q, s 3- J €=P o o o gs+ o q, (v (, E o g '3E81() E s q, q, o q, {- s s s 'E _lt t- qto gt J {- rO3 (, = 9E r- q, J rF o N L) FE8 $s I .eSE qt 6o- -s s F oq, o.'e€o -t 5E=cn EL' qr 3i €eEi 6 i? H* i.-E' I Ei E E Es E tsis E i I g t F E s ,RE is.g< *U p =e E iF*6 3 H+ gllt =PE €€t'E in* t E t E+5 EE ES s € + E =s,.i'. Efu!Iul* lt !l tuii i' O -,' l'\ uV 'b s'' \ U ( T' Eo o o \) q, L \Fo q, 6 +x a, F 3- oJ ctl €re'a o .Y o:*l: o.9 /tannv Qrk H"". 7fu" €aao,rec n!cdh]r6'rngn'odalsl&fuB' d..rodrerE!! @pFo! h el d rrtrlt€d hdsd sor* \ I I I Oi,,n (7 E*ryodcc4l. hd@ ts dooer4hs, My 93nt cdldgdt€d€€ €€ Bly iddt d h bn io h@ odwd h ttdEl els o€r-g 6tr6u* dlqr lo pEn c* r! drds nE c.a€l sd tu ctrblp5.ra Ar*Er cd8cc.ttd! 6lttrb.. *rictr e .1./a<z€a 4 4 14 / 7acqa^r a2/a.t o. 0, \, o t{- o .t-o 3-o o- .t- g q, o,3- r|Fs d s vl q, E o sql (D o 3 F q, g o q, o g q, T: o -g F ct ll 7(. 4r'"./ce -*.! Qnne.t a)14 i ASL" ft-ts P&<adrk ,?r'Ja, 1,2 ltl tz*3 ?gu 6aqq? J2 6eaet 2y /lfaa,- l<ict €ti.c3i, 4'QS'eve-4'c f,4" 'va</<as-P<,ht i A,vA/6* ui++ (t 11161y31t.Er ft**l . l|.! ir ||ld@ k Erdo..d by. ocl,L |{.nLir ItE rudd sdopo grdo Lp €r lrc nEnbr€nd, tu holu, d!€.rlsrlna, dldarddpo.erscd||M adlBolslel Mld Ih€ porB rs t€ eslEiiayslnEr4h *ltdr ool4aE lilro tE ctloddsh dnt nls n.h6 and gorEtc ndeid (mF|{A erb uts ru6! anotF q'rotEm, ibnsrBhd€0€fud€.'dldoog,|l hMB *,rh dmmn' drd r'ot omd !r dm@a ro s .n i b drd'sd fprc 10.6 a Hulrl x rrnoTYtE. Th. ildieidul di|t,]|{'l@ dnr d]f l+ tlE 2, f.in diE rid.ly i'r 14 .!d i! 6!r|rE F ddh I' dljr pr.p.ndd! .h. drM llG bcn {'GdEqlt dii.d @ nd-E dft@ ir dEn ohlEild ud b dlri.3ljri tid dady 6m @ .r.dE, Ndi6 dii ndh.tr of ..tFm D& m Ery rinilrtd n . i.Lditl. 4t t?<qte 6<.r.*"., ta.z lo t?-< t'< balX i Ctao,1*. *< /ti,'a3t { Qttr,lT - Are aa-rr ,?r/o."4-ra-; /aa.v- Qoo/<r; + 44<q/+ 6an ..a fgure 4.17 MTTOCrtONDnlA. Thc inne. n€mbrone of a nimchondrion is shapedinto folds 6lled itrcr$c th€ su.hcc ate! for oxid.tivc mehboli'm. crosssectlonltrocul micaogliph. tr n I E E tr Opte ltye,<(t I T.eot<.,;Li A t.sl- ll,to eh"lol Fi3!E'6' C.6IrhlonBr!.dbrdrLlDNi{ft.rrx !!BrEIndrsedbyrh.m.k!6 fat*c,it . tu.ddtynlotlhFc!tx^4lddadtalh.lolid.rd!n*.nndn rtd6hlhr n rod..dnd DnA.E hdd.n by ol.r.ordlll b rt. k r.r rli urtsr ldr rh. rmd.u lor rn.r<rrrdo' or rh. h.ry.nd urhr m.& tcNn ry o, x-c. L.M.nd a. aan4.1P4kwol.ffi6 2t- t.t cwtlt tt rtby T' at {- 3- q, -gs H q, g ]n a, q, (D C' >.-> L T's EE o Fg -s o (, .l< o .t-o F€ = olr ,/a/ .!/ru<flapaRtaZ ce^/ a€e2 fa "fdQa* ,.tJe+eqz 6a/e/c oti*art Tabh16.r Fhcnotyp€3.53ocletcd*hh romc mitochondtlal nut dorE Nucl.otlde Mltociondrl.l chrigld conponad.ffi th.idrp.l 3460 NDlofconpler lb LHON 11778 ND4ofGmpler I LHON 11184 NDB ofcomglcr I LHON ESS NARP 3243 MEU5,pEo 1211 MEI.AS 32gl MEIAS 3251 PEO 32fi PIO 58S2 Pto 't03 !814 fiitAct' Enclph.loprdrr E344 MIRNF 8356 MERRI gSC' O'dlo'|lFFthy r0006 NNAC' PIO t2245 PEO t4?09 rRNAotr Myoprth, 15023 htrl infrnlihnMllttitcn dliordlr r5990 Myop.tht tLHoN ttb./s her.dit ry optic n.uroprth, NARPN.uot..ic murcj. s.l,cts, .t tr., atlahls PE|mtot$ MERRF ratodonlc .pil.?.t ..d n$.d.Ed frb.r 3tndrom.; MELA Mitodo.di.l &roPathy. .iaPhaloP.thy, l.dic .cido5i5, itrokclih .P|rod6; PEOPrcgtestive *t€m.l oPhihtldoPl.gh lConola | 6 NAOH d.hrdrcr.na3., Comolq v i5 AtP synth*c. .lnrRilahrru4.ih. n r;nd;for€ith€rA;rc: in tRNAsi'lrcn.th.Y rtandrfo'.inq T o' c. ,lK A tVtra<,?aorp Rt)2. l€Fecn //16€4/ z€/t ? Figur€r5.2 Inhcrltanceol myoclonlcepllep5y wirh raSg€d-rcdRber ditcas€ {MERRI} In humant.{A) Elecrcnmicrograph olan abnormalMERRFmltochordrioncontainhS Daracrvsbllineinclusions. 18 )Th€ pedigree ;hows inheritanceof MIRRF in one famllv and rhepercenkSe of thc r lochondrlalneach Dcrso!found lo bewildtvpe or mulani iMicro6aDhcounesy ol D. C.wallace,Irom J. i"1.sho-ffnlr, M. T. L;t, A. M. s. l,ezza,P. sclbcl, S.w. B6ulngerand D. C.Wall6ce. 1990. Crr 6l: 93r.1 u 15 10 100 100 100 94 94 93 97 96 96 E5 90 Rflf, Cr,v 3e er€o 7a zOtat ftr/ auO../.O Ails' 4f *a, tBl Mitochondrial DNA patt€m lor lndlviduals lndicatedln bluc o o ,1,,{ DNA 4.6 kb II I I 4,5kb I 4,1tb III I I I I All thc prog€nyof a pantcular f€m6lc Y 1.3kb hav. the !ah. patt€m of mitochon&ial Stn€llor DNA bandsas in the moiher, DNA 0.4kb Figurer5.r MalernaI inherilanceofhuman mitochondrialDNA. (A) PauemoIDNA lragments obtaincdwhen mirochondnalDNAis digesredwith ih€ restndlon enzym€pdell. Thc DNA typ€ at rhe leh includcs. fragmenlof3.6kb (r€d).TheDNA typ€ at the righr contalnsacleavage rit€ lor flaell within rhc 8.6-kb fragment,which resuksin srnall€rfragm€nrs of4.5 kb and 4.1 kb (blue). (A) Ped'8recshowinS marernal inheriranc€ ofrhe DNApanem with lhe 8.6-kbfragment(red symbok).Thc mirochondrialDNA rype* lransmhredonly ftrough rhe morhcr. [A[t€rD. C. Wallace. l9a9. Trehdtin Ceaetict5t 9.1 .12af /<? .itqr t!tla,e4.n7-r4 /R? tyan2on .e46 /a0€<t7eo // 73F ,/auap dE,va,yg: ,/ar 6ae,u ra-VarA.")1 I -_..__ 71. 4atrt4a'n u 4..r1"&.q" ti<oJtcrri<oJtcr I LodLL.l .ur.eEqtd."r rrid- Pdt-t -d@belfttuflork@imes rtn ntbrd4q TUESDAy,IUNA n, 2&0 oNa Do[r ticCodcofHuman,Ii bIs CrachedbySeientist ASIIARID SlJfrI ? Rivsls'Anmunccfi! iiarts t{srYiledicr tua,Risb md All t nomrt rarra eyl|s$hM!dl.l.l|u! ..i.'dnfuhr.d!, ar. d br drdS ftrr!Fdi-&Ill 0r rLr rr rd..d h r tuq-rdE-Du ?u/t,i h^a * e f'zer O/rrz.<€a.T 9e.47 ea.r&t - (o5t' ft. titlE /<*l*r (aa1'et14 hq/b./ lab 2llerr r 7.t< leJ\--g Vlhat was the the Human GenomeProject's budget? U.S. Euman GenomeProject Funding ($Millions) FY NIHI U.S.Total 1988 10.7 t7.2 27.9 1989 18.5 28.2 4.7 ---- 1990 27.2 59.5 P=l t99l 47.4 s14 134.8 1942 59.4 104.8 164.2 1993 63.0 t06.1 169.1 1994 OJ.J 127.4 190.3 1995 68.7 153.8 222.5 1996 73.9 169.3 243.2 199,7 77.9 188.9 266'8 1998 85.5 2r8.3 303.8 Thesenumbers do not include consbuctionfunds, which arp a very small part of z<,r,uoz a?2 2<'re/J? *c1 fe?4*w<,,*< OwZ| /, 3//4cc &aceoan aF 7?€ 6 6.ota24. 4.r'tcaac /*ZfQ_ Frequency(%) Description l,t Tr.nshtedpotions of the 2t,000 scncs dttered aboutth. .hrnmnmm.s t4 NoncodingDNA thd constiNte,$e gred mriority of erchhunrn s€nc 5 Regionsofthe senonethat hrve becn dupliorcd 2 S€qnen€eth$ h$ chmcrcristis ofa scnebut isnot, frnctjonil sene ?0 Constltutivehctcrochromrtin, localized ned cendoheresand telonrcr€s J SrureringrcpsB ofr f€w nucleotidssnch s CGG, tepeatedthousnds ofnn6 4' 2I%: LonginrcEpeEedelemenB(LINrE,'hichrerctive@nsPosons I I %: Shoft intesp*sd el€nenc (SINES),which rc 'ctiv€ @NPosons 8%, RetrotrinspoioN,which coit in longt.nnind repeiE(LTR' d crch end t%: DNA tmnsposonfo$ih 7E ,laaet adt wE t?At O.A fe? 4ocd, ?*eatl aqrce It Oc4 .t lct ca)-.1 /tt zr ,t ' E LINES E SINES Ef LTRS 9.1 A huixn Lryotyp. corulrB of t6 chronosom.l A karlotyp€for a m.h b $*n hel€;a k ryotyp. tor a femalewould havetwo X chloinosoffi //sMlPnobt.t€./ Table20.6 Ave6gecharaderistics of genes in the humangenome ,?ttqae 4.1 leE (aata 347 8.8 ntr/j, Slzeof intemal.xon 145bp Sizeof intron 3,365bp 5lz. of 5' u r.nslat€dr€gion 300bp Sizeof 3' unirdnslatedrcgion 77Obp Sizeof codlnSltgion l,l4Obp 'rotal lengthof Sene 27,000bp q, g a, E o sq, (D s C' E J I ql -s + s oql sU qt q, s(, q= q, o o .t- sq, o ql z g .v,o a .J o- i: o oll -t ,. 4e HArVlv 6:Et/a.tE la.vzityt ,ftrwt,e -<a?/ arn ,?crtrinira tt:/ra€.;g'.a:r- ./.r^ Zn za+rpil loan, kl a z(<^ -Noocodig t6gm€ a osrwofi genG Conlsadv€t rogarbd ! a€qllonc€o / ngurr 7,t Oc.uEtnc.o{ dlfu hndr of un$l.