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Article: The molecular genetic analysis of hemophilia A: A directed search strategy for the detection of point mutations in the human factor VIII gene

TitleThe molecular genetic analysis of hemophilia A: A directed search strategy for the detection of point mutations in the human factor VIII gene
Authors
Issue Date1990
PublisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/
Citation
Blood, 1990, v. 76 n. 11, p. 2242-2248 How to Cite?
AbstractA directed-search strategy for point mutations in the factor VIII gene causing hemophilia A was used to screen eight potentially hypermutable CpG dinucleotides occurring at sites deemed to be of functional importance. Polymerase chain reaction-amplified DNA samples from 793 unrelated individuals with hemophilia A were screened by discriminant oligonucleotide hybridization. Point mutations were identified in 16 patients that were consistent with a model of 5-methylcytosine (5mC) deamination. Four new examples of recurrent mutation were demonstrated at the following codons: 336 (CGA → TGA), 372 (CGC → TGC), 372 (CGC → CAC), and 1689 (CGC → TGC). These are functionally important cleavage sites for either activated protein C or thrombin. Further novel C → T transitions were identified in the remaining arginine codons screened (-5, 427, 583, 795, and 1696), resulting in the creation of TGA termination codons. Differences in mutation frequency were found both within and between the CpG sites and between ethnic groups. These differences are assumed to be due to differences in the level of cytosine methylation at these sites, although direct evidence for this inference is lacking.
Persistent Identifierhttp://hdl.handle.net/10722/178484
ISSN
2015 Impact Factor: 11.841
2015 SCImago Journal Rankings: 6.395
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorPattinson, JKen_US
dc.contributor.authorMillar, DSen_US
dc.contributor.authorMcvey, JHen_US
dc.contributor.authorGrundy, CBen_US
dc.contributor.authorWieland, Ken_US
dc.contributor.authorMibashan, RSen_US
dc.contributor.authorMartinowitz, Uen_US
dc.contributor.authorTanUn, Ken_US
dc.contributor.authorVidaud, Men_US
dc.contributor.authorGoossens, Men_US
dc.contributor.authorSampietro, Men_US
dc.contributor.authorMannucci, PMen_US
dc.contributor.authorKrawczak, Men_US
dc.contributor.authorReiss, Jen_US
dc.contributor.authorZoll, Ben_US
dc.contributor.authorWhitmore, Den_US
dc.contributor.authorBowcock, Sen_US
dc.contributor.authorWensley, Ren_US
dc.contributor.authorAjani Et Al, Aen_US
dc.date.accessioned2012-12-19T09:47:58Z-
dc.date.available2012-12-19T09:47:58Z-
dc.date.issued1990en_US
dc.identifier.citationBlood, 1990, v. 76 n. 11, p. 2242-2248en_US
dc.identifier.issn0006-4971en_US
dc.identifier.urihttp://hdl.handle.net/10722/178484-
dc.description.abstractA directed-search strategy for point mutations in the factor VIII gene causing hemophilia A was used to screen eight potentially hypermutable CpG dinucleotides occurring at sites deemed to be of functional importance. Polymerase chain reaction-amplified DNA samples from 793 unrelated individuals with hemophilia A were screened by discriminant oligonucleotide hybridization. Point mutations were identified in 16 patients that were consistent with a model of 5-methylcytosine (5mC) deamination. Four new examples of recurrent mutation were demonstrated at the following codons: 336 (CGA → TGA), 372 (CGC → TGC), 372 (CGC → CAC), and 1689 (CGC → TGC). These are functionally important cleavage sites for either activated protein C or thrombin. Further novel C → T transitions were identified in the remaining arginine codons screened (-5, 427, 583, 795, and 1696), resulting in the creation of TGA termination codons. Differences in mutation frequency were found both within and between the CpG sites and between ethnic groups. These differences are assumed to be due to differences in the level of cytosine methylation at these sites, although direct evidence for this inference is lacking.en_US
dc.languageengen_US
dc.publisherAmerican Society of Hematology. The Journal's web site is located at http://bloodjournal.hematologylibrary.org/en_US
dc.relation.ispartofBlooden_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshChina - Ethnologyen_US
dc.subject.meshCodonen_US
dc.subject.meshDna - Geneticsen_US
dc.subject.meshEurope - Ethnologyen_US
dc.subject.meshFactor Viii - Geneticsen_US
dc.subject.meshHemophilia A - Ethnology - Geneticsen_US
dc.subject.meshHumansen_US
dc.subject.meshIndia - Ethnologyen_US
dc.subject.meshIsrael - Ethnologyen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshNucleic Acid Hybridizationen_US
dc.subject.meshPakistan - Ethnologyen_US
dc.subject.meshPolymerase Chain Reactionen_US
dc.subject.meshPolymorphism, Restriction Fragment Lengthen_US
dc.titleThe molecular genetic analysis of hemophilia A: A directed search strategy for the detection of point mutations in the human factor VIII geneen_US
dc.typeArticleen_US
dc.identifier.emailTanUn, K: kctanun@hkucc.hku.hken_US
dc.identifier.authorityTanUn, K=rp00787en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.pmid1979502-
dc.identifier.scopuseid_2-s2.0-0025202103en_US
dc.identifier.volume76en_US
dc.identifier.issue11en_US
dc.identifier.spage2242en_US
dc.identifier.epage2248en_US
dc.identifier.isiWOS:A1990EK72700012-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridPattinson, JK=6602087446en_US
dc.identifier.scopusauthoridMillar, DS=7102622556en_US
dc.identifier.scopusauthoridMcVey, JH=7005492040en_US
dc.identifier.scopusauthoridGrundy, CB=7004060712en_US
dc.identifier.scopusauthoridWieland, K=11541016400en_US
dc.identifier.scopusauthoridMibashan, RS=6603783353en_US
dc.identifier.scopusauthoridMartinowitz, U=16181345300en_US
dc.identifier.scopusauthoridTanUn, K=6602914262en_US
dc.identifier.scopusauthoridVidaud, M=7006897212en_US
dc.identifier.scopusauthoridGoossens, M=7101703913en_US
dc.identifier.scopusauthoridSampietro, M=7005694572en_US
dc.identifier.scopusauthoridMannucci, PM=36038519800en_US
dc.identifier.scopusauthoridKrawczak, M=7006351366en_US
dc.identifier.scopusauthoridReiss, J=7102782487en_US
dc.identifier.scopusauthoridZoll, B=7003841137en_US
dc.identifier.scopusauthoridWhitmore, D=7006106004en_US
dc.identifier.scopusauthoridBowcock, S=36884510200en_US
dc.identifier.scopusauthoridWensley, R=7003870003en_US
dc.identifier.scopusauthoridAjani et al, A=7003735774en_US

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