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

Ann Hum Genet. 2008 Mar;72(Pt 2):279-87. doi: 10.1111/j.1469-1809.2007.00406.x. Epub 2007 Dec 18.


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.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Chromosome Mapping / methods*
  • Computer Simulation
  • Genetic Predisposition to Disease / genetics*
  • Genetic Testing / methods*
  • Genomics / methods*
  • Genotype
  • Humans
  • Pedigree
  • Polymorphism, Single Nucleotide / genetics*