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Ann Hum Genet. 2008 Mar;72(Pt 2):279-87. Epub 2007 Dec 18.

Shared genomic segment analysis. Mapping disease predisposition genes in extended pedigrees using SNP genotype assays.

Author information

  • 1Department of Biomedical Informatics, University of Utah, 391 Chipeta Way, Salt Lake City, UT 84108, USA. alun@genepi.med.utah.edu

Abstract

We examine the utility of high density genotype assays for predisposition gene localization using extended pedigrees. Results for the distribution of the number and length of genomic segments shared identical by descent among relatives previously derived in the context of genomic mismatch scanning are reviewed in the context of dense single nucleotide polymorphism maps. We use long runs of loci at which cases share a common allele identically by state to localize hypothesized predisposition genes. The distribution of such runs under the hypothesis of no genetic effect is evaluated by simulation. Methods are illustrated by analysis of an extended prostate cancer pedigree previously reported to show significant linkage to chromosome 1p23. Our analysis establishes that runs of simple single locus statistics can be powerful, tractable and robust for finding DNA shared between relatives, and that extended pedigrees offer powerful designs for gene detection based on these statistics.

PMID:
18093282
[PubMed - indexed for MEDLINE]
PMCID:
PMC2964273
Free PMC Article

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