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Article: The trimmed-haplotype test for linkage disequilibrium

TitleThe trimmed-haplotype test for linkage disequilibrium
Authors
Issue Date2000
PublisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/
Citation
American Journal Of Human Genetics, 2000, v. 66 n. 3, p. 1062-1075 How to Cite?
AbstractSingle-marker linkage-disequilibrium (LD) methods cannot fully describe disequilibrium in an entire chromosomal region surrounding a disease allele. With the advent of myriad tightly linked microsatellite markers, we have an opportunity to extend LD analysis from single markers to multiple-marker haplotypes. Haplotype analysis has increased statistical power to disclose the presence of a disease locus in situations where it correctly reflects the historical process involved. For maximum efficiency, evidence of LD ought to come not just from a single haplotype, which may well be rare, but in addition from many similar haplotypes that could have descended from the same ancestral founder but have been trimmed in succeeding generations. We present such an analysis, called the 'trimmed-haplotype method.' We focus on chromosomal regions that are small enough that disequilibrium in significant portions of them may have been preserved in some pedigrees and yet that contain enough markers to minimize coincidental occurrence of the haplotype in the absence of a disease allele: perhaps regions 1-2 cM in length. In general, we could have no idea what haplotype an ancestral founder carried generations ago, nor do we usually have a precise chromosomal location for the disease-susceptibility locus. Therefore, we must search through all possible haplotypes surrounding multiple locations. Since such repeated testing obliterates the sampling distribution of the test, we employ bootstrap methods to calculate significance levels. Trimmed-haplotype analysis is performed on family data in which genotypes have been assembled into haplotypes. It can be applied either to conventional parent-affected- offspring triads or to multiplex pedigrees. We present a method for summarizing the LD evidence, in any pedigree, that can be employed in trimmed-haplotype analysis as well as in other methods.
Persistent Identifierhttp://hdl.handle.net/10722/175816
ISSN
2015 Impact Factor: 10.794
2015 SCImago Journal Rankings: 8.769
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorMaclean, CJen_US
dc.contributor.authorMartin, RBen_US
dc.contributor.authorSham, PCen_US
dc.contributor.authorWang, Hen_US
dc.contributor.authorStraub, REen_US
dc.contributor.authorKendler, KSen_US
dc.date.accessioned2012-11-26T09:01:32Z-
dc.date.available2012-11-26T09:01:32Z-
dc.date.issued2000en_US
dc.identifier.citationAmerican Journal Of Human Genetics, 2000, v. 66 n. 3, p. 1062-1075en_US
dc.identifier.issn0002-9297en_US
dc.identifier.urihttp://hdl.handle.net/10722/175816-
dc.description.abstractSingle-marker linkage-disequilibrium (LD) methods cannot fully describe disequilibrium in an entire chromosomal region surrounding a disease allele. With the advent of myriad tightly linked microsatellite markers, we have an opportunity to extend LD analysis from single markers to multiple-marker haplotypes. Haplotype analysis has increased statistical power to disclose the presence of a disease locus in situations where it correctly reflects the historical process involved. For maximum efficiency, evidence of LD ought to come not just from a single haplotype, which may well be rare, but in addition from many similar haplotypes that could have descended from the same ancestral founder but have been trimmed in succeeding generations. We present such an analysis, called the 'trimmed-haplotype method.' We focus on chromosomal regions that are small enough that disequilibrium in significant portions of them may have been preserved in some pedigrees and yet that contain enough markers to minimize coincidental occurrence of the haplotype in the absence of a disease allele: perhaps regions 1-2 cM in length. In general, we could have no idea what haplotype an ancestral founder carried generations ago, nor do we usually have a precise chromosomal location for the disease-susceptibility locus. Therefore, we must search through all possible haplotypes surrounding multiple locations. Since such repeated testing obliterates the sampling distribution of the test, we employ bootstrap methods to calculate significance levels. Trimmed-haplotype analysis is performed on family data in which genotypes have been assembled into haplotypes. It can be applied either to conventional parent-affected- offspring triads or to multiplex pedigrees. We present a method for summarizing the LD evidence, in any pedigree, that can be employed in trimmed-haplotype analysis as well as in other methods.en_US
dc.languageengen_US
dc.publisherCell Press. The Journal's web site is located at http://www.cell.com/AJHG/en_US
dc.relation.ispartofAmerican Journal of Human Geneticsen_US
dc.subject.meshAllelesen_US
dc.subject.meshChromosome Mapping - Methods - Statistics & Numerical Dataen_US
dc.subject.meshChromosomes, Human - Geneticsen_US
dc.subject.meshFemaleen_US
dc.subject.meshGene Frequency - Geneticsen_US
dc.subject.meshGenetic Diseases, Inborn - Geneticsen_US
dc.subject.meshGenetic Heterogeneityen_US
dc.subject.meshGenetic Markers - Geneticsen_US
dc.subject.meshGenetic Predisposition To Disease - Geneticsen_US
dc.subject.meshHaplotypes - Geneticsen_US
dc.subject.meshHomozygoteen_US
dc.subject.meshHumansen_US
dc.subject.meshLinkage Disequilibrium - Geneticsen_US
dc.subject.meshMaleen_US
dc.subject.meshModels, Geneticen_US
dc.subject.meshMutation - Geneticsen_US
dc.subject.meshPedigreeen_US
dc.subject.meshProbabilityen_US
dc.subject.meshRecombination, Genetic - Geneticsen_US
dc.subject.meshSoftwareen_US
dc.titleThe trimmed-haplotype test for linkage disequilibriumen_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.doi10.1086/302796en_US
dc.identifier.pmid10712218-
dc.identifier.scopuseid_2-s2.0-0033927950en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0033927950&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume66en_US
dc.identifier.issue3en_US
dc.identifier.spage1062en_US
dc.identifier.epage1075en_US
dc.identifier.isiWOS:000088373200026-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridMacLean, CJ=7102972772en_US
dc.identifier.scopusauthoridMartin, RB=7501381656en_US
dc.identifier.scopusauthoridSham, PC=34573429300en_US
dc.identifier.scopusauthoridWang, H=7501743683en_US
dc.identifier.scopusauthoridStraub, RE=7203034348en_US
dc.identifier.scopusauthoridKendler, KS=35396760800en_US

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