priorCysticFibrosis

priorCysticFibrosis - CF is the most common lethal...

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Unformatted text preview: CF is the most common lethal autosomal recessive disease among Caucasians, with an incidence of a characterized by insulliciency. bout 1 in 2,500 births in the United States. The defect is chronic obstructive pulmonary disease and pancreatic exocrine DIAGNOSTIC CRITERIA 1. Elevated sweat chloride ( >99% of pattentst AND ElTl-ER 2. CI'II‘OI'IIC WINCH“ disease teventally, >99% of patlents; may be absent at time of D!) 3. Pancreatlc lnsufflclency (80-90% of patlentst The CF gene has recently been cloned and the mutation responsible iorthe disease on approximately 75% of the atlected chromosomes has been shown to be a three base pair deletion. which results in the deletion of a single phenlyalanine residue at position 508 of the cystic fibrosis transmembrane regulator protein (Cl-TR]. The CF deletion is reterred to as AF 508. EXONS #234563607 DOMAINS 3. Protein model membranasoannlng nucleotide rangaroyle) membrane spannrng nucleotide orndrng told binding told CHO Memorane -COOH I211 sun: I l ‘5 WIN! I! iullbIS I‘lhfibid 19 HUM”?! SLII‘IIIfIIIDDEIDIIIIIIIIFfIEIIICIDIIJLII IIIIIIIIII IIII II|II||I|II I I II III! ||I||- l l l AA UDIEIM _ IIIIII I IIIIII II III I II |IIIIIl| IIIIIII ||I IIIII III III III II IIIIIII I III I | I I I I I III ISP'Ww III I III I I I I I IIIIIIIIIIIIII IIIII IIIIIIIIIIIIIIIIIIIIIIIIIIIII III III III II I “3‘3" 0 7 WW Tmcmo zooennaqeriamcurqn LDH'Jon Lvo'i Hammer MiIEI’i Jerusaiem IIII II] II] I::IIIU III III :I Membrane spanning AT? binding l'HIonmln Mcmbmn: apanntng ATP blndlng I: WIEEZK - WIN GA :1 Oh“ I: Urm‘m" I‘JU m qth cocoa Table 2. Comparison of Matched Pairs with the Genotypes Ft117H/AF508 and AFm’AFm.* No. or VARIABLE PAIRS Garcon»: DIFFERENCE P VALUE AW Congenital Bilateral Absence AF“; ARM of the Vas Deterens Age (yr) 23 23539.6 23.1:9.0 0.4210 0.4 Age at diagnosis 23 “12:10.5 25:43 13:10.9 0,002+ A Primarily Genital F0rm of Cystic Fibrosis sweat Chloride I7 80:18 '08: I4 _28=24 <0‘mII Arturo Anguianc. MD. Robert D Oates. MD JeanA A'nos. PhD. Michael Dean. PhQ Bernard Gerrard; Ciaudia Stewart. Immomuen Thomas A. Matter: Marga it. 'the. PhD Aubrey Mrlunsw MB.BCn. DSc. FRCP. DCH FEVI (‘7: ofpredtctcd) 22 73:22 69:23 35:26 0.5 Shwachman clinical IS 84: t] 77:14 6.7214 0.07 score“ Pancreatic sufficiency 23 20 l — «1001; (no. of patients) Restriction-enzyme recognition site PCR primer created by mutation I 4 V Agarose gel Mutatign Dgtggtign Known Disease Mutations New Mutations > yaw-mam W47" I 8350 8360 3370 — CA CCTCTTTACA GTGAAATGCCC c— I T GGAGAMYGT ucrmcesa o— Wild-Type Seq ueice Mulart Sequence 1 GGAGMATGT CACTTTACGGG G WHd-Iype pr mer Dovmslream primer +—.—._.. _i— mm ‘ ATCGBICACIEEAATDG --9 J- ATCGGTCACTGCAATCT «9 +- TAGCCAETGAEG‘ITAEE TAGGCLAGTGFCGTTAGK Pam Chain Reach Mulanl primer _ fl , ArmstcAcmmTcT I» No pcn ‘— ATCGGTCACTGEAmG fl No PCR *— TAGUCA'GTGA’JGmGC TKG'CCKGTGACGTTAGA ACCGGC WT HET NUT Norma) _ mecca 1 C "”‘ - - - _ 60066 W csccca Neel WT MUT WT MUT WT MUT 2 3 Hill I,“ l i 5‘ CTTTTCCTCCATTATGCCTGGCACCATTMAGMMTMCMCTTTUETCrtrCETATaATEMTATACAracncncccrmrcmcurccm: 1' 3' EAMAGGACCTAATACCCAECGTGGTMTTHI'TTTATAGTAGMACCRCAMGGATACTACTTATATCTHTGTCTTCECACIACTTTEE-IACGCHE 5' EH! 1' CTTI’MTAGTAGAHCCAC '3' CF-M‘SOB 'i' TTCTTTTATACTMCEACM 5' Fl; l-Sequum of FCR-nmplifled mien of CF gene, with numbering of Riordan ct Il.’ Primcr scqumccs are underlined and [hm nucleotides deleted in riiFWI mutation are highlighted. Probe CF-N and CF-A F“ are also Show. Allele Specific Oligonucleotide (A30) for the Sickle Cell Mutation BA [3“ 13A [35 BS [35 O. O T Hybridization TG AC1" CCT GAG GAG AAG TC BA ASO CAC Cl'G ACT CCT GAG GAG AAG TCT GCC----- Normal CAC CTG ACT CCT GTG GAG AAG TCT GCC----- Mutant A F TG ACI' CCT GTG GAGAAGTC BS ASO l Hybridization Q. 0 BA [3" [3"[35 [55135 wild-type PRIMEBfi swam: DNA Blow —|:| QM tar 1:? 3‘0le + N§ “RE: l m 510le : N —— N AF 47M %_,—i BIOTW HYEFHDIZE TO NITHOCELLULOSE STRIP 185delAG EEOV'IN BIOTJN — MUTANT CLwGDNUC,ECT\DE . NDFWIA. DLIGDNUOLEOY‘DE [DEVELOP 3&1 CAFIFliEFK OF AF MUTATION C + _ _ _ 08 542 551 553 1303 Cnnlmi AFQA Gé‘fl Géfixn nfix n K «mafia 542 551 553 1303 Conltol G I I) D R K N K 10% 11 2% 5‘2 551 553 1303 Conlroi a.x vino n'x n x wfiugm 542 551 55: 1303 Conlrol a x a D FL! :1 K 1o§1u§21 .— _ .— .— _ m. _. ...... — u— — — HinHflll‘l I'- h'" “V —- 131RWI+1G>T .— — m _. 15:n.?|l+lfi'.\T n _ ._ —- _ 'n P E .— -.,. __ a, _ y a _. m a .. _ b a. 1 l Id .. . ’ a - a 1’ g 3 .. _ u _ _ .MHHM 8 ‘- - rum: minnow — — — — _u:1?mq+fia}4 m .. .— .._. _ —"* 5 l5; 11.?‘70+1D,‘} a — .— _ _ :7:er n2): Eh .— _ _. _ _ __ _ a Ififimdal" —" "'- “" — —52: mnan ‘- MUCH fl'rVJl'IHA — — W - —5-l:erhL'GK —EETPIL-w-r’. m um um 1c'ml pen: I \n um m nihith 9 ID If LT amuwumlmuu l: r: a g 2 a. 1: 2 § E a E g I E g “gm-91:leydmloyduubu 5 5 SJ 5 1; ‘mRAYpmelL i a a = = c 3 q n E E t ...
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This note was uploaded on 07/17/2008 for the course EEOB 733 taught by Professor Burghes during the Spring '05 term at Ohio State.

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priorCysticFibrosis - CF is the most common lethal...

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