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72 ;C9/0@3059/ G79@623C0@7@# G-3 73 4/@9 .4537;7.430@ 72 3C0 .59>-;L
3792 98 4 =7>0 D457036 98 93C05 ;91.9-2>@(A ,910 ;/727;4/ G020S3@
43357G-30> 39 72C7G7395@ 98 JOPLQ9: 50>-;34@0 450 29= 3C9-?C3
39 G0 72>0.02>023 98 426 @05-1 ;C9/0@3059/L/9=0572? 0880;3)#$A
J050 =0 >0@;57G0 4 20= ;C9/0@3059/L72>0.02>023 59/0 895 JOPL
Q9: 50>-;34@0# 72 50?-/4372? 4 >0D0/9.10234/ .59;0@@T .57195>74/
?051 ;0// 17?543792A U0 @C9= 3C43 72 +$),)-('"% 3C7@ 02M610 7@
C7?C/6 0F.50@@0> 72 3C0 @91437; ?924> 42> 3C43 73 7@ 20;0@@456 895
.57195>74/ ?051 ;0//@ 39 17?5430 39 3C7@ 37@@-0A [email protected]@@792 98
JOPLQ9: 50>-;34@0 7@ @-8S;7023 39 43354;3 .57195>74/ ?051 ;0//@
39 37@@-0@ 93C05 3C42 3C0 ?924>4/ 10@9>051A U0 ;92;/->0 3C43 3C0
50?-/430> 0F.50@@792 98 JOPLQ9: 50>-;34@0 C4@ 4 ;5737;4/ >0D0/L
9.10234/ 8-2;3792 72 .59D7>72? @.4374/ 72895143792 39 ?-7>0
17?54372? .57195>74/ ?051 ;0//@A
W6 >76D 76@>7BEC @6<B9G@6O >7>>7BE 76G B"#@#56-)'C I:@>=:G@7B
O;:> <;BBE LUc/EM A=:> @6 7 :;O@=6 =A 8F; ;>Q:D= E;I7:78; A:=> 8F;
E=>78@< I=:8@=6 =A 8F; O=67G5 /=6E;g9;68BDC Uc/E >@O:78; 8F:=9OF
8F; ;>Q:D= 76G >7T; EI;<@b< <=687<8E 4@8F E=>78@< <;BBE 8= A=:>
8F; O=67GJC?5 W6 7 O;6;8@< E<:;;6 A=: >9878@=6E 8F78 G@E:9I8 8F@E
I:=<;EE @6 B"#@#56-)'C 4; @G;68@b;G 2? 7BB;B;E =A 7 O;6; 8F78 4; <7BB;G
$#)07D0@ L$)DM-5 _; F7H; <B=6;G $)D 76G b6G 8F78 @8 ;6<=G;E 7
B"#@#56-)' F=>=B=O9; =A S0c[/=" :;G9<87E;R L674$"M5 #4;BH;
;8FDB >;8F76; E9BIF=678; L&0ZM[@6G9<;G 7BB;B;E 76G =6; 8:76EI=[
E=6[@6G9<;G 7BB;B; =A $)D 4;:; ;P7>@6;G 76G 7BB EF=4 >=B;<9B7:
G;A;<8E @6 8F; 674$" 8:76E<:@I8 LX@O5 2C 76G G787 6=8 EF=46MV 4;
Nonsense alleles
Catalytic domain
Missense alleles
-$./+* 0 >#(0+30$ #- !"#$#%&'() UI`7Q&H "(.0$+*-(4 !%( UI`7Q&H "(.0$+*-(
&)(, "(*.#,3 /"*'( #- -%&F, -$%('*+#$*;;24 !%( $&,-("1(. *'#,& +("'#,092(;;&F F#+% +"*,-'('A"*,( .&'*#,- #, "(.@ *,. +%( $&,-("1(. $*"A&G27
+("'#,*; $*+*;2+#$ .&'*#, 9A;0(@ *"( L?_ *,. ?C_ #.(,+#$*; +& %0'*, UI`7Q&H
"(.0$+*-(5 "(-)($+#1(;24 I0+*+#&,- /&0,. #, >> VIa7#,.0$(. *;;(;(- *"( #,.#$*+(.
A2 *""&F- 9,&,-(,-( *;;(;(- *A&1( *,. '#--(,-( *;;(;(- A(;&F +%( &)(, "(*.#,3
/"*'(@4 6,( VIa7#,.0$(. *;;(;( %*- '0+*+#&,- #, A&+% * $&,-("1(. *'#,& *$#. #,
+%( $*+*;2+#$ .&'*#, *,. +%( +"*,-'('A"*,( .&'*#, *,. #- ,&+ "()"(-(,+(. #,
+%( W30"(4
Nature © Macmillan Publishers Ltd 1998
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