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phwhu zklfk duh vljqlfdqwo| pruh dffxudwh wkdq wkh irupxodh rewdlqhg
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vwuxfwxuhv +vhh Iljxuh 6, e| xvlqj wkh krprjhql}dwlrq phwkrg dqg glvfuhwh qhw0
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glvfuhwh qhwzrun dqdo|vhv1 Vrph ri wkhvh irupxodh fdq dovr eh rewdlqhg iurp
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ehdp0qhwzrunv1 Iru wkh frqyhqlhqfh ri wkh uhdghu zh suhvhqw wkh ghwdlohg surriv1
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phwkrg/ zh revhuyh lq Vhfwlrq 6 wkdw wkh xvxdoo| vpdoohvw hhfwlyh wudqvyhuvh
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irupxodh rewdlqhg iurp glvfuhwh qhwzrun dqdo|vhv1
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lq0sodqh, exon prgxoxv N  / dqg wkh hhfwlyh wudqvyhuvh vkhdu prgxol JW >
dqg JW>78 / +vhh Iljxuh 4, e| xvlqj glvfuhwh qhwzrun dqdo|vhv +vhh ^9`,/ dvvxplqj
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3=<<365984
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Glvfuhwh qhwzrun dqdo|vlv +GQD, dvvxphv wkdw wkh vwuxfwxuh frqvlvwv ri lqqlwho|
orqj dqg wklq ehdpv ru sodwhv/ zklfk phdqv wkdw zh pdnh xvh ri wkh hohphqwdu|
wkhru| ri ehqglqj1 Lq wkh fdvhv zh frqvlghu/ wklv wxuqv rxw qrw wr eh d jrrg
dvvxpswlrq1 Wklv jlyhv ulvh wr dq huuru lq wkh irupxod ghulyhg iurp GQD1
Iljxuh : vkrzv wkdw irupxod +48, lv pxfk pruh dffxudwh wkdq wkh irupxodh
rewdlqhg zkhq zh xvh GQD +iru yroxph iudfwlrqv yL A 3=7> l1h1 uhodwlyh wklfnqhvv
w@o ? 3=6:/ wkh dffxudf| ri +48, lv hyhq ehwwhu wkdq 4=;(,1 Lq dgglwlrq zh qrwh
wkdw wklv lpsuryhg irupxod +48, lv mxvw dv vlpsoh dv +<, dqg +43,1

43

Wdeoh 5/ Ydoxhv ri htxdwlrqv +<,/+43,/ dqg +48,


Fodvvlfdo
sodwh wkhru|

+ehqglqj.vkhdu,

yL
3=<
3=;
3=:
3=9
3=8
3=7
3=6
3=5
3=4

Htxdwlrq +<,
 @ 4> n @ 4
8=8
+plq= 7= 9,
47= 4
+plq= 43= 9,
58=3
+plq= 4;= 3,
69=<
+plq= 59=:,
7;=9
+plq= 69=6,
8<=4
+plq= 79=8,
9:= 8
+plq= 89= <,
:6= 8
+plq= 9:=3,
:9=9
+plq= :9=3,

pg J
W>78 ^(`
Fodvvlfdo
sodwh wkhru|

+sxuh ehqglqj,

Htxdwlrq +43,
 @ 4> n @ 3
7=53
+plq= 7=4:,
<= 3;
+plq= ;= <5,
47= 99
+plq= 47= 3;,
53= <6
+plq= 4<= 75,
5:= ;8
+plq= 57= 89,
68= 6:
+plq= 5;= ;:,
76= 68
+plq= 64= 5:,
84= 78
+plq= 5<= 73,
8;= :5
+plq= 49= <<,



ph J 
W>78
Lpsuryhg
irupxod
Htxdwlrq +48,
 @ 4>  @ 4
3=<:<
+plq=  3= <;7,
4= 8:<
+plq=  4= 8;8,
4= :59
+plq=  4=:65,
4= 636
+plq=  4=649,
3= 544
+plq=  3=54<,
4=:93
+plq= 4= 8;;,
7=;46
+plq= 6= <<6,
<=389
+plq= 9= 739,
47=369
+plq= := 83:,

3=347;
3=3537
3=356<
3=3658
3=37;7
3=3745
3=36;7
3=349:
3=34<3
Wdeoh 5

Uhihuhqfhv
^4` Ednkydory Q1 V1 dqg Sdqdvhqnr J1S1/ +4<;<,/ Krprjhql}dwlrq= Dyhudjlqj
Surfhvvhv lq Shulrglf Phgld/ Noxzhu +Gruguhfkw,1

^5` Ehujjuhq V1 D1/ Oxnndvvhq G1/ Phlghoo D1 dqg Vlpxod O1/ Vrph phwkrgv iru
fdofxodwlqj vwlqhvv surshuwlhv ri shulrglf vwuxfwxuhv1 Dssolfdwlrq ri Pdwk1 +wr
dsshdu,1

^6` Ehujjuhq V1 D1/ Oxnndvvhq G1/ Phlghoo D1 dqg Vlpxod O1/ Rq vwlqhvv surshuwlhv

ri vtxduh krqh|frpev dqg rwkhu xqlgluhfwlrqdo frpsrvlwhv1 Frpsrvlwhv Sduw E1


+wr dsshdu,1

^7` Fkhfknlq J1 D1/ Mlnry Y1 Y/ Oxnndvvhq G1 dqg D1 O1 Sldwqlwvnl/ Rq krprjhql}d0


wlrq ri qhwzrunv dqg mxqfwlrqv/ Wr dsshdu lq= Dv|pswrwlf Dqdo1

44

^8` Flrudqhvfx G1 dqg Sdxolq M1 V1 M1/ +4<<;,/ Krprjhql}dwlrq ri Uhwlfxodwhg Vwuxf0

wxuhv/ Dssolhg Pdwkhpdwlfdo Vflhqfh +hg1 Pduvghq M1 H1 dqg Vlurylfk O1,/ 469/
Vsulqjhu/ Qhz \run1

^9` Jlevrq O1 M1/ dqg Dvke| P1 I/ +4<<:,/ Fhooxodu vrolgv/ Vhfrqg hglwlrq/ Fdpeulgjh
Xqlyhuvlw| Suhvv/ Fdpeulgjh1

^:` Juhhqjdug O1 dqg Khovlqj M1/ +4<<;,/ Rq wkh qxphulfdo hydoxdwlrq ri hodvwrvwdwlf

hogv lq orfdoo| lvrwurslf wzr0glphqvlrqdo frpsrvlwhv/ M1 Phfk1 Sk|v1 Vrolgv/ 79/


4774047951

^;` Kdvklq ]1/ +4<;6,/ Dqdo|vlv ri Frpsrvlwh Pdwhuldov 0 D Vxuyh|/ M1 ri Dssolhg


Phfkdqlfv/ 83/ 7;408381

^<` Khovlqj M1 dqg Mrqvvrq D1/ +4<<<,/ Hodvwrvwdwlfv iru sodwhv zlwk krohv/ Ghsduwphqw
ri Vrolg Phfkdqlfv/ NWK Uhvhdufk Uhsruw WULWD0KOI035831

^43` Kroperp D1/ Shuvvrq/ O1 H1 dqg Vydqvwhgw Q1/ +4<<5,/ D krprjhql}dwlrq surfh0

gxuh iru frpsxwlqj hhfwlyh prgxol dqg plfurvwuhvvhv lq frpsrvlwh pdwhuldov1 M1


Frpsrvlwh Hqjlqhhulqj 5/ Qr 7/ 57<058<1

^44` Mlnry Y1Y1/ Nr}ory V1P1 dqg Rohlqln R1D1/ +4<<7,/ Krprjhql}dwlrq ri glhuhqwldo
rshudwruv dqg lqwhjudo ixqfwlrqdov/ Vsulqjhu0Yhuodj/ Ehuolq1

^45` Oxnndvvhq G1/ +4<<<,/ D qhz uhlwhudwhg vwuxfwxuh zlwk rswlpdo pdfurvfrslf eh0
kdylru/ VLDP M1 Dsso1 Pdwk1 8</ 8/ 4;5804;751

^46` Oxnndvvhq G1/ Shuvvrq O1 H1 dqg Zdoo S1/ +4<<8,/ Vrph hqjlqhhulqj dqg pdwk0

hpdwlfdo dvshfwv rq wkh krprjhql}dwlrq phwkrg1 Frpsrvlwhv Hqjlqhhulqj 8/ 8/


84<08641

^47` Phlghoo/ D1 dqg Zdoo/ S1/ +4<<:,/ Krprjhql}dwlrq dqg ghvljq ri vwuxfwxuhv zlwk rs0

wlpdo pdfurvfrslf ehkdylru/ lq Khuqqgh} V1 dqg Euhggld F1D1 +hgv1,/ Frpsxwhu


dlghg rswlpxp ghvljq ri vwuxfwxuhv Y/ Frpsxwdwlrqdo Phfkdqlfv Sxeolfdwlrqv/
Vrxwkdpswrq/ 6<607351

^48` Phlghoo/ D1/ +4<<;,/ Wkh rxw0ri0sodqh vkhdu prgxoxv ri wzr0frpsrqhqw uhjxodu
krqh|frpev zlwk duelwudu| wklfnqhvv/ lq Phfkdqlfv ri Frpsrvlwh Pdwhuldov dqg
Vwuxfwxuhv +hgv1 F1D1 Prwd Vrduhv/ F1P1 Prwd Vrduhv dqg P1M1P1 Iuhlwdv,/ QDWR
DVL/ Wurld/ Sruwxjdo/ Yro1 LLL/ 69:06:<1

^49` Phlghoo D1 dqg Shuvvrq O1 H1/ +4<<<,/ Rswlpdo ghvljq ri uhfwdqjxodu krqh|frpev lq
uhfwdqjxodu vdqgzlfk sodwhv/ Surfhhglqjv ri 9 Lqwhuqdwlrqdo Frqihuhqfh rq Frp0
srvlwhv Hqjlqhhulqj/ 89:089;/ Ruodqgr1

^4:` Sdqdvhqnr J1S1/ +4<<5,/ Dv|pswrwlf vroxwlrqv ri wkh hodvwlvlw| wkhru| v|vwhp ri

htxdwlrqv iru odwwlfh dqg vnhohwdo vwuxfwxuhv/ Pdwk1 Veruqln/ 4;6/ 4/ ;<0446 +lq
Uxvvldq,1 Hqjolvk wudqvodwlrq= +4<<6,/ Dfdg1 Vfl1 Veruqln Pdwk1/ :8/ 4/ ;804431

^4;` Shuvvrq O1H1/ Shuvvrq O1/ Vydqvwhgw Q1 dqg Z|oohu M1/ +4<<6,/ Wkh krprjhql}dwlrq
phwkrg= Dq lqwurgxfwlrq/ Vwxghqwolwwhudwxu/ Oxqg1

45

^4<` Wlprvkhqnr V1 S1 dqg Jrrglhu M1 Q1/ +4<84,/ Wkhru| ri hodvwlvlw|/ Wklug Hglwlrq
+4<;:,/ PfJudz0Kloo/ Lqf1/ Qhz \run1

^53` Wrutxdwr V1/ Jleldqvnl O1Y1/ dqg Jlevrq O1 M1/ +4<<;,/ Hhfwlyh Phfkdqlfdo dqg
Wudqvsruw Surshuwlhv ri fhooxodu Vrolgv/ Phfkdqlfdo Vflhqfhv/ 73/ :40;51

^54` ]lhqnlhzlf} R1 F1 dqg ]kx M1 ]1/ +4<;:,/ D vlpsoh huuru hvwlpdwru dqg dgdswlyh
surfhgxuh iru sudfwlfdo hqjlqhhulqj dqdo|vlv/ Lqw1 M1 iru Qxphulfdo Phwkrgv lq
Hqjlqhhulqj/ Yro1 57/ 66:068:1

46

Dsshqgl{ D
Wkh lqhtxdolwlhv +46, duh suryhg dv iroorzv= E| xvlqj wkh lqhtxdolw| md . em 
mdm  mem zh jhw


 
 . J  J 
  J

J
J
J
W>78
Irup
W>78
W>78
Irup
W>78
@ 433

pg J
W>78 @ 433

J
J
W>78
W>78

 433



 
J

 
W>78  JIrup
J
W>78

 433



 

JW>78  JW>78 


J
W>78

 

 
JW>78  JW>78 
W>78  JIrup
 433
433
JW>78
J
W>78
 


J

W>78  JIrup
 ph JW>78 >
433
JW>78
 
J




zklfk jlyhv wkh uljkw vlgh ri +46,1 Vlploduo|/ e| xvlqj wkh lqhtxdolw| md . em 
mdm . mem zh rewdlq


 
 

J
JW>78  JIrup . J
W>78
W>78

pg J
W>78 @ 433

JW>78


 
 

Irup 
J
 JW>78 
J

J
W>
78
W>78
. 433

 433
J
J
W>78
W>78
 
 
J
W>78  JIrup
. ph JW>78 >
 433
JW>78
zklfk jlyhv wkh ohiw vlgh ri +46,1

Dsshqgl{ E
Wkh qxphulfdo ydoxhv duh suhvhqwhg khuh1

47


3=<8
3=<
3=;
3=:
3=9
3=8
3=7
3=6
3=5
3=4
3
3=4
3=5
3=6
3=7
3=78

3=<8
3=<
3=;
3=:
3=9
3=8
3=7
3=6
3=5
3=4
3
3=4
3=5
3=6
3=7
3=78

yL @ 3=4
J
W>78 @H
6=<:4:984343
5=34:3947963
4=37454<:563
3=:4:73388:3
3=889:353796
3=79468633:4
3=6<;::<:464
3=688367;866
3=656488::5<
3=5<<5<854;7
3=5;44869698
3=59:5<6639;
3=589::37393
3=57;<943646
3=57677649:
3=574786<653

ph JW>78 ^(
3=34<3
3=34;;
3=34;6
3=34:;
3=34:5
3=349:
3=3494
3=3488
3=347<
3=3476
3=3469
3=3463
3=3456
3=3449
3=3443
3=343;

yL @ 3=5
J
@H
W>78
4=:;75787693
<=4465376;33  434
7=:9484;4533  434
6=656;547853  434
5=9493953833  434
5=5349867583  434
4=<686473873  434
4=:883;76<:3  434
4=9635;:9783  434
4=87758;9643  434
4=7;:797<;:3  434
4=78773<9833  434
4=7754:43:<3  434
4=77<:565<63  434
4=7::9<88;73  434
4=8333556683  434

yL @ 3=6
J
@H
ph JW>78 ^(`
W>78

;=6:7896833  434
7=5;;333683  434
5=585699843  434
4=8;48535:7  434
4=585;69468  434
4=394<;7<5:  434
<=74389;883  435
;=944;43963  435
;=3;5363443  435
:=:78<<8<33  435
:=896356653  435
:=8463:<543  435
:=8<3<968:3  435
:=;37;5;893  435
;=4:;8:55;3  435
;=76;:57983  435

3=36;7
3=36;5
3=36:<
3=36:8
3=36:5
3=369;
3=3698
3=3694
3=368;
3=3687
3=3684
3=367<
3=367:
3=367:
3=3684
3=3688

48

ph JW>78 ^(`
3=349:
3=3499
3=3497
3=3495
3=3493
3=348:
3=3488
3=3485
3=3483
3=347:
3=3478
3=3475
3=346<
3=346:
3=3469
3=3469

yL @ 3=7
J
@H
ph JW>78 ^(`
W>78

6=<6<75;783  434
5=34<76:9:5  434
4=396759;<:  434
:=7;:::5443  435
8=<83393;43  435
8=3945;<853  435
7=8359<8:<3  435
7=46<43<5:3  435
6=<37966;;3  435
6=:97;;4963  435
6=:3544:<83  435
6=:3;<76883  435
6=:;94:76;3  435
6=<75<8<5:3  435
7=4<<9<3:<3  435
7=6:9988333  435

3=369;
3=369;
3=3699
3=3697
3=3696
3=3695
3=3694
3=3693
3=3693
3=3694
3=3696
3=3699
3=36:4
3=36;4
3=36<:
3=3745


3=<8
3=<
3=;
3=:
3=9
3=8
3=7
3=6
3=5
3=4
3
3=4
3=5
3=6
3=7
3=78

3=<8
3=<
3=;
3=:
3=9
3=8
3=7
3=6
3=5
3=4
3
3=4
3=5
3=6
3=7
3=78

yL @ 3=8
J
@H
W>78
4=:;8;97733  434
<=48<<:;963  435
7=;5<7;;483  435
6=738489983  435
5=:43336:43  435
5=63<4:5<:3  435
5=38;684<<6  435
4=;<96<:67:  435
4=:<6973;54  435
4=:67:7673:  435
4=:4535;676  435
4=:55:7756<  435
4=:9;4:83<3  435
4=;87385<98  435
4=<<5835688  435
5=3;;3:3743  435

ph JW>78 ^(`
3=379:
3=3798
3=3795
3=378<
3=3789
3=3786
3=3784
3=377<
3=377:
3=3778
3=3778
3=3779
3=377;
3=3788
3=379<
3=37;7

yL @ 3=:
J
@H
ph JW>78 ^(`
W>78

5=94;9:3;9;  435
4=676:33778  435
:=3<3989683  436
8=33765:7;3  436
6=<;:38:7;7  436
6=7348833:;  436
6=369685<3;  436
5=;34<;93;;  436
5=98848<5:5  436
5=8:69<:5;<  436
5=879:95596  436
5=8:43476;8  436
5=97<7:4;;4  436
5=:<57<3376  436
6=35484:695  436
6=4;33<;76<  436

3=3558
3=3557
3=3556
3=3555
3=3554
3=3553
3=3553
3=354<
3=354<
3=354<
3=354<
3=3553
3=3555
3=3559
3=3566
3=356<

49

yL @ 3=9
J
@H
W>78
:=759<:6763  435
6=;437834;3  435
5=3435395<4  435
4=74;5<:663  435
4=45<8<;:86  435
<=9666;6:33  436
;=8<8599<33  436
:=<5::88673  436
:=83:;79993  436
:=5:566<;43  436
:=4<34766;3  436
:=58444;8:3  436
:=795:8<493  436
:=;8593:7:3  436
;=7::<<9;53  436
;=<437;;683  436

ph JW>78 ^(`
3=363;
3=363:
3=3638
3=3637
3=3635
3=3634
3=35<<
3=35<;
3=35<:
3=35<:
3=35<:
3=35<;
3=3633
3=3638
3=3647
3=3658

yL @ 3=;
J
@H
ph JW>78 ^(`
W>78

9=96:44<363  436
6=738;687<7  436
4=:<:77;794  436
4=59;:5<7:8  436
4=343<9::<5  436
;=959765483  437
:=:3499<843  437
:=43;9;;:73  437
9=:6:;7;583  437
9=865<<9<;3  437
9=799;:;733  437
9=864544:;3  437
9=:67384:53  437
:=435678343  437
:=9<4:8;9;3  437
;=433337363  437

3=34:5
3=34:5
3=34:4
3=34:4
3=34:3
3=34:3
3=34:3
3=34:3
3=34:4
3=34:5
3=34:6
3=34:9
3=34:<
3=34;8
3=34<8
3=3537


3=<8
3=<
3=;
3=:
3=9
3=8
3=7
3=6
3=5
3=4
3
3=4
3=5
3=6
3=7
3=78

yL @ 3=<
J
@H
W>78
:= 5669;776<  437
6= :45344866  437
4= <8<439438  437
4= 6;5;;<<83  437
4= 434<;4<83  437
<=7367<7743  438
;=6<8<47;93  438
:=:7<<<3859  438
:=67958879;  438
:=456869739  438
:=3854:8:;9  438
:=4565:59:9  438
:=678:35558  438
:=:7<385<43  438
;=6<77898:3  438
;=;748;:753  438

ph JW>78 ^(`
3=3454
3=3454
3=3453
3=3453
3=3453
3=3453
3=3453
3=3453
3=3453
3=3454
3=3456
3=3458
3=345;
3=3466
3=3474
3=347;

Zh kdyh xvhg txdgulodwhudo hohphqwv zlwk hljkw qrghv wkdw ghqh wkh hoh0
phqw1 Hdfk qrgh kdv wzr ghjuhhv ri iuhhgrp> wudqvodwlrqv lq wkh qrgdo {4 dqg
{5 gluhfwlrqv1 Lq wkh wdeoh ehorz zh kdyh olvwhg wkh vshflf qxpehu ri hoh0
phqwv dqg qrghv xvhg iru hdfk yroxphiudfwlrq zkhq vroylqj wkh qlwh hohphqw
sureohpv1 Wkh vdph hohphqwphvk lv xvhg iru hdfk Srlvvrq*v udwlr zlwklq hdfk
yroxphiudfwlrq1
yL
3=4
3=5
3=6
3=7
3=8
3=9
3=:
3=;
3=<

Qxpehu ri
hohphqwv qrghv
;798
58<5;
;;44
5<<8;
:<<8
5778:
;;<:
5:495
<975
5<754
94;5
4<344
:696
55975
:836
56463
97;3
5344<

4:

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