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Article: A genome-wide scan in forty large pedigrees with multiple sclerosis

TitleA genome-wide scan in forty large pedigrees with multiple sclerosis
Authors
Issue Date2007
PublisherSpringer Japan. The Journal's web site is located at http://link.springer.de/link/service/journals/10038/index.htm
Citation
Journal Of Human Genetics, 2007, v. 52 n. 12, p. 955-962 How to Cite?
AbstractThe epidemiology of multiple sclerosis suggests that a complex interaction of genes and environment contribute to susceptibility. To enrich for families with large genetic effects and to potentially reduce genetic heterogeneity, we screened a sample of 18,794 probands and identified forty families with four or more affected individuals. Within these 40 families, HLA DRB1*15 was present in 70% of affected individuals; the transmission disequilibrium test showed a significant excess in transmission of DRB1*15 alleles to affected individuals (47 transmitted, 19 untransmitted, χ 2 = 11.9, p = 0.00057). A 10 cM genome scan was performed and analyzed for linkage under a parametric model with heterogeneity. No excess of significant sharing was observed (HLOD > 3.3) in the parametric multipoint analysis. No region exceeded that for marker GATA8A05 with an HLOD = 1.11. Follow-up genotyping with 17 microsatellites revealed a significant two-point parametric HLOD = 3.99 at marker D4S1597. Transmission disequilibrium tests for markers in this candidate region showed no transmission distortion. A scan for variants in a gene adjacent to D4S1597, PALLD, was negative for synonymous or nonsynonymous changes. A final multipoint scan incorporating all microsatellites in the region provided an HLOD = 1.30. The inability to find significant linkage in these highly penetrant families suggests that linkage is not the optimal tool for dissecting the inheritance of MS. © 2007 The Japan Society of Human Genetics and Springer.
Persistent Identifierhttp://hdl.handle.net/10722/81469
ISSN
2015 Impact Factor: 2.487
2015 SCImago Journal Rankings: 1.416
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorWiller, CJen_HK
dc.contributor.authorDyment, DAen_HK
dc.contributor.authorCherny, Sen_HK
dc.contributor.authorRamagopalan, SVen_HK
dc.contributor.authorHerrera, BMen_HK
dc.contributor.authorMorrison, KMEen_HK
dc.contributor.authorSadovnick, ADen_HK
dc.contributor.authorRisch, NJen_HK
dc.contributor.authorEbers, GCen_HK
dc.date.accessioned2010-09-06T08:18:08Z-
dc.date.available2010-09-06T08:18:08Z-
dc.date.issued2007en_HK
dc.identifier.citationJournal Of Human Genetics, 2007, v. 52 n. 12, p. 955-962en_HK
dc.identifier.issn1434-5161en_HK
dc.identifier.urihttp://hdl.handle.net/10722/81469-
dc.description.abstractThe epidemiology of multiple sclerosis suggests that a complex interaction of genes and environment contribute to susceptibility. To enrich for families with large genetic effects and to potentially reduce genetic heterogeneity, we screened a sample of 18,794 probands and identified forty families with four or more affected individuals. Within these 40 families, HLA DRB1*15 was present in 70% of affected individuals; the transmission disequilibrium test showed a significant excess in transmission of DRB1*15 alleles to affected individuals (47 transmitted, 19 untransmitted, χ 2 = 11.9, p = 0.00057). A 10 cM genome scan was performed and analyzed for linkage under a parametric model with heterogeneity. No excess of significant sharing was observed (HLOD > 3.3) in the parametric multipoint analysis. No region exceeded that for marker GATA8A05 with an HLOD = 1.11. Follow-up genotyping with 17 microsatellites revealed a significant two-point parametric HLOD = 3.99 at marker D4S1597. Transmission disequilibrium tests for markers in this candidate region showed no transmission distortion. A scan for variants in a gene adjacent to D4S1597, PALLD, was negative for synonymous or nonsynonymous changes. A final multipoint scan incorporating all microsatellites in the region provided an HLOD = 1.30. The inability to find significant linkage in these highly penetrant families suggests that linkage is not the optimal tool for dissecting the inheritance of MS. © 2007 The Japan Society of Human Genetics and Springer.en_HK
dc.languageengen_HK
dc.publisherSpringer Japan. The Journal's web site is located at http://link.springer.de/link/service/journals/10038/index.htmen_HK
dc.relation.ispartofJournal of Human Geneticsen_HK
dc.rightsThe original publication is available at www.springerlink.com-
dc.subject.meshGenetic Predisposition to Disease-
dc.subject.meshGenome, Human - genetics-
dc.subject.meshHLA-DR Antigens - genetics-
dc.subject.meshMultiple Sclerosis - epidemiology - genetics-
dc.subject.meshPedigree-
dc.titleA genome-wide scan in forty large pedigrees with multiple sclerosisen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=1434-5161&volume=52&issue=12&spage=955&epage=962&date=2007&atitle=A+genome-wide+scan+in+forty+large+pedigrees+with+multiple+sclerosisen_HK
dc.identifier.emailCherny, S: cherny@hku.hken_HK
dc.identifier.authorityCherny, S=rp00232en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s10038-007-0194-6en_HK
dc.identifier.pmid18000641en_HK
dc.identifier.scopuseid_2-s2.0-36448943599en_HK
dc.identifier.hkuros139328en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-36448943599&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume52en_HK
dc.identifier.issue12en_HK
dc.identifier.spage955en_HK
dc.identifier.epage962en_HK
dc.identifier.isiWOS:000251157700001-
dc.publisher.placeJapanen_HK
dc.identifier.scopusauthoridWiller, CJ=6602404452en_HK
dc.identifier.scopusauthoridDyment, DA=6603145913en_HK
dc.identifier.scopusauthoridCherny, S=7004670001en_HK
dc.identifier.scopusauthoridRamagopalan, SV=14049256200en_HK
dc.identifier.scopusauthoridHerrera, BM=8859807100en_HK
dc.identifier.scopusauthoridMorrison, KME=14629077800en_HK
dc.identifier.scopusauthoridSadovnick, AD=7005523120en_HK
dc.identifier.scopusauthoridRisch, NJ=16939783400en_HK
dc.identifier.scopusauthoridEbers, GC=15219142200en_HK

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