10
qq 10 \llq; 2 2002 165-174 '< fit Cf) I o:a \ifq >11 Ell fi'lchl 'l1ffifm mm-r: -.:rACf qRlll \Jl1 I ct 1:Tcf -q WT'l11T m -.:rACf 3K<.R1 'iU3«1'"Fl :rem \3\JfTlR -q ct 1@j3lT cnr 3rmT fuJm 11m qRlll\Jl"11 ct m -.:rACf ct xtq$1, f.'rcrRur, >f\iA"1", flliilf"G1Cl'l fcrCl'lRr ct m -q \Jl1"1Cl'lI{l -.:rACf ct 23 (22 + XX or XY) ¢f>llildlii'j ct cnr WTT, g1Ql1i1, <1 I'i!Rl I'i!d I (repet itivity) g"1fidl\Jl"1 (recom bination frequency) cnr 'KIT 11m \.il'rfcn 3000 Mb 3lTCf)T'< cnr ct (mol ec ular mark ers) mur TfC!" t itq ct<:rR fMm 11m vm- fR<T (sex determination) (linkage) , g1Qlii1 (r ecomb ination) (gene ti c disorders) cnr 'KIT fMm 11m (d is ease marker mappin g) (d istance mapping) 3lTCf)T'< cnr 'l-fi 'KIT fMm 11m qRlll \Jl1 I -q J;"'$';chllOl ct 3TC'1TclT cnr 'l-fi fuJm 11m Cf2lT ct \3qRlCl'lI'i!i if >Iftnm ct m -q 'l-fi \Jl1"1Cl'lI{l f?1c;r -.:rACf -q fcrCl'lRr cnr >fT'<')q ct<:rR fMm 11m \.'Rr"fl1i(l 'lOfi 'll R'iCl'l QlOllCJ'i!uOIOl SHd Ie!,""! I $11 f.i Cl'l \iflTd" if vlTc1 >l \Jl1 Rl di fctcnm x-fqtA- 1R wrr fcnm \JfT "{gT I VlTQA, >Pffi, cr$rR if "Cl'lX x%" -g l -gr if fc'rfi'r;:;:r -;f ('1 Cl'l'it fflRCf vfr.l 31 jw U 1- em >l&1ftld "Cl'lX m l1RCT x'i cnr f.rcnrc;r fc;rm ll1TI I -g vlTc1 ctT fctcnml l vfr.l ctT fuJ'l"-fuJ'l" 41iilRlOll -gl qRdl\Jl11 2003 if ctT Cf2TT 31{f dC{i" \JlT >l <01'1 1 11 fl""l CfJ 3fT() -g, 3RX \Jl11S;Cl1 ctT ClldlCl'it U nl1 1f<jT: fcrwr, 'JITTUWl 273009 fliill1'1\Jl1 ctT \3ql11fl'ldl mfi1c;r cB;;;;c61l1 1R <fi tITR m ll1TI fcRf x'i \3qRlCfJI'i!i if l1111 11 CfJ'<"dT fcRf >fCfJT'<" ctT mtR:r cnr l1RCT ctT if >ll if if 51 sf) f.iJl "CfJT x-fqtA- S31T, \3X1 'fl'11[f ctT 311 j4 CfJ m 31jWl1 cnr=r if Cff<ft <n:lt 31l u IRlCfJ cnr fl i R?<1Chll1 Rl t:'j U I <fi fcnm ll1TI jl H) 011 CfJ 'it l1RCT x'i cnr <fi Rl ff1 d "Cl'lX fc;rm ll1TI l0f \3X1 'fl'11[f ctT ClldlCl'it U nl1 >lRlCfJC\('1, '1T1Cf)

mm-r: m :rem - NISCAIRnopr.niscair.res.in/bitstream/123456789/26953/1... · cF 31ltIT

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Page 1: mm-r: m :rem - NISCAIRnopr.niscair.res.in/bitstream/123456789/26953/1... · cF 31ltIT

~~t:;Ct \l~~tTR~ qq 10 \llq; 2 ~ 2002 ~. 165-174

'< fit Cf) I o:a \JllT~ ~ ~ \ifq >11 Ell fi'lchl ~tTR ~, 'l1ffifm ~ ~tTR m~

~ ~-110012

mm-r: -.:rACf ~ qRlll \Jl1 I ct 1:Tcf ~ -q WT'l11T ~ m ~ -.:rACf ~ ~ 3K<.R1 'iU3«1'"Fl :rem \3\JfTlR

~ ~I ~ ~ -q ~ ~ ct 3lR'lRl~ltOC 1@j3lT cnr 3rmT ~ ~ fuJm 11m ~I ~ qRlll\Jl"11 ct ~ m ~ -.:rACf ct ~, ~, xtq$1, ~ f.'rcrRur, ~, 3l1'jd~ICl'l, >f\iA"1", flliilf"G1Cl'l ~ ~iif<ftR'lCl'l fcrCl'lRr ct m -q ~ \Jl1"1Cl'lI{l ~ ~ ~ I -.:rACf Cfil~ICl'l1 ct ~ ~ 23 (22 + XX or XY) ¢f>llildlii'j ct ~ ~ cnr ~ ~ ~ ¢f>liil~ilii ~ ~ ~, ~ WTT, g1Ql1i1, <1 I'i!Rl I'i!d I (repet itivity)

~ g"1fidl\Jl"1 ~ (recombination frequency) cnr 'KIT ~ 11m ~I ~ ~~ \.il'rfcn 3000 Mb

3lTCf)T'< cnr men~, ct ~ ~ ~ (molecular markers) mur ~ TfC!" t ~ ~ ~ itq ct<:rR ~ fMm 11m ~I ~ 3l1'jd~lchl ~ 3lR'lRl~ltOC ~ vm- fR<T ~t.ffiuT (sex determination) ~igC'P1dl (linkage),

g1Qlii1 (recombination) ~ 3l1'jd~lCl'l 11'$<1~di (geneti c disorders) cnr 'KIT ~ fMm 11m ~I ~ ~ ~ ~ ~ (d isease marker mapping) ~ ~ ~ (d istance mapping) ~ ~ ~ l ~ ~ ~ '<'ffi<n/~ ~/~ 3lTCf)T'< ~ ~ ~ cnr 'l-fi 'KIT ~ fMm 11m ~I ~ qRlll \Jl1 I -q J;"'$';chllOl ~ ct 3TC'1TclT iil~C:1 Cfi'I~IOl01 ~ cnr 'l-fi ~ fuJm 11m ~ Cf2lT 1i1~C:1Cfil~IOl01 ~ ct \3qRlCl'lI'i!i if ~ ~ >Iftnm ct m -q 'l-fi \Jl1"1Cl'lI{l f?1c;r ~ ~I -.:rACf ~ ~ ~ ~ -q j;{1~~~fl fcrCl'lRr ~ ~ ~~ cnr >fT'<')q ct<:rR ~ fMm 11m ~I ~ ~ \.'Rr"fl1i(l ~ 'lOfi 'll R'iCl'l ~ QlOllCJ'i!uOIOl ~ ~ ~ ~ ~

~~~I

SHd Ie!,""! I

31T~ ~ $11 f.i Cl'l \iflTd" if vlTc1 >l \Jl1 Rl di ~ fctcnm ~ x-fqtA- 1R ~ wrr fcnm \JfT "{gT ~ I ~,

~, VlTQA, >Pffi, ~, ~, ~, cr$rR ~ ~ ~ ~ if >lIIRl~n('1 ~ "Cl'lX x%" -g l ~ -gr if fc'rfi'r;:;:r ~ -;f ~ ('1 Cl'l'it fflRCf vfr.l 31 jw ~ U 1- em ~ W1m~~~l1RCT~~em~: >l&1ftld

"Cl'lX m ~I ~ l1RCT ~ x'i ~ ~ ~ ~ cnr ~ f.rcnrc;r fc;rm ll1TI ~ I ~ ~ -g vlTc1 ~ ctT ~ ~ fctcnml l vfr.l ctT ~ ~, ~ ~ 31fl1f.i11~1 ~ fuJ'l"-fuJ'l" 41iilRlOll ~ ~ Ri1dl~I'it -gl ~ qRdl\Jl11 ~ 2003 if ~ ~ ctT ~ ~ Cf2TT 31{f dC{i" \JlT >l <01'1 111 fl""l CfJ Cf~ ~ 3fT() -g, ~ ~ ~ ~ 3RX ~ \Jl11S;Cl1 ctT ClldlCl'it Unl1

~ 1f<jT: ~ ~ fcrwr, ~ 'JITTUWl ~ fcr~~,

~ 273009

~ ~ ~~ fliill1'1\Jl1 ~ ctT ~ ~ ~ ~ ~ ~ ~ \3ql11fl'ldl mfi1c;r ~12 cB;;;;c61l1

~ ~ ~~ ~1~C:1CfJ'i~11('1 ~ 1R <fi ~ tITR m ll1TI ~13.45

fcRf ~ x'i ~1~C:1CfJ'i~11('1 ~ \3qRlCfJI'i!i

if l1111 ~ 11 CfJ'<"dT ~, ~ fcRf >fCfJT'<" ctT mtR:r cnr ~ CIJ'<ill~, l1RCT ctT ~ ~ ~ if >ll ~~ ~fl if ~e:r if 51 sf) f.iJl ~ "CfJT ~ ~ x-fqtA-~ S31T, x ,~ ~ \3X1 'fl'11[f ~ ctT 311 j4 ~I CfJ ~ ~

m ~ ~ ~ tT.~.~. ~ 31jWl1 qlcfl!{IRh\Y~ cnr=r if Cff<ft <n:lt ~jll . 1 2 ~ ~~-~~ 31l uIRlCfJ ~

cnr fl i R?<1Chll1 Rl ~&1 t:'j U I <fi fcnm ll1TI ~ jl H) ~ ~ 011 CfJ 'it

l1RCT ~ x'i ~ >ll~~cfl cnr ~1~clCfJ'i~l1('1 ~ <fi Rl ~&1 ff1 d "Cl'lX fc;rm ll1TI ~ l0f \3X1 'fl'11[f ctT ClldlCl'it Unl1 ~~, ~ ~ >lRlCfJC\('1, ~ '1T1Cf)

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166

M

1L;;'~~r:~~::~~~==~9~:-~~~~~;;~~~~:17:=~~ 2 3 7 8 10 11 15 16 16 4 6 1214 19 20 5 13 21

liffiA q;)ftrr L -fl M Q<l) I

l:Sl I I I I I II I I • I I I I II I I I I I I "II II I I ------I I I I I II I I I I I. II I I I I I I II II I I ------

I I I I I I II I I I I I I II I I I I I I II II I I ------I I I I I I II I I I I I I I II I I I I I I II II I I ------__ ..... _.9_ I , , I I I I. I I I I I I I I .. I I I I I I '1 .. I I ----- -

====================-======== - ------

fmr 1" - ~iffiA ~ ~~ ~ ~ ~ ~ t ~ ~ alIq'(~fi1'1 ~q;) ~ ~ -fl ~ ~ ~ <PI ~ fcl;mTImI

("<I» ~~q;) ~~ 1RRIl TIm, ~ ~ L -fl M Q<l)~m; ~ ~I

:~) 'CI1T<f l1 ~~<RI"1 ~ irnT ~~ ~ ~ q;) ~ -fl ~ cmcT TIm I

~ -chm- ~ fu<) -.m -g 1'6- IX ~ ~ -gt 1fRCT

fcrcnm qft :rem ~ ~ ill ~ -g-1' '!-11

~ 3ITx V® mu\t ~ !ctfqt:ren qft 41'<'l:qRCh

>I Rl Ch C'1 d 13D qJT 3l~ ~ -mtr fcfJm \JlT xm -g- c®' " \RCfi ~ lR ~ >rR ~ (qTf -.m -g r") ~ vftcR

ctI ~ 3rcmRUTT ~ >I\J1 I R1~l qJT ~ ~ ClldlCl,<uDll

~ ciJ·~ tWIT ~I >I\J1 I Rl~l ciJ >lIChRlCh ~'~~~" c

CRUT ciJ Ri <t; I ~ cf> ~ ~ 311 (Hll Ch "'{i)q ~ ~ fcnm \JfA1 '{jf.1 ~ d CfJBT m-rrr I ~ 3ITx V® >I I q Rl Ch

~ >I \J11 Rllll ciJ ~ ciJ ~ ~ ~ S3lT -g- c®' \RCfi >I\J1'if.1Ch ClldlCl,<ul ciJ ~-~ fi Tfi1d ~ ~ ~ vrR qft ~ ~ s{ -g-I ~ ~ 31'ligC'1'i

"ill ~ ~ 1fRCT \J1 'i fi (.~ I 31fdcrF~ cf> CfJRUT ¢::T S3lT

-g-I ~ ~ ~ 1fRCT m ~ ~ +i1 ~~I~ ~ ~ lR+i 311 CI ~ II Ch t 1fRCT «rti ~ fur.AT 41 +i I R ~l ~ +i I 'i Ri Ch

fc1fi l IRl~l ~ ~ -g-~ ~ cnT{ >llfOl\J1ld ~

~ m-rrri "l1Ffq ciJ ~, \3YVffil, 'ff$, ~ x~

fcrcnm m cf> ~ ~ ~ fc1 fi II f{'j II i ~ ~ -g 111-1(,

vIT '{j\J1 'i f.1<$1, ~:fffUrqft ~ ~ q $ >lTInm3D ~ ~ f.1 ~Gld ~ ~ ~ -gn l ~ 3IT~, fc1fi l lRl ~ 3lT~ ll'$"1~lli 1fRCT vrrft'r ciJ ~ ~ -gl ~ ~ ~ ~ f1cfRur qft ~ f>nm cBt \JfR ~ ~ ~ 3lJCl ~ ll Ch ~ I W ~ ~ fcrfcmd" ~ ~ Fc:Ch ~ \JfR

AA lR -gt ~ -g-j1X1') <rg ~ ~ ~ ~ ciJ ~ W1l cBt \JfR AA lR -crT f1 Lh C'1 d I ~ "f1Cfld1

-g-PO-31 ~ ~ ~Cq) tfq 1987 ~ ~Cf S3lT

~ I vIT 3lR.~.~.~ . ~ qx 3nt:1Tffil -g-I ~ ~ m--~ qJT ~ ~ it.1f-1.~ . ciJ~ fcrcnm W1l qJT ~ 3l~ CfJBT -g-I ~ 3!RlRcro 3RT

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167

xmuft 1 - l'fAq q)T ch ~c61 <l ~ li 1 ~ a Chi ~<l C'1 ~ ~ ~ S11~c?iCf)I~I1<'1

3000 Mb 16.6 Kb

fcrfl1;::;:r ~ 1f-l ~ ~31't cBT -msm 23 (XX If) <n 24 (XY If) ~31't "if ~~~.1f-l.~ ~

~ -{l X 103 >rfd ~ ~ ~ 1f-l ~ ~31't cBT -msm 23 ~ 10i 46 ~ ~31't "if 6500-80000

- 1/40 Kb

~ 'l1fl1

37

1/0.4 Kb

~

~-msm

~~

RtT1~re:q ~ 1f-l ~

(;:i~lFsht::;!11 ~ cnr ~ 'l1fl1 ~ -gt

(j ~ Fsh t::;! 1'1 CImfT % 1

- 3%

~

~ -93%

~ ~,gPc>1"l1 X SPl"llft'lS1 10i ~ ~ lR

~ X SPl"llftlS1 ~ lR

'5lel~'1i GDB (genome database), OMIM dbest, MGD,

Genethion , CHLC ~ CEPH tl

1. ~ (Genome)

~ ~ If ~ ~ 23 'j0I'1tii q)T

~.1f'1 . ~. t;1 ~ nm "{~ If ~,@C'1I~Cfi t;1 ~ XiIFf "{~ If l'fAq cF \iltq.:r qft ~ ~ ~ t; ~ ~ 3ITf.RUT, ~, ~ ~, ~,,{lRc61, 31IChIRc61,

31lj~~ICh ~ >I\Jl'1f.i¢ fcl~'lqdl~ mt ~ tl <rg »1,@C'1I~Cfi ~ 1f'1 ~ ~ Chl~IChI cF '4tm f.iti:::l0IChI{l >lfui<ll~ ~ ~ t;1 cr@ <rg q,<~,<Jlld 31lj~~ICh c;r~ em wfi1q:) Wl ~ 31R 1R ~ mxr mtR cF Wl If 31 jcY! '@ '1

CfJ'<"dT ~ t; 1'3.36

~ ~ ~ lil~C'ICh1~<l1 If ~ 31R 1R ~ 1ft >JltR:r q)T 31 jcY! '@ '1 ~ xgcf ~7.3X ~ ~

Wl ~ wft ~ J'llilRdi qft JJ~reCh ~ ~ ~

'd"2D Xil~reCh ~~Hi ~ qfm- qft ~ q)T ~ ~

31~ fuRrr \JfT ~I ~ ~ ~~ ~~ ~ ~ Ts vfR:r qft \JlHChI{l ~: m ~I 2. vft-;:r ~ (gene organization)

l'fAq ~ If ~ 37 li I ~ a Ch1 ~<l C'1 vfi';:r 'd"2D ~3l'"{ vfi';:r 65,000-80,000 "(1'q) i8 qft ~ t; I

~ ~ (gene density) 0.4 Kb lil~aCh1~<lC'1 ~ If 'd"2D ~3l'"{ ~ If 40-45 kb t; vfi';:r 3ncnR

~ 10-15 kb 6tn t;1 'd"2D ~ ~ 170 bp

6tn t;1 ~ vfi';:r ~ (gene organization) If dt.=r WPR q)T ~. 1f'1 . ~. "4Tm \JfTd1 t;1 ~eC'1I~c:, f?l'-llfleC'1l~e,

lil~ifi1'!.~eC'1l~e ~ ~'1'<I~RI 3ncnR~: (repeated

size) 5bp. 6bp, 1-4bp"(1'q) 6tn t; (xmuft 1) I

3. ~ 31jwliOI (genome sequencing)

l'fAq ~ cF ~ 31 jiflli 01 cF ~ l'fAq

qft men Ch1 ~I Ch I ~ ~ em f.'rcnTc;r fc;mT \JfTd1 t; ~ ifil lil '1i'lli em ~ el cB \Jl >rfCr{~ If 1:fC'1T Xi I ~ c:1 ~l e ,<

(flow cytometer) mxr ~2:fCI? CR' fc;mT \JfTd1 t; I ifi1 li'l Xi1 lil

q)T ~ ~ 'ifll1 cF ~ fuRrr \JfTd1 t; ~ ifi'l li1 Xi1li

qft ~ ~ -&mx CR' c;fI vrrm ~ I <rg "CfJT4 ~ ~ (dyes) cF ~ ifi1li1fflli q.-\jd1 (affinity)

cF 31ltIT'<' 1R fuRrr \JfTd1 t; I ~ ~ ifi1 li1 fllli

~ 1-8, 13-23"(1'q) q)T ~ 3ll"{1f;ft ~ CR' fc;mT

\JfTd1 t; I ~ ifi1 lil Xilli ~ 9-12 em ~ <IT 'ire ~ (Dot blot) ~ Lfill CR' fc;mT \JfTd1 t; 3fR ifi1li'J\(i1li

qft ~ 1f'1 ~ <IT <ft.x-IT.3lR. wmffif (PCR based) cDNA

CfC'll Pi 11 ~ ~ c;fI vrrm t; "\J1T ifi1 ~I {flli ~

6lcft t;1

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168

------------

ACCGTAAATGGGCTGATCATGCTTAAA TGATCATGCTTAAACCCTGTGCATCCTACT

~w;q ..

ACCGTAAATGGGCTGATCATGCTTAAACCCTGTGCATCCTACT

fmr 2 ~ ~""'~qi1~R I qq;iI?;~q;)~ mu~~mil<m~~~~~~1T<fT I

~ lroI"31 (~ if ~ ) qi1 liI;;;ft~ itt! f\lm FtlIl lJlI1

I:!'l ~ ~ FtlIl1T<fT I

.wr ~ sti' llilfJ1s:t cf;- ~-~-~ (end to end)

~ &RT ~.~.~. ~ ~ CR ~ vmf ~ (~ 1) ~ 3ftClx~rqll ~,,{Nc:.,(i ~ -gl ~ ~

'-'11"'11r:tCfl ~ ~ ~ "CflT xil1)cbcx mxr 1'I{C]O~CflxOI CR

fc1m vm=rr ~~ 2kb"Cl" 5kbqft cDNA ~ ~CR ~ \Jffi1T ~ (~2)1 ~ ~ ~-~ ~ QJll1 ~ c;m:n vm=rr ~3') Cf~ Ri cMR=i 11 ~ ~ ~

fclRn vm=rr ~I ~ ~ ~ qft ~ ~ ~ \Jffi1T ~I iT~: YACs (~31IaRh~I~('1 stillil xil 11), BACs

(31IaRh~I~('1 ~cRlRll('1 stillilxill1) ~ PACs (t<'lIRli~ 31Iaflh~I~('1 stilli'I'<ill1) -gl \34~Ck1 ('11~~~\Jl em ~ >frn &RT ~ CR fc1m vm=rr ~ ~. ~ (mother

DNA) qft ~ CR ~ \Jffi1T "51 .wr ~ ~ cp)fbT

~ YACs"CflT ~ 8-JOMb, BACs "CflT ~· 0.2-

0.4 Mb ~ PACs "CflT ~ 20-180 Kb 6Rn "5 Cf~ ftCfCf ~ em ~ cf;-~ ~ xf ~ ~ em 'TIT vm=rr "51 .wr Rh11xRl~11 dCfl1)Cfl &RT ~ cf;-~

1WlT em ~ fc1m vm=rr ~ I ~ ~ Rtf) FeFeCl

~."CR.~. Rh1IxRl~ll, ~ m~, ~ cp)fbT

+Wtrr QJll1 ~ ~ \Jffi1T ~ Cf~ ~ ~.tT.~. (STS)

~ em ~ fu<:rr vm=rr ~I -1Rf ~ fclfmrt ~ ~ em ~ cf;- ffi ~ ~ vm=rr~, ~ -g: q, ~ (zoo blotting) CpG 311~~o~ (CpG island),

~.3lR.~.~. ~ ~.~.~.~. (mRNNcDNA) , ~ ~ ~ (exon trapping), cDNA ~ <n ~ (capture) I <rg ~ "Cfll<l Rh '-'11 Cfl ('1 +Wtrr cf;- C'l6d" 6Rn ~r 1fcp (PACs) ~ xf ~ ~ i11T em tcRr (BACs)

&RT ~ fc1m vm=rr ~ I d~4xhl ~ "CflT ~~FeCfl *r ~ CfiBT

6Rn ~I ~ ~ ~ ~ ~ f.1tffiur, Xii5('1hldl ,

~'i4ll1'i ~ 311j4~ICfl ll"?i'1~""l'j "CflT11cf[ CfiBT 6Rn ~ I ~ ~ ~ ~ fl qft ~ ~ 311j4~ICfl fclfillRl

"CflT ~ 1('1 'i 1 Cii Cfl 3lur<:R ~ CR fu<:rr vm=rr ~ I <rg

~ "Cfll<l ~ ~ FeCfl +Wtrr cf;- &RT RCflI Rf14 ~Xi ~ ~

RCflI Rf) 4~ ~ imr ~ 3fR -4f1trr ~ &RT

RCflIRl14~xi ~ ~~FeCfl r:s~"{i cf;- m ~ LfCfT CR

fc1m vm=rr ~I ~ ~ ~~FeCf) ~ qft ~

~ ~I ~ ~ ~ "4fqTf (disease marker

mapping) ~ QJll1 1) ~ \Jffi1T ~I

~ ~ ~.~.~. i'1§'(i)4d r em ~ JJ~FeCfl ~ qft em ~ 1) C1'Tm vrr ~ ~I ~ ~ .wr CfCf) XCfd ~ (blood group) ~ ~ ~Il!)'I~FeCfl lilRlGlt1

~R~~Xi, ~.~.~. ~ ~ (HLA tissue typ­

ing), ~."CR.~.cfT."CR.tT. 3lR. (microstallites) fclCflRid

CR ~ llir -gl ~ cfK5 ~ (lod score) em ~ ~ ~ ll<lT ~ I \i1T +3 cfK5 ~ Gl ;;$\Jj ~ ~

~ 2 ~Cf<iCf"Ci'H'i (exclusion) ~~ Gl;;$\Jl 31tx <rg ~-~ *r cf;- Cfl~Cf~I'i cf;- ~ ~ Ri1dl~lx

~I

~~*r~cf;- ~, ~~, ~ ~, ~ ~ <n ~ cf;r:tC'1I\Jl qft

\Jll'i Cfl 1 ~ 1Rll 311 Cl ~ll Cfl "51 ~ 31 Rl RCh1 Xi 1 ~ a JJ ~ FeCfl

stillilXill1 tCfl ~, ~~~I'i *r, ~ m il"q,

~ m ~, ~ ~."CR .~. ~ il"q {f'1T'iT

31ICl~~Cfl "51 '

~ ~ ~ctXUT (gene transfer) , qft "{f~

~ ~ ~, R~ClI~xXi (retrovirus), Gl 41 x{111

~I'iidxol , q)1i1Cfl('1 ~ ~~~4'1~~ 1 'i (chemical and

electroporation), 111~stil~;:JjCf~1'i 4I R;cOfl('1 /OI1RlI;g~c ~

wfiic;r -gl ~ ~ ~ cf;- &RT ~ ~ ~ qft ~ c

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¢f)'P:f1 fl1 Ii ~~~1Z ~ l'fT'.n Mb ~ ~1Z %

1. 250 8.3

2. 240 7.9

3. 190 6.4

4. 180 6.1

5. 175 5.8

6. 165 5.5

7. 155 5.1

8. 135 4.5

9. 130 4.4

10. 130 4.4

11 . 130 4.4

12. 120 4.1

13. 110 3.6

14. 105 3.5

15. 100 3.3

16. 85 2.8

17. 80 2.7

18. 75 2.5

19. 70 2.3

20. 65 2.1

21 . 55 1.8

22. 60 1.9

X 140 4.7

Y 60 20

\JfR ~ cf> ~ <;:i'{dPiCb ~ ~ c:JCfi)cI;R"i +PA,

CFTR, g) Ii~P ('11 RH ~~l 41 "! ~"i ~ "! rtl ftftft"i ~

31 1j)4~ICb cl'{~rell ~ If m ~ ~I '~ flll ~ldlCfC' 'CbT ~ ~ ~. <f"i".""!". cf>

xr4T ~ (A,T,G,C)'CbT wfi'rcp- 31j)s:tJ~UI ~ ~I ~

~ ~ ~ fctfu<:rt 'Cf)1ll If ~ ~ % I ~ c41A ~I"i fcliU ~ cf) lfl Cb C'1 ~~;S~I"i fcliU I ~ xf ~ fcliU If 31j)s:tJ~UI cf> ~ ~ ~ ~ \Pl""!" ~31T 'CbT ,,!0Zij1~~

169

~ ¢f)1 '"11 fl1 Ii ~~ 3fif (fC!J ~

lfq fcnm -;:;fR ~ -;:;fR

Mbp*

0-255 1240 1234

0-243 750 743

0-203 662 649

0-205 489 486

0-181 549 546

0-186 736 731

0-160 559 550

0-144 403 395

0-144 403 395

0-140 432 428

0-146 726 721

0-142 659 658

0-117 216 208

0-111 389 387

0-000 363 356

0-93 486 478

0-83 709 701

0-81 188 178

0-75 779 775

0-65 350 341

0-48 137 134

0-48 310 309

0-143 512 510

0-59 53 48

~ '{i~c'lt'jol ~ ~3i'icl~~{l ~ ~ fcnm \JfRl1 ~ I ~ cf)41ChC'1 ~~;S~I"i fcTfu If ,{,{il~H'i &RT ~

~311cl~~'{i Cfh qJC ~ fcnm \JfRl1 ~I

${ C4T;)~H i).~.",,!". 3ljwJ101: ~ fcliU If ~ ~ ~. \Pl.",,!". ~ vii ~ ~ ~~ ~ m % ~ qlc>ll"!s:tJI~C'1"!~I~~ ~ ~c:J~Lf)l~RHi ~ ~ Cf)'X 'Fc1<n \JffiIT ~I ~~: 10 xf 1500 ~311cl~~{1 Cfh ~ ~ qft ~ If >W<f fcnm \JfT ~ ~I ~

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170

~.~.~. ~ cpp:f ~ c;rrm \JffiTI ~I <rg ~ ~ fctfu ~ ~ ~ ~$11f.1Cf)1 ~ 1972 ~ f~Cf)Rid em 0t1

cf)41CbC'l ~!l~~H 3lj~JiOI fc)fU- : ~ fi'Frffi >f2:fl1

fctfu xf ~ ~ ~ fcn ~ A,G,C,T 3l~3TI em ~ ~ em \JfRfT ~I ~ ~ ~ fTrc;wt ~ X'R 1977 ~ ~ fcn<:rr 2TI1 ~~: 'G' ~ Cf)T ~ fcn<:rr \JffiTI ~ 1 >f2:fl1 ~ ~ ~3TI em ~~ ~ xf \3 q ill Rd fcn<:rr \JffiTI ~ 3fR ~ ~ f?r~ wr em ~ ffrr cfi G ~~ xf vfR;r \JffiTI ~ 1

~ ~ G ~ ~~ cfi Be; ~ \JffiTI ~ ~2TI Cf(>j"I~0'1 ~ cfi Be; ~ ~ ql~{)~1 cpp:f ~

c;rrm \JffiTI ~F ~.~.~.Cf)T ~41~cYl ~11 ~ -crrcYl- ~'"'Jjl~~ %: ~.~.~. qlC'11~~01, ~Fcfc;j~01, ~, 3fR ~1~R:hcb~11 ~'"'Jjl~~ ~I ~.~.~. em CFcffi ~ cfi Be; lC'IIPi;S

~ ~ MI3 ~ cpp:f ~ c;m) vncf %1 ~2TI ~ ~L<'11cbFeCl >fW1 ~ fcn<) vncf %1 4JIPi;S 'l-lT ~f cpp:f ~

~ -gr ~ %1 ~ ~ ~ ~ ~R cB- Be; -qr m 31R

em cpp:f ~ c;rrm \JffiTI ~ 1 ~ ~ ~ ~ ~ ~ ~ Cf)T W W11 'Till Cf)X fc;rm \JffiTI G 1

~~3ljw~OI ~~fctfu~l~ cntf x~ ~ ~ ~ ql c41 ~~01 cfi ffi ~ cpp:f ~ c;rrm \JffiTI

~I ~ Be; ~ ~ ~ ~ ~cfi ~ 1R-~ ~ ~ ~ em 'l-lT cpp:f ~ c;rrm \JfT x=rcPclT ~ 1 ~2TI ~ ~ ~ em 'l-lT ~ -gr \JfRfT ~ 1 ~ Be; ~ Cl ~~C'I ~ ~ ~ ~ LfC'11~fic ~ cpp:f ~ c;m)

vncf %1 ~ 3lla~R:Cf) ~~ ~~ Ri ctCi R1 J I fctfu 'l-lT %T \JffiTI ~ 1 ~ 3rlf x-rmcr11 ~ ~ ~ fufu<TI xf ~ Ri ctCiR1 J I em \JfRfT ~ % t ql~{jRictCiR1JII ~ fctfu ~ ~ m~-m~ ddNTPs xf ~ cfi X1T~ -gT W11 ~ ~I 3fR ~311CI~~~i cfi ~1Cf)1~4'1~~11 em c6)JilC"gJ~11'{~~ ~ f;RT 'Till CR fc;rm \JffiTI ~I ~ ~ 3Km~ fctfu firq ;?;Cf'i'IC'lIU1"1 em cpp:f ~ c;rrm \JffiTI ~ ~ fctfu~ ~ ~ ~ firq em ~ fcn<:rr \JffiTI ~ 3fR ~ Cf)11 lbl Cf) C'I ~ I ~ ffi1 '&)141

em \JfRfT ~I

~ l:R ~ ~ q;) ~ (alignment of DNA se­

quences)

~ Be; cff.:f fctftmt cpp:f ~ ~ \JfRfT % 1

WfcTR ~, CfC'IT1" ~, ;S1~~cR;S WfcTR, fC;r;:ffi

3lIcrx ~ ~ ~ ~ ~ em ~<f fc;rm \JffiTI ~ 10f ~ CfC'IT1" ~ ~ CR Be; uffii % 1

~ ~ cfi ~ Xi'l-lT qR OIiJil em ~ 10f ,.,.-r.XjCZj"....Clrt-;~ ffi xf ~ ~ cfi Be; Iill~ cfi 3l jw ~ 0 I

~ 10000 bp 1R 11ET ~ ~ 31Rt ~ 1 ~ 3lci

<rg S3lT fcn ~ ~~I ~ C'I Cl cfi ~ ~ x~ 1R 31Rt ~ (XiRU1t 2) 1 <rg ~ ~ (1996 ~ 1997) ~ "d<r S3lT 2TI1 ~ ~ ru~ll'Cdl <rg '~ ~ ~ fcn 97 ~ ~ ~ Cf)T W11 ~ ~ ~ ~ ~ ~3TI 1R ~ 10f ljl~{qRCf) ffi ~ Xi-gT ~ ~I

~ ~ ~ ~ ~3TI cfi oRr W11 cfi ~ xf ~~11 ~ 'l-lT -atcD ~ \3qgCki ~ ~I Xjf.1 fVi:Jdd I em eft[ 10f \3QgCki CfRR ~ cfi Be; ~11~~11 ~ ffi xf ~ ~I Rlf)e1FeCl ~ ~ ~ ~ \Jffii 1R f?RT '{l~C'lI~c ~ ~1~ffi'I'{~~C'lI~C ~ % ~ UlR mT \JffiTI ~ I

~ Pt4fcR1 ~ ~ ~ 1R vii cpr4 fc@Fr ~ ~

~ xm ~ ~ ~ ~ cpr4 X'G{ 1R ~ 3l"\H1~~ ~~$lldl ~I ~ ~ ~ Cf)T W11 fcnm ffil~I{11~

cfi ~ mTf ~ ~ CR M 1R ~ ~ CR fum \JffiTI

~ 1 <rg Xi'l-lT cpr4 Vf"l ~ cfi f%cl cfi Be; cpr4 CR ~

;SICI~~ ~ DDBJ, EMBO m ~ ~ qm1 %1 ~ ~

3ljw~OI ~ CRM 1R~ ffi xf Xi'l-lT cfi ~ ~ c;rR em ~ ~ f?rc;r \JfRfT ~ 1

l1T"fCf ~ 3l jw ~ 0 1 xf vfiq fct$1R cfi futn:T ~ ~ ~ ~ ~ %, ~ Xi~ ~ ~ l1T"fCf

~ cfi \3wqC'l ~ em x-icbdCf) %1 <:rR <l QR~10111 ~ em cpr4 ~ em ~ 3RRGR eM .~ ~ ~ ~

~ w en-~ ffi xf 3lllT 3lR cnc;lT ~ il<T 10f ~ T>f'l1JCf xf ~ xg ~<TT 1 ~ X1T~ -gr PlCl1Rid l=fRCT ~ cfi ~ilj~If£lCf) 3JTCRUr, Xi'RfdT, ~,

ftrlill ~ ~ 1JUTtf11T Cf)T ~u1 ~q) ~ fcn<:rr \JfT ~I ~ X1T~ -gT ~ ~ ~ ~ ffi xf Cli d I Cl~oft ~ ~ xf ~, xTriT cfi ~, l1T"fCf cfi ~i«flfdCf) 10f ~1)1~$11P1Cf) ~ ~ ~~ ~ f.1~1 ~ X1T~ -gT fct$1R cfi ~ 3-~ xf "'l~ 1R ~ ~ l1T"fCf -vrTfu, ~i i «ll R1 Cf) ~ 31Tfficp ffi xf ~ x~ ~ ~ ~ ~ XiWf 6Pft1 ~ m ~ J1 ~ I R~l cfi ~ m xf l1T"fCf xrcrr ~ ~ fu-q:)rn Cf)T

x=fq$r -gr ~ 1

~ ~ Q Rd10111 cf ~. m xf V)q fu-q:)rn

em ~. fili ~ I ru ftl Cf)T V)q~ R1 c6) ~ \rci 01 Cl ~ I ~ I ~ PI Cf)

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IDffi LfdT cg ttrm 1Tm t I ~ ~ x=Mc;;:r, ~'i gUH,

~ ~ \3 01 RCl ct 'i -ffit ~ t:fRT CflT LfdT cg ttrm ~I ~ ~ cfR lR JCl'<I\(il~~Cf) cw.r cB- 3lR

~ ~ xT fcl Cf) Ri d 6T'11 ~ mt1-'1" -ffit ~ Ii) ° I Cf) I ~ Ii 5 ciPiO)

~ ~ -ffit Cf) I ~) Cl"I Cf) ~ xi '<i! 'i I Cl"I Cf) Iffl1cfT CflT ~

"5T ~I ~ ~ ~ RCf)I~~~1'i ~ ~IiIR~'i -ffit ~W -cp) q)l1 CRill t 3fR ~ 1fCf) ~ ~ ~

-cp) I1f'<UT CRill t? ~ ~ >1ICflv1lfcl~'i (prokary­

otes) ~ 3"118v1lfcl~'i (eukaryotes) il ~ ~ t? om ~ ~ cB-~ -ffit fcp.:r -fcp.:r >11 fill (Tj I d xT '<i Ii I 'i d I

t?~ ~ LfdT c;rrr ~I ~ ~ ~ ~-ffit ~ ~ ~ t l ~ xT ~ -ffit ~ ~ (possible gene frequency) CflT LfdT c;rrr ~I 3"1'<iIIiI<"\!01

~ 3ITcR ~ ~ ~ ~A1<:1IRh<$~I'i, Rl('j1<$~1'i ~ ~CflT ~ ~ ~'<1Cf),<01"5T ~I J~~Cf) RJJ~\(n

CflT ~ ~ vTI ~ -ffit "\('[1'fR cnm GmClT -cp) ~

t. ~ ffi xT liTcf1 "5T ~ I ~ ~ fctcnm il ~ ~ CflT ~'ic4Cl\(~ ~ ~ tl ~ ;Sl('j1<$~1'i ~ ~ \(ilfiftjll (domain suffling) CflT -q;ot '" ~ ~ ~ ~ tl ~ ~ -ffit ~ (ori-

gin of introns) ~ ~ xT ~ cB- ~ il ~ liTcf1 cgttrm ~I

~ q Rd) (Tj 'i I cB- ~ ~ xT 3RIT11f'<UT ~ xT ~ fcl \(i II Rl ~'i -ffit cnm ~ -cp) ~ il -q;ot ~ ~I ~ cB-~ ~ '<i1~Cf) ql,<\(:qRCf) ~dl(Tj'i CflT

~ -q;ot LfdT ~ ~I ~ ~ ffi xT ~ ~ ~ 3"1lj~~ICf) ~IiIR~i ~ il3lT ~I <) fclCflRl~i

>1Cf)Rl(Tj<"\!01 ~ cB- XTI2l-XTI2l ~ ~ OCP 1fCf) ~ xT co

~ ~ il ~ ~ ~\JfldI ~~ ~~ ~ >rCf)C ~ ~ ~ (Tj 'i \(i cc<j I il CfflT ~ t, ~ 1fCf)

~ ~ ~ -ffit RPm -cp) ~ ~ tl ~ RiF«:Cf)

If)1~~lRi'<i, 1i&tlR1C"l «t>c>l":lRi\(i, 2:l1~,<I~;s~, ~,

cffm- ~ ~ cB- ~ il -q;ot (Tj I'i Cf) I ~ fi'rc;f ~ om ~lf)~~I~C"l ~ ~CRl~~I'i fcr~ ~ ~ cB­

~ il LfdT ~ ~I ~ ~, J~~Cf) ~, 1i1~~~I'i, pft~~I'i , q')l'i\(~l~, ~~I'i (\301RClct'i),

qlC'11lili1f>\J'li, ~ RJJ~C"lI\Jj1 (gene genelogy) cB- ~ il LfdT ~ ~ I ~, 3"11 j~ ~I Cf) ~ vflq Vfc:r fctcnm cB- ~ il ~ CflT ~ m"5T ~I ~ Sf)'1>j')f111i,

~, mt1-'1" ~ ~ xT ~w cB-~ cB-~ il -q;ot \Jj I 'i Cf) I ~ ~ "5T ~·it I fctcnm ~ CflT ~~ ~

~ xT >1 (Tj IRl d i cB- ~ ~- ~ CflT ~ LfdT ~

171

~I

~ ~ cB- (fg(f m ~ lR tIlR m vrr

X5Tt~~: ~~"l1RCTctT~, >11Cf)~Rl5IRi Cf) (Tj 'i \(i cc<j I Tfl1'i" ~ \(i Iii I RJJ Cf) ~, 3"1 j~ C"l 'i ~ ~ Ii I R~ i ~.;>\.-,- ' ~~ , , ~ 'rl ~IX Lf)1 1Cf) ~41C"l1V111

~~~cB-~XRdT~1 ~: \JlR 3"1ll~~~I'i ~ (GAT) cl,<ll~;S ~ 31fCf)

ttl'<l1fi:hCf) ~ (targeted killing of specific ce ll s), cl~~~ ~ Cf)~CWI'i (targeted mutation correction), cl'<"I~;S ~;::g)fc:l~I'i 31fCf) ~ ~CRi~~1'i (targeted inhibition of

expression) , ~ ~ ~ \JlR ~l'iid,<ol ~ ~ \JlR ~l'iid,<ol il ~~ I Sf)l.j'l\(illi cB- XTI2l ~~~~;S

~ \rci -;:fA ~ ~ ~ ~;S ~ CflT ~ LfdT wmn vrr

wmrr tl \J~IGld'< ~ ~ l'llaCblRi il ~~f?;j~'i ~ -cP) "Cf)l11 il "C"lTm VfRfT t I ~ <) ~ ~-ffit

BUr ~ m ~ ~ ~ ~~ClI~'<'<i ~, m RiA1c4CRl, ~~, ~~'i'IClI~'<\(i ~ ~ f?;j41\(illi

"Cf)l11 il ~ \Jfffi ~ I

~

• ~ ~ 3"1 jwli 01 ~ \J'i" ~ CflT LfdT CR'il

vTI GCfT cB- m xT ~ \RlTGT >rmfcrcf ~ ~, ~ ~ CR'il ~ ~ ~ ~ fcl\(ilIRl~\ JIIiIR~'i ~ ~ tm'fCf) ~ cB-~ ilLfdT CR'il1 3"11 j~ ~I Ch1

cB- '< I \(i I ~ ~ Cf) <tf€Cq')1 ° I xT ~ >r'liTfcffi vfT'11 -ffit Cf) 14>1 011 <:11 m lR CfflT-CfflT ~ 31'<'R ~ t I \3GI5'<01 cB- erR lR ~ -S'lqllil~'i cB- ~'i~501 lR

cnm ~ ~I ~ 3RT lil'i'I~if)'i <;:i\(i41cfllR cnm ~ ~ ~ \3GI5'<01 t ~ ~ cB- 31j"flR G­

mt1-'1" -cP) ~tR qffi R~ LCfI CflT th~ xn c I ~ JJ ~ I 'i ~ wfi ClJRUti -ffit fTh ~ I fcl fu cpT ~ ~ ~ ~ ~ CflT Cbl ~I Cf) I ~ ~ ~ ~ lR fTh ~ I Cl"I Cf) >fl1TCT

CflT ~ CR'il WIT I

• ~ cB- 3"11~RCf) am 3"1jwliOI -cP) ~ ~ ~

~ il ~C"lf\§JCf) ~IiIR~'i ~ 3"l'ia~~ ~lIiIR~'i ~ ~ CflT LfdT fcpm 1Tm t 3fR <ffi ~ tIlR il Xffi

1Tm t fcp m CflT IDffi ct-m 6T'11 ~ I ~ ~ irlt ~ cB-~ CflT LfdT ~ ~ ~ -gr fcpm \iTT wmrr t l ~ ~ ClTR TNFR ~, 3T~ -gr(1 -gr il LfdT ~ ~ ~ TAla, OPG ~

DRS lR tl 3RT mt1-'1" ~ TGI, MI, ctg 13384, 53

OX40 ~ GI MI, ctg 13980-78, 3RT ~ % B7

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172

~, CD80 1;fCf CD86. o:Rl .~ Tf<ft ~ -g SIRPexHHLA, MCAM, CXADR, IL6, CNTF 1;fCf

ChI~di<:JRh'i -1,IL-1I1;fCfIL-1 21 ~ ~-q 31fuco iT 31fuco $ m01 C'll V1 'I ChC'l ~ em ~ ~ cfi ~ iT ~ ~I \3cqRClJ'i 1;fCf

41 Jl 'ilfQ5 \A cfi 3fTtlR 1R ~ 1;fCf ~ cnm em ~ 'Tm ~I ~ -qcn \3\AAlC'l ~'XDT ~ \3cqRClFc'id

~ qft ~, AIRE ,,!~il¢bl~'i 31la$~f.'l~ 1;fCf

~ $4Cf~I"fl ~I ~ x:r4cfi ~~;gc ~ em ~ f.'l Ch 1 C'll 'Tm ~ I ~ fc)ftrsc ~ ~ ~ fc)?

Xj4'(RJ\C1V11'i ~~ 'i1$<:JXiR<:J1 (ENU) qft ~ iT ~ \3cqRClJ'i'i em ~ Wm 'Tm ~I

• ~ -gr -q 'qR v1RP1 ~ ~1fUT ~ 83fT ~ ~ -g: ?'1cj}0Jfl${[)V/ ?'1RR1{[) (Saccharomyces cervisae)

"[TT-X-c, ~:)"fitf1nC;-TT ~tC;-T~TT,h-cx (Drosophila

melanogester)~, m;:f;~i56.S1$~ V<>fti{~

(Caenorahabditis elegans) pfii 1;fCf EfrqT ?'1fi12fM(-f

(Homo sapiens) 11ACl"1 ~ ~ mit"'iT Cf>T

gC'l'iI~Ch 3l~ fclJm 'Tm ~I ~ m ~ -q CfiR {l iillJlf.'l ~Xi qft ~ ~ emf ~ ~ I -qcn cmc Ch~Cf'ii cnt PF'i" XiiillJlf.'l~Xi ~ ~ iT ,,!~flls{j "dCf) ~ cfi ~ 'qR ~ ~. Y, III 1;fCf a I ~ -g l

• ~ iT ~ Xi iillJlf.'l c -qcn Ch ~ Cf{j cfi ~ -qcn 3lc;rT cnm ~ ~ "'IT fc)? c;fj <$ C'll $ d! ~ I'i, ~ l@ ~ I'i

1;fCf Ch ~ Cf'ii qft ~~ "CfJ"Tll1 ~ cfi "ffi~ ~ ~ I ~ ~ ftR ~ qft ~ qft ~ ~ ~ -g: SNARE cmc Ch~Cf{j, Rab~ Sacl ~ cB~Jl\Jj I

~ iT cficrc;r Rab ~ 6t lJI41'{~CiC'l,( ~ iT 'i c>e1 '{~ CfC'1 '( ~ 1;fCf qT[ "dCf) 1lTt \iflCfT ~ I ~ x:rm cB ~ Jl \Jj "Cf)1 11RCf -q ~ fcffilR 83fT ~ I \Jffit 1R

611 em) -g 35 SNARES, 60 Rabs 1;fCf 53 cmc Ch~Cf{j XiiillJlf.'l ~Xi I ~ x:rm iT ~ -q ~ ~ qrc;ff

~ cfi ~ -q LfCIT "('iT[ ~ I

• v1RP1 cfi ~ ~ ~ -q iT Cf)'I~ICh01<:J ~

~ ~ q)Tf -gl ~ ~ w ~ cfi ~ "Cf)1 LfCIT "C.f)X fu<n 'Tm ~ "'IT ~ >fCfJlX -g I ~ ~ 1;fCf ~ ~ ~ vIR cB~ ct'1\Jj ~ ~: ~ -g ex 1;fCf ~~, ~ 3lc;rT-3lc;rT

TlR\JlR LfdT ~ ~ -gl ~ -g ex ~ ,(il$aL{>jI~Ch,

Arp ex 1;fCf ~Arp 71 1;fCf B, Arp I I ~ I ~ iT WASP/Scar fuT.:rc;r c;J,(MCf~1'i mtR -gl "'IT fcp ~

fi:bC'lliic"Cf)1 Arp 2/3 ChA1~Cf'ii"Cf)1 ~"!~I'i ~ ~I ~~ ~"'itT ~ ~I ~ ~ WH2~ ~ ~I ~ 3lffiRCfd WHI 1;fCf WH2/A or A, 1;fCf

GTPase ~ ~ ~ -gl • Cf)'1 ~ 1 Ch 1 iT ~ >ftit;:IT -q 'ii 1 $ FcfC'1 "fl 1;fCf ~ ~ XiI$FcfC'1'i ~q~"'C ChI$~\Jj (CDKs) -g M iT CdK 'HI$FcfC'1'i ~ ~ CdKs (CdKl, 2, 2,4

1;fCf 6) 3fR 'qR 'iil$FcfC'1'i CfC'l1'{~\Jj (cylin, A, B, D 1;fCf

E) ~ -gl "'IT Cf)l~IChI rw (cell cyc le) em f.'lJ8ld

~ ~I ~ CDKs (CDK 7,8 ~ 9) 3fR ~ XiI$FcfC'1'i CfC'l1f4\Jj (cyclin C, H 1;fCf T) ~iXiffu~1'i em ~ ~ ~I ~ -q, ,,!cR1~ftll ChI$~\Jj -qcn o:Rl CdKlcyclin ~1, 3fR ~. :Epftid (bud­

ding) ~ -q -qcn ~ DdK ChI$~Xi m fTwrC1T ~I Cf)l~IChI T@" em- 00 cPT xl" ~ cfi ~ q')1,&)1,(1$&~1'i 3lfu 3lICl~<:jCh ~I

• ~ v1RP1 cfi 31 j¢b'i UI iT 3{q "dCf) 30 >r'BTCft R'i~RiCl 31l;;:P'IV1'1'i (tumor supressor genes) 1;fCf 100

iT \RlTGT ~ 31l;;:Pl V1 'I 'i "Cf)1 -q-ffi "C.f)X ~ 'Tm ~ I

~ ~ ~ftcn wm~ Xil'il;:>[j 10t -;ft31l L{>j 1 f«:Ch ~ -q ~ ~ -,rp) -g I

• ~ v1RP1 iT ~ "dCf) 10,000 '<l IIChI~ ~ "Cf)1

LfCIT "C.f)X ~ 'Tm ~ 3fR ~ ~ cfi cnm ~ ~3lT1l)~, ~~~~~~ 3ff1l) $ 'i ~{) ~Xi ~ ~ ~ cfi ~ "! <'11 fc;j Ch ~ ~ "! "'C'{i

~ -q ~ -,rp) -gl '

• ~ ~ v1RP1 3lj¢b'i UI ("4"q) xl" 1.42 ~fc;j<:j'i fufTrc;r ~~ (SNPs) fl1#i ~ I ~ 1.9 Kb

em ~ SNP cfi ~ 3fTmr tHfCT ~ ~I M xl" 60,000 SNPs ~ xl'lWT (exons) -q 1lPfi \iflCfT -g 3fR ~ ,,!<'N'I"fl -q iT x:rm "('iT['lfTf 5Kb cfi ~ ~ -gl ~ 3lffiRCfd 971,077 ~~,~c SNPs ~

~ ~I ~ ~ ~ CfC'1R:r (BACS), PI CfC'1R:r (PACs) cfi 31 j¢b 'i U 1 iT LfCIT qft ~ -g I

• ~ ~ v1RP1 ~ iT ·c;rT[l lT[ 50,000-70,000

"dCf) ~ v1RP1 -q ~ ~ qft w:mCRT ~

~ ~I ~ m ~ ~fc)? ~ ~ ~ \KfTCn '41 iT ~ ~I

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1. ~ 1ft m, ~ (1999) 2137-2147.

2. ~ 1ft tt, CfR ~ ~, ~ ~, ~ 1ft ~ l0i ~:[[ ~~ UMla'?1 ~~Jffrp~ ~.T{ff.\[. 76 (1979) 1967-1971 .

3. ~ 31R { <kcn 1ffl, ~ 1ffl ~ l0i qrc;m:[ tt m, m'?:fJa'?1 ~ ~ Jffrp ~ ~.T{ff.\[. 77 (1980)

6715-6719.

4. ~ tt 3lR. ~ ~ l0i ~, tt -c;c;r, vfi~ 3llFvR1 3ITQ) ~ 'i1~c?iCfil~C'l tt.~.~. Q)1~C1H~R:CtJ ~nfiTl1 ~ mR~, fm:cl1, Cf77iIc;r. 41 (1992)

111-124.

5 . q;~{l'i l 'i 1ffl, ~ ~, CfR ~ ~ l0i -crr<f, "lffT, m ~ (1999) 78-81 .

6 . ~ eft ~ l0i fcR:R ~ m, ~ 179 (1973) 1144-

1147.

7 . ~ 1ft, ffl 360 (1992) 641-646.

8 . ~~ l0i ~, ~ <11~, ffl 39 (1998) 917-920.

9 . efU1C'lc'i ~ 31R, ~ 255 (1992) 737.

10. -;ft ~, ~ 3ITQ) CfiTs:R ~ 3ITQ) ~ 'i1~c?iCfil~C'l tt.~.~. 'i1C11Cf1@'< 01 I lOll C1l"11, $<iI<>1.~H, 9 ( ) 1176-1178.

11. CfiT'i 31R -c;c;r, «?i'iRi5'1 ~ l0i fcR:R, ~ -m, ffl 325

(1987) 31-36.

12. "11cq,1R101 { ~ 3flTP 'i1C11Cf1@'< $q)<>1.~Fl, 47 (1998)

146-155.

13. ~ ~ 10R1l0i (>\T ~ 1ffl, «R:'{tlCtJC'l ~ 3ITQ) ~ 3ITQ) ~ Ji~R:CRl, 133 (1993) 693-609.

14. ~~, «R:'{-t)CtJC'l tf~ - <:T ~ ~ ~ <ITt tt.~.~. 41C1"I 'il["q,\il1 Ji~R:CRl, 1231 (1989) 585-595.

15. ~ ~ l0i ~ 31R, tt.~.~.~ . 1ft. tt.~.~. ~ QIC1"I'iI["q,\il1, ~ ~~,<~FcR:q ~ 1fiR ~'{-t)M~ '1 ~

Ji~R:CRl ~ ~ tt~~. ~ ~, ~, ~. ~~1cf;i!1'i 0I 11Ol1 {l1~""'<i, 11 (1995) 621-625.

16. ~ 31R, ~ ~CllC'"lf-l I'i (~ ~ ~, ~.~. 1999) .

17. ~ ~ 1ffl, ~ <:T ~ RCll&,:pl'i, RlgR1lOll'<C'l ~ <M1C'l1,,'[)CtJC'l ~ ;o:fR <:T ~ 3ITQ) ~ ~

(~~ 1ft, ~m (1989) 62- 108 (~1'11ClFfltl tRr~. ~.)

18. \J!T'iCl'; ~ ~ "!. 10R1 l0i ~ffi ~ >I) '?:fJa'?1 Jffrp ~ Jffrp ~ ~ T{ff. \[. (1997) 1276- 1281.

19. fctc;qft it, ~ ~ 3ITQ) <:T ~ ~ ~ ~

~ ~'""4C11cf;i!I'"fl, ~ ~~, ~ <:i'ict. 20. ~cf;, ~~3-i'I~'iI~Jii!I'i , ~.:mfqr;<1'i ~

173

~~C'lQ~.c. 5 (1995) 315.

21. Q)T31T ~ 1ffl, ~ ~ ~ ~~'<~i!I'iC'l RqlC1;i!I'i,

~ 96 (1985) 315.

22. ~-c;c;r~ <:T~~~~, 117 ( )

459-465.

23. ~ ~ 1ft, 3'l1~'{11c1i!1'i 3lTrP ~ >nTll ~ tt.~.~, ~ .:m fq PI <1 'i ~, fch;tt ~ x-RT, ~ <:i'ict.

24. ~ ~~, ~ ~ CtJ~'1 1994 ~, ~cf;~f?lCtJ tRr ~ <:i'ict.

25. g>'iT~, <:T~~~~~~: 3'l 1 ~~ot)lf)I~ '1 <:T ~ 3IT'i" ~31&f fcR" Rcl~i!I'i, 39 (2) (2001)

158- 160.

26. ~ 1ft~, 3/)'!Cf))&/MI, 90 (1) (2001) 3.

27. ~3l1"(f ~ ~, ~ ~ cf;, i>fTACRJ.,&/'? ~ 7 (5)

(2000) 229-231 .

28. ~~, ~ ~'""4C11cf;i!1'"fl 3ITQ) <:T ~ ~ ~, ~ ~ k l.!?1)Rll.!~',!' 29 (1) (2001) 35-47.

29. fi'n:rr<1l1ffl, ~ <iT<Rt. 49 (2) (2001) 139- 149.

30. ~ ~ ~, ~ eft ~ l0i "C1: m -m, ~ Cf),am&/TvfI

f?riIi; 3 (3) (2001) 198-207.

31 . ~~, ~~~l.!?1)Rll.!~H, 29 (1) (2001) 35-

47.

32. ~ -xft ~, k ~ ffflrf. 3 (3) (2001) 22 .

33. ~ 31R, Ji~R:CRl ~~, ~ ~ ~'""4C11cf;i!1'"fl 3ITQ) <:T ~ ~~, ~ >l'rm1. 82 (2) (2001 )

22.

34. xt'j~~, <:T ~CtJI1'If?lCRl 3ITQ) \;fl""l'If?iCRi "SIR." ~ ~ ~~01~< ffiTTr 17(3) ( ), 35.

35. ~ m, <:T ~ ~ ~, ~ f%«?i~CtJC'l Q{\~ FcR:q, l/5)'{t/Cf)) $ Cf)H){i)CRf, 2 (1) ( ) 37-49.

36 . ~ m ~, "{l11 ~~ ~'""4C'flcf;i!Hi 3ITQ) <:T ~ ~~, ~ 2 (3) (2000) 193- 197.

37. '¥R eft 1ft l0i ~ ~, ~ tt.~.~. ~ ~~, ~ 3!7Wrr. 72 (3) (2001) 46-50.

38. ~ ~~, 0fl""llf?lCRl, ~ ~ Rcfl&;'PI'i ~~, \if,

&IT. ~ ~ ~ 28 (4) (2000) 3- 14.

39. ~ ~ vfi l0i ~ <11., ffl 409 (6822) (2000)

853-855.

40 . ~ 1ft~, CtJI'{tl'<I~01CtJ ~, m { ~ ~ m, ~ 31R 10i~, ffl 409 (6822) (2001) 850-852 .

41 . (>\T ~ 1ffl, '1 \'ts, <ri<T 1ffl l0i ~ T{! cct<B ~, ffl 409

(6822) (2001 ) 847-849.

42 . ~ 31R, ~ vfi l0i !fI'1 ~ 31R, ffl 409 (6822)

(2001) 832-833.

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174

43. ~3ffi' ~ ~, CfIOlI~I:!Cfil ~ eft 10i ~ ~~, ffl 409

(6822) (200 1) 829-31.

44. ~ t ~ ~ 10i ~ ~ t 10i ~ it~, ffl 409

(6822) ( ) 827-828.

45. CI'rct eft 10i ~ 3lR, ffl 409 (6822) ( ) 818-20.

46. ~ ~~, <f\JI"1 ~~, 1lT1ll~ ~ cB-~, ~ ~ ~, ffl 409 (6822) (2001 ) 834-835.

47. ~~, ffl 409 (6822) (2001) 758-760.

48. ~ it, ~3Rf ~ 31'rcB- c:T ~ ~ ~ ~ ~ ~A1C11c5~ I·{l, ~ ~ ~ ~ <:!'ret (1998).

49 . ~ cB-, ~ ~ 3ll~"iI~JJ~I"i .~ 3llRlf.1<:H ~ ~ ~4C'lqil'c, 5 (1995) 315.

50. cm31'r ~ 10'T, $~'<~~I'lC'l fW{, 3fTll> f//$c7C'lTV[), 96 (1985)

51.

51 . ~ ~ eft, ~ ~4C'lqik 4 (1994) 360-365.

52. ">ffi:r ~ it, ~ ~ 111c1Cfilctl ~ ~ JJ~re:CRl (~.~. .gCfilq'lct1 ~ 31'(1) \Jl16"iRlC1"1 ~~, ~,<:!'ret (1995).

53. fc)-wq, ~ ~, ~, ~ ~ ~fbT 1:!$.g~Cfi tffi. ~ ( 1994).