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Article: Family-based linkage disequilibrium mapping using SNP marker haplotypes: Application to a potential locus for schizophrenia at chromosome 22q11

TitleFamily-based linkage disequilibrium mapping using SNP marker haplotypes: Application to a potential locus for schizophrenia at chromosome 22q11
Authors
Issue Date2000
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mp
Citation
Molecular Psychiatry, 2000, v. 5 n. 1, p. 77-84 How to Cite?
AbstractFamily-based linkage disequilibrium mapping using SNP markers is expected to be a major route to the identification of susceptibility alleles for complex diseases. However there are a number of methodological issues yet to be resolved, including the handling of extended haplotype data and analysis of haplotype transmission in sib-pair or family trio samples. In the present study, we have analysed two dinucleotide repeat and six SNP markers at the COMT locus at chromosome 22q11, a region implicated in psychosis, for transmission distortion in 198 Chinese schizophrenic family trios. When individual markers were analysed using the TDT, two showed modest evidence of transmission distortion (186C/T, P = 0.04; Val158Met, P = 0.01). Using haplotypes of paired markers analysed by the program TRANSMIT, the most significant P value was 0.001, for the Met158Val and 900ins/delC polymorphisms in the COMT gene. The global P value for the haplotypes of all six SNP markers tested was 0.004, largely a result of the excess transmission of two extended haplotypes which differed at the marker 408C/G. The exclusion of this marker from the analysis gave a global P value of 0.002 and produced a five marker haplotype system which was significant at P = 0.0006. This haplotype consisted of the alleles -287G:186C:Val158:900insC:ARVCF930C, which may represent a background haplotype for the transmission of a schizophrenia susceptibility allele at chromosome 22q11. Our results support the hypotheses that either COMT is itself a susceptibility gene, or more likely that this region of chromosome 22 contains a susceptibility gene that is in linkage disequilibrium with COMT alleles.
Persistent Identifierhttp://hdl.handle.net/10722/175819
ISSN
2015 Impact Factor: 13.314
2015 SCImago Journal Rankings: 6.790
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Ten_US
dc.contributor.authorBall, Den_US
dc.contributor.authorZhao, Jen_US
dc.contributor.authorMurray, RMen_US
dc.contributor.authorLiu, Xen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorCollier, DAen_US
dc.date.accessioned2012-11-26T09:01:33Z-
dc.date.available2012-11-26T09:01:33Z-
dc.date.issued2000en_US
dc.identifier.citationMolecular Psychiatry, 2000, v. 5 n. 1, p. 77-84en_US
dc.identifier.issn1359-4184en_US
dc.identifier.urihttp://hdl.handle.net/10722/175819-
dc.description.abstractFamily-based linkage disequilibrium mapping using SNP markers is expected to be a major route to the identification of susceptibility alleles for complex diseases. However there are a number of methodological issues yet to be resolved, including the handling of extended haplotype data and analysis of haplotype transmission in sib-pair or family trio samples. In the present study, we have analysed two dinucleotide repeat and six SNP markers at the COMT locus at chromosome 22q11, a region implicated in psychosis, for transmission distortion in 198 Chinese schizophrenic family trios. When individual markers were analysed using the TDT, two showed modest evidence of transmission distortion (186C/T, P = 0.04; Val158Met, P = 0.01). Using haplotypes of paired markers analysed by the program TRANSMIT, the most significant P value was 0.001, for the Met158Val and 900ins/delC polymorphisms in the COMT gene. The global P value for the haplotypes of all six SNP markers tested was 0.004, largely a result of the excess transmission of two extended haplotypes which differed at the marker 408C/G. The exclusion of this marker from the analysis gave a global P value of 0.002 and produced a five marker haplotype system which was significant at P = 0.0006. This haplotype consisted of the alleles -287G:186C:Val158:900insC:ARVCF930C, which may represent a background haplotype for the transmission of a schizophrenia susceptibility allele at chromosome 22q11. Our results support the hypotheses that either COMT is itself a susceptibility gene, or more likely that this region of chromosome 22 contains a susceptibility gene that is in linkage disequilibrium with COMT alleles.en_US
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/mpen_US
dc.relation.ispartofMolecular Psychiatryen_US
dc.subject.meshAdolescenten_US
dc.subject.meshAdulten_US
dc.subject.meshAllelesen_US
dc.subject.meshAsian Continental Ancestry Group - Geneticsen_US
dc.subject.meshChromosome Mappingen_US
dc.subject.meshChromosomes, Human, Pair 22en_US
dc.subject.meshDna Primersen_US
dc.subject.meshDna, Satellite - Analysisen_US
dc.subject.meshFamily Healthen_US
dc.subject.meshFemaleen_US
dc.subject.meshGenetic Markersen_US
dc.subject.meshGenetic Predisposition To Diseaseen_US
dc.subject.meshHaplotypesen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibriumen_US
dc.subject.meshMaleen_US
dc.subject.meshMiddle Ageden_US
dc.subject.meshPolymorphism, Single-Stranded Conformationalen_US
dc.subject.meshSchizophrenia - Geneticsen_US
dc.titleFamily-based linkage disequilibrium mapping using SNP marker haplotypes: Application to a potential locus for schizophrenia at chromosome 22q11en_US
dc.typeArticleen_US
dc.identifier.emailSham, PC: pcsham@hku.hken_US
dc.identifier.authoritySham, PC=rp00459en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1038/sj.mp.4000638-
dc.identifier.pmid10673772-
dc.identifier.scopuseid_2-s2.0-0033966919en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033966919&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume5en_US
dc.identifier.issue1en_US
dc.identifier.spage77en_US
dc.identifier.epage84en_US
dc.identifier.isiWOS:000085165600015-
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridLi, T=36072008200en_US
dc.identifier.scopusauthoridBall, D=7202703810en_US
dc.identifier.scopusauthoridZhao, J=7410311266en_US
dc.identifier.scopusauthoridMurray, RM=35406239400en_US
dc.identifier.scopusauthoridLiu, X=7409286408en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridCollier, DA=26642980600en_US

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