½ ,&/ CnZ l CFZ[_C¯T4658lRUl:<c<:Z@±y5Ue-R49CDYt58kml:<;R?Z[:<5U;Wl£CDZ@.CtCt; c<5YtX 7 %[c %Rr;dc<5YtX7 0 c|02 1 e`Z[_Cg=8CD;CDZ9:<YZ@±2T£Ct7mRrZFc gRU;d c|0~RU46Cg°5° Z[_CD; Z9_Cvl£5UZ[_ _58k58c<5U=858X7 Yz_4958k587658kgCD7RU49CG;58;2> 49CDYt58kul:<;RU; Zl£CDZ@.CtCD;WZ[_CZ@.5vc<5Yt: 1)^`_CGT4958lRUl:<c\:\Z@±v5Ue Z[_:\7m:< 7 !' # 1W^`_CsT4658lRUl:<c<:Z@±:<7GZ[_Cg7[RUkCv :e«Z[_C=8Ct;CDZ[:\YgZ@±T£Ct7 RU46 C b1 ^`_CT4658lRUl:\c<:Z@±Z[_R?Zmc|0y:\7 :\e`[c g:\7F°°ª:<7 $Z[_Cgl 5rZ[_ Yz_4658k587958kCt7FRU46C 49CtYD58kul:\;RU; Zp1 Ct;CnZ[:\YgZ@±T CD7u°b°¤:<; c vRU;d ° ¥:<; c 0s:<;d:<YpR?Z[Ct7Z[_RrZFZ9_Ct46C:<7 58;C49CDYt58kul:<;RrZ9:<58;v:<;s58;C5UeZ9_C Z@5Yz_495Ukg587658kCt7 795¯Z[_CD49CGRU46CZ@5T 5U7979:\lc<C 49CtYD58kul:\;RrZ9:<58;7uZ9_RrZ=8:A8CZ[_:<7 49CD79XcZp1 ^`_C~T4958lRUl:<c\:\Z@± Z[_RrZYz_4958kgRrZ9:<d Q !¡kgRrZ[CD49;RUc #:<7M46CtYt5Ukul:<;RU; Z-RU;dYz_4958kgRrZ9:<d !fTRrZ[CD49;Rr-c #:<7);5UZ-:<7 ! #¹1)^`_C T4958lRUl:<c\:\Z@±¯Z9_RrZ«:\;76Z9CpRUdv5Ue$Rm49CDYt58kml:<;R?Z[:<5U;v:<;gYz_495UkvRrZ9:<dQRm49CDYt58kul:<;RrZ9:<58; :<;Yz_4658kgRrZ[:\dv 5YtYtX497«:\7.Z[_Cb7[RrkgC (!' #¹1)^`_CT4658lRUl:<c<:Z@±¯5Ue%Z9_Cb76C XCD;YtC p] . . . . .

(124) Locus 1, AA. Locus 1, AA. Chromatid M. Chromatid P. Chromatid M. Chromatid P. Locus 2, AB Locus 2, BA ~ .

(125) '

(126) ! '

(127)

(128) ' #5 #%"'

(129). V:<=8X49C Bo.

(130) .

(131) . . !$ #% #%"'

(132)

(133) . °°5°$ :<7Z[_CD;WZ[_CF76Xk. (. U5 eZ[_Ct79CFT495UlRUl:\c<:\Z9:<CD7_:\Yz_:<7CXRrc$Z950(!'$ #% 79CtCuV:<=8X49C;Bo1`^`_:\7:\7;5UZZ9_CmYtRU79CF:\ec G_RU7Z9_Cm=UCt;CnZ[:<YZ@±T CF°$#RU;dc|0 _Rr7 Z[_Cg=8Ct;CnZ[:\YgZ@±T Cv°b°m1^$5=8CnZmZ[_Cv=8CD;CDZ9:<Y Z@±2T£C°° RrZFc<5YtX7m0 $Z[_CD49C:\7F58;c\± Z[_CYz_4958k587658kgC`Z9_RrZ-YpRU4649:\Ct7.RUc<c\Ctc<C ¢RrZ-c<5YtXY7 Z[_R?ZYtRU;vl£C46CtYD58kul:\;RU; Z Z[_C T4958lRUl:<c\:\Z@±g:<7`Z[_Ct49Cnef5849C ! #%76CtCFV:<=UX49ZC 7U1-^`_CFT 4658lRUl:<c<:Z@±gef5U4Z9_CYpRU76C _Ct; l£5UZ[_ c<5Yt:MYpRU4646± RUc<c\Ctc\Ct7° RU;d ¥:<7 ! # '1 CDYpRUX76Cv.Cd5;5rZ ;5 Â_:\Yz_~5reZ[_C Yz_4658k587958kCt7.Z[_RrZYpRU4646±:<CD7RUc<c\Ctc\C°§584 C YtRU;;5UZ«79CtC :e l 5UZ9_SYz_4958k58795UkgCD7RU49C49CDYt58kml:<;Rr;Z5U4`l 5UZ9_WRr49C ;58;>@49CDYt58kml:<;Rr;Zt1 \ f 'À /'/pÀ ¾ 1 ¾¿ À¡¾ - ¼ f½ p½S¿ 62XTT£5879C Z9_Ct46CRU49CbZ9_49CDCkvRU46UCD497RUc\58;=¯RuYz_4658k587958kCU21 eZ9_C =8Ct;CDZ[:\YbZ@±T CGRrZ Z[_/C 4676ZkgRU49rCt4:\7X;;5B;.CYtRU;;5rZ Ct7NZ[:<kgRrZ9CFZ[_C¯49CtYD58kul:\;RrZ9:<58;~ef4[RUYnZ[:<5U; :<; Z[_C 497NZ«:\;Z9Ct4NAURrc 1^`_C79RUkgC_58c\d7M:\e Z[_CZ@±T C:<7-kg:\7976:<;=GRrZMZ[_Cc<RU76Z-kgRU49rCt4t1 eZ[_CF=8CD;CDZ9:<YZ@±T£CmRrZZ9_C79CtYD58;dSkvRU46UCD4:\7kg:\7979:\;=u.CFYtRU;S7NZ[:\c<c%CD76Z[:\kvR?Z[CZ[_C 49CtYD58kul:\;RrZ9:<58;ef4[RUYnZ[:\58;F:\;m:\;Z9Ct4NAURrc<F7 «RU;d 021V+5U40C RrkgTc\ C Z[_C.T495UlRUl:\c<:\Z@±Z[_R?Z Z[_C=8CD;CDZ9:<YZ@±T CGRrZc\52YDX,7 GRU;d~c<5YtX7«PRr49C°b°K:\7«Z[_C79Xk 5UeZ[_CT4658lRUl:<c<:Z@± ef584FZ9_Cv58X2Z[Yt5UkgCD17 °b5° °b° x°° °b° x°° `Rr;d °b° x° x°° 1^`_:\7m:\7FZ[_C T4958lRUl:<c\:\Z@±m5Ue_RpA:<;=F°b°#RrZ-Z[_C 497NZ`RU;dgZ[_CZ9_:<46dvkgRU49rCt4t1V+5U4-0C RU kgTc< C Z[_C T4958 lRUl:<c\:\Z@±¯ef584 °5° > ! >M46CtT46Ct79CD; ZbRFkg:\7979:\;=mArRUc\X)C #M:<"7 ! # !' # 0 !' # !' #n1M^`_CT4658lRUl:\c<:Z[:<CD7Rr49C 58lZ[RU:<;Ctds:<;sZ9_C 7[RUkCRB± :\e$Z[_CD49CGRU49Ck5849C kgRU46UCt467`:\Z[_yk5849C k:<7679:\;=uArRUc<XCD7`c<:\UC °b5° > > $° 1 °7 d:<76YtX7679Ctd :<; 62CtYnZ[:<5U;1 u.C 7958kCDZ9:<kCt7;5 Z[_RrZZ[_C¯=8Ct;CnZ[:\YmZ@±T C :<7 Ct:\Z9_Ct4°b°¶5U4$° RU;d¯795UkgCnZ[:<kCt7$:\Z:<7Ct:Z[_CD4 584$° b1?^`_:\7:<7_RU;dc\Ctd¯Rrc<k5876Z :<;SZ9_CG7[RUkCGRp±SRU7_Ct;W.Cm_RpAUCuRgk:<7679:\;=¯AURrc<XCr1«^RrUCmZ9_CF0C RUkgTc<CGRUl£5 AUC ph.

(134) Locus 1, AB. Chromatid M. V:<=8X49C27. . Chromatid P. Locus 2, AA. . '#%& '&'# " !$#% ! '

(135) . ' $( '#%& '&'# !7 '$# #% " !$#% '#%& '&'# !7 '7# #% " !$#%

(136) !

(137) ' ' $ (. . . . :\Z[_SZ[_CF79CXCD;YtC °b° >$x°° Rr;d79XTT 5U79CmZ9_RrZZ[_:\7Z[:\kgC .Cu;5BKZ[_R?ZbZ[_C =8Ct;5rZ@±2T£CRrZZ9_C`79CDYt58;dkgRU49rCt4:\7)Ct:\Z9_Ct4°b°584°b18^`_CD ;¯ Z[_C`c\:<UCDc<:\_525dm:\7Z[_C 79Xk 5Ue °b5° °b° x°° RU;d °b°5°$x°° Z9_RrZM:\7 !' # 0 ! # ! #n1 (ML µ" Locus 1 Interval 1. Interval 4. Locus 1 Interval 1. Interval 4. V :\=8X46CZ 07

(138) *7 # ( V:A8CFc<5Yt:$58;WZ@.5s_58k58c<58=U58X7Yz_4958k587658kgCD7 RU46Cm58l76Ct4NA8Ctd :<;0r4[R?Z[7t1b^`_C 58l79CD46AUCtd¢=UCt;5UZ@±T£Ct7RU46CT49CD79CD;Z9Ctd :<; ^RUlc\C 81 CnZ l CgZ[_CsT4658lRUl:<c<:Z@± 5Ue 49CtYD58kul:\;RrZ9:<58;s:\;~:\; Z[Ct4NArRUc 91M^`_Cc\:<UCDc<:\_525dvef584`49RrZ :<7 !' # 0 !$ #! !' # # !' # 0ro Locus 5. Locus 5.

(139) %' 3407 . . 0 b° ° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b° °b°. P. . . °° ° ° 0 : ° °$ P ° $ °b° °b° °b° °° °b° °b° °° ° ° H : ° °$ ¬ ° $ °b° °b° °b° ] °° °b° °b° h °° ° ° Bo : ° °$ 7 ° $ °b° °b° °b° 0 °° °b° °b° BP °° ° ° p : ° °$ ° $ °b° °b° °b° BH °° °b° °b° ¬ °° ° ° B] : ° °$ Bh ° $ °b° °b° °b° 0Uo °° °b° °b° 0 °° ° ° 080 : ° °$ 0UP $° °b° °b° °b° 0r °° °b° °b° ^RUlc\CA "''# . '( ^`_C c<:<rCtc\:<_552d7ef584Z[_Cu5rZ[_CD4 4[RrZ97RU49CudCDZ[CD49k:<;CDd79:\kg:\c|RU46:<c\±U1b^`_C¯c\:<rCtc<:\_552d ef584`Z[_C _58c\CdRrZzRr79CDZ ! #0:<7`Z[_CT4652dXYDZ5Ue$Z[_CGc<:\UCtc\:<_55d7.ef584`CtRUYz_ 4[RrZt1)^RU:\;=Z9_C;RrZ9X4[RUcc<58= Rr49:\Z9_k5UeZ9_Cc<:\UCtc\:<_55dv=8:A8Ct7`Z9_Cc<58=r> c<:\UCtc\:<_55d c<; ! # hMc\1; !$ # P)c<; ! !$ # # PMc\1 ; ! 0 !' # # h)c<; !' # PMc\1 ; ! P ! # # PM c\1; ! 0 !' # # H)c<; ! !$ # # PMc\1 ; ! !' # # P)c<1; ! ! # # PMc\1 ; ! !' # # P)c<; ! 0 !$ # # . 0&. . .

(140) ^5kvR4:\kg:\79CZ[_:\7C02T49CD7979:\58;.CZ[RUUCZ[_CGdCt49:ArRrZ[:A8C .

(141)

(142) ef584`CDAUCt4N± ! # P b! 0 0 # ! 0 # c<; ! # 0 P b0 0 0 ! # ! # c<; ! # 0 0 0 b0 0 !$ # 0 !$ # !$ # c<; ! # 0 0 b0 0 0 !$ # ! # !$ # 0 ! # C;5B ;dvZ[_CArRUc<XCt75re Z9_RrZ«kgRUrCt7.Z9_Ct76CC XR?Z[:<5U;7C XRUc£Z95 tCD4951 @; Z9_:<7m79:<kTc\Cv%C RUkTc\ C RU46C:<;dCtT£Ct;dCD; Z -795.C~YtRU; 795Uc\A8CZ9_Cef58X4 C XRrZ9:<58;7.58;CRrZ.RGZ9:<kCU1^`_CbYt5BArRU46:|RU;YDCt7.RU49C tCD4951)^`_:<7-:<7M;5UZ-Z[_CYpRr79C_Ct; Z[_CD49CFRU49C :\;Yt58kTc\CDZ[Cb584kg:\7979:\;=uArRUc<XCt7t1 6258c\A:\;=¯Z[_CC XR?Z[:<5U;7RUl£5 AUCF=U:\A8CD7`Z[_CCt7NZ[:\kvRrZ9Ctdy49CDYt58kml:<;R?Z[:<5U;vef4[RUYnZ[:\58;7 % o 08 % o 08 % o BjP GRU;d % o 0U]U ^5 =8CDZ Z9_Cy=8Ct;CnZ[:\Y~d:<76Z[RU;YD C .R kgRUT efX;YnZ[:<5U; _RU7¯Z[5 l CyX76Ctd%1 ^`_Cyc<CD;=UZ[_7 ! #5Ue$Z[_Cef5UX4`:<; Z[CD46ArRUc\7`X79:\;=abRUc\dRU;C x7kgRUTsefX;YDZ9:<58;~RU46C % " CBo8o 0 c\1; !' 0 -# RU;dSj5U7[RUkul: 7`kvRUTsefX;YDZ[:\58;y=8:\AUCt7 % BoUo c<; ! 00 # 79CtCF^Rrlc<Cm0gRU;dW^RUlc<CGP ef584;XkgCD49:<YtRUcCt7NZ[:<kgRrZ9Ct7t1^`_Cmd:\76Z[RU;YtCG:<7kuXc\Z[:\Tc<:\Ctd l)± po8oZ[5=8CDZMZ9_CX;:\ZMYDCt; Z[:|QS5846= RU;%1^`_CYD5 ArRU46:|RU;YtC`kgRrZ[46: m:<7MCt7NZ[:<kgRrZ9Ctd¯:\Z9_ Z[_C:<;2ef5849kgRrZ[:\58;kgRrZ[46: 76Ct5C 62CtYnZ[:\58;~P1x 1 @;yZ[_:<7`%C RUkTc\CZ[_CYt5BArRU46:|RU;YDCt7RU46C tCt465 l CDYpRUX76C RU49Cv:<;dCDT CD;dCD;Zt1 ^`_Cs:\;ef5846kvRrZ9:<58; kgRrZ[46: 58;c± _RBAUC ;58;2> tCt465sCtc\CtkCt; Z[7 58;SZ[_C¯d:<RU=858;RUc +795Z9_C¯:<; AUCt4976C¯:<758lZzRr:<;CDdl±SZzRU:\;=vZ[_C :<; A8CD49Ct76Cg5re.Z9_C d:|RU=U58;RUc$Ctc\CtkCt; Z[7D1¯^`_C d:|RU=U58;RUcCtc<CDkgCD; Z[7 :<;Z9_C¯Yt5BArRU49:<RU;YDC . +. &. . . 0U0.

(143) kvRrZ949: l£Ctc\5 RU49CZ9_C ArRU49:<RU;YtC 5reZ[_CG46CtYD58kul:\;RrZ[:\58;vef49RUYDZ9:<58;%1 o o o o o o o o o o o o . @;79CD46Z[:\;=Z[_C Q >@Ct7NZ[:\kvRrZ9Ct7:<;mZ9_C`Yt5BArRU49:<RU;YDCkgRrZ[46: F=8:\AUCt7Z9_C`Ct7NZ[:\kvRrZ9CtdmArRU46:> RU;YtCD7 % o o8o 0808¬rh % o o8o 080U¬Uh % o o8o80UjH 0¯RU; d % o o8o8 Uh UH ^`_:<7-RU46C«Z[_C«ArRU46:|RU;YDCt7)5Ue£Z[_C`49CtYD58kul:\;RrZ9:<58;uef49RUYDZ9:<58;7D1^$5=8CDZ)Z9_CÀURr49:|Rr;YtCD7)5Ue Z[_C=8Ct;CDZ[:\Yd:<76Z[RU;YDCt7 !¡76CtC 62CtYnZ[:<5U;vP1xP #0.CbX79C.q XR?Z[:<5U;7HFRU;dv¬FRU;dg58l2ZzRU:\; . . . .

(144) . . . . . . . . . . . .

(145)

(146) . . . % " 4 . !' 0 % # . % 54 . . !' % # . ½ , ½7/ À¡¾21 ¿À/ ¾8½$/ gÀ / ¾$¿ ,r¿¿½6À À - ¾2/ @;Z9Ct4NAURrc CDYt58kml:<;R?Z[:<5U;yV+49RUYDZ9:<58; QWRUT~d:<7NZp1! aRUc<dRU;C)# 6Zt1)dCDA£1 ! abRrc<dRU;C)# o1 B08 t1xUYBQ H 18YBQ 0 o1 B08 t1xUYBQ H 18YBQ P o1 pjP B 21 tYBQ H 1xhUYBQ o10r]U 021iorYBQ 2¬ 1xhUYpQ ^5UZ[RUc ]8 21iHrYBQ 2¬ 1xhUYpQ ^RUlc\Cm0$ ""$ ! ' (. . . . . . 0rP. . . .

(147) @;Z9Ct4NAURrc. 0. . P ^ 5UZ[RUc . CDYt58kml:<;R?Z[:<5U;ef4[RUYnZ[:<5U; QWRUT~d:<7NZzRU;YtC ! j 5879RUkul: # 6Zp1MdCDA£1! j 5879RUkul: # o]1 08 01i]UYpQ 21]pYpQ o]1 08 01i]UYpQ 21]pYpQ o]1 BjP BP21x8YpQ 21i rYpQ o1i0U]U P 010rYpQ 7818YpQ ¬ U1 pYpQ p1xHUYpQ ^RUlc\CP *""7 ! & ' ' ( . . . 0?. . . .

(148) S 6(". (% ¡¶£.¤-.¤" ¥&m"§¦¨ ^`_CudRrZ[RvYt5U;Z[RU:<;7hvkgRU49rCt467RU;d UHU58l79Ct4NA8CDd 49RrZ[7D1 R?ZzRef4658k hv4[R?Z[7b_RBAUC l CDCt; %C 2Ytc\XdCtd l£CtYtRUX79Cy5UeZ9_Cs_:<=U_ ;Xkul CD4¯5Ue tCD49587 !fkg:\7979:\;=WArRUc\XCt7$#n1 ^`_C ;RUkC5UeZ[_CskgRU46UCt467 RU49Cvc<:<7NZ[CDd :<; ^RUlc\C_Ct46Cs7958kCs5Ue`Z9_Cs58l76Ct46ArRrZ9:<58;7 RU49C T46Ct79CD; Z[Ctd1 &5~CD76Z9:<kgRrZ[:\58;7YtRU; l£C kvRrdC¯58; BP8hs5Ue-Z[_C¯49RrZ[7l£CtYtRUX79C Z[_C 58l79CD46ArRrZ9:<58;7 5U;c\±SYt58; Z[RU:<;:\;ef5849kgRrZ9:<58;SRrZZ9_/C 497NZkvRr49UCD4 !¡58l79Ct4NArRrZ[:\58;7080U¬ Z[5 P8H :<; ^RUlc<C #n1^`_Ct46C Rr49C RUc<765 Bh8o 4[RrZ97_Ct46C Z9_C dRrZzR RrZsZ9_,C 497NZ Z[_46CtCkgRU49rCt467«RU46Cbk:<7976:<;= !¡5Ul79CD46ArRrZ[:\58;7.P8H8HZ[5 8 U G:<;g^Rrlc<C #n1^`_C5846dCt4.5Ue Z[_CukgRU46UCt467RU46CmdCnZ[CD49k:<;CDdl ±SZ9_CmYD58kgTXZ[CD4bTRUYz?RU=UC QWRUT+QSRUUCD4 RU;dW_Ct; Ct76Z9:<kgRrZ[:\;=vZ9_C¯AURr49:|Rr;YtC %Z[_C¯5846dCt4 dCDZ[CD49k:<;CDd l± QWRUT+QWRrUCt4G:<7RU7976XkgCDd Rr7 Z[_CYt584649CtYnZ«58;CU1)°bc\cYpRUc\YtXc<RrZ[:\58;7)_RpAUCl CDCt;d58;Cb:\;QSRUTc<5C !¡76CtC°bTT£Ct;d: #n1 ^`_CGef5Uc<c<5B:\;=uYt5dCD7Rr49CX79CDd >.a5Ukg5 n±=85UZ[Cef5U4RUc<c\Ctc<Cb° 0F>.a5Ukg5 n±=85UZ[Cef5U4RUc<c\Ctc<$C Pm>.aCnZ[CD495 n±2=U5UZ[C £YtRU494N±:<;= l£5UZ[_~RUc\c<Ctc\Cb°RU;d u> &5rZ_58k5 D±=85UZ9C ef584RUc<c\Ctc\$C : 1xCr1)Ct:\Z9_Ct4`°°'584`$° F> &5rZ_58k5 D±=85UZ9C ef584RUc<c\Ctc\Cb5° : 1xCr1)Ct:Z[_CD4 Â5U4`$° om>QS:\7979:\;= dRrZ[R c<5YtX7 W4[RrZ 0 111 080UH 0U08¬ 1\11 PUH P8H8H 11\1 8 8 0Uo8Rr Z P 111 P P 1\11 P o 11\1 o 0Uo Q~=8_ P 111 P o 1\11 o o 11\1 o 0Uo Q~=8_+¬ o o 111 P o 1\11 o o 11\1 o 6 UP8 ¬ 6P o o 111 P o 1\11 o 0 11\1 0Uo Q~:\Z¹ P 111 o 1\11 o 0 11\1 0Uo8RrZz0UP o o 111 o 1\11 o o 11\1 o 0Uo Q~:\Z[ P 111 o 1\11 o 0 11\1 o 0Uo8RrZz 8 P 111 P o 1\11 o 0 11\1 P 0Uo8RrZz0Uh P 111 P o 1\11 o 0 11\1 P ^RUlc\CG "''# . '( &. . . . . . . . © )6 / À À - ¾ -

(149) $½ 1+½2¾½ À ¼¿À/ ¾8½ * ^5;dZ9_C¯c<:\UCDc<:<_525dS5re)Z[_C¯dR?ZzRdCD79Yt46:<l£Ctd :<;SZ[_C¯T46CDA:<5UX779CDYDZ9:<58;.C/497NZ kvRUdCgRyT4658=84[Rrk :<; QWR?Z[c|Rrl Z9_RrZGYt5UX; Z[7G_5B kvRr;±5Ue.Z9_C d: Ct46Ct; ZFYt58kul:<;2> RrZ[:\58;75Ue=8Ct;5UZ@±T CD7vZ[_CD49CRr49CWl£CDZ@.CtCD;Z[_CSkvRU46UCD497,!f79CtCW°bTT£Ct;d: °*#¹1.^$5 Ct76Z9:<kgRrZ[CZ9_C 46CtYD58kul:\;RrZ[:\58;ef4[RUYnZ[:\58;Z[_C c<:\UCtc\:<_55d¶5UemZ9_C dRrZzR _RU7yZ[5 l£C ef58X;d%1m^`_C c<:<rCtc\:<_552dS:<7 dCnZ[CD49k:<;CDd Rr7 dCt76Yt49:\l CDd :\; 3_RUTZ9Ct41 @; ^RUlc\C Z[_CGc<:\UCtc\:<_55d7.ef584`d: Ct49CD; Zb76C XCt;YtCt7RU49Cc<:\76Z9Ctd Z9_C;RUkCt75UeZ[_C79C XCt;YDCt7 0U .

(150) UR 49C X76CtdS:<;Z[_C C%2T49CD7976:<58;~ef584Z[_C c<:<rCtc\:<_552d+!¡76CtCGq XRrZ[:\58;~ ¬ #n1)^`_CG;Xkml CD4 5UeCtRUYz_W76CXCD;YtCF:<7`49CDT49CD79CD;Z9:<;=:\Z9_SR l£CDef5U49CZ[_CG;RUkgC 5reZ[_CG76CXCD;YtCr1 62C XCD;YtCD7 ;RUkgC :<rCtc<:\_552 d 0 &0 V7 ! # !' # &0 0 V 0 ! # P 0 P VBP ! # 0 !$ # P P &0 Pj ! # !$ # P P P8P ! # !$ # o x0 o &0 VBo V77 V 0 VBP o &0 x0 o VBo80 V7 0 V 080 VBP80 o P x0 o P VBoUP V7BP V 0UP VBPUP P o P o &0 P8o Pj7 P 0 P8P P o P P8oUP PjBP P 0UP P8PUP x0 &0 Vpj U7 VBjP x0 &0 V & B0 VBjP &0 x0 Vp 0 U 0 VBP 0 &0 x0 V U0 B080 VBP 0 P x0 P Vp8P UBP VBP8P P x0 P V rP B0UP VBP8P P P &0 PUj P7 P8jP P P &0 P & P80 P8jP P P P P PU8P PBP P8P8P ^RUlc<C7

(151) ! '#% ' 4 "

(152) &" "

(153) # . . . . . . . . ' "''#. #%

No results found