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. 1999 Jun;64(6):1728–1738. doi: 10.1086/302398

Linkage-disequilibrium mapping of disease genes by reconstruction of ancestral haplotypes in founder populations.

S K Service 1, D W Lang 1, N B Freimer 1, L A Sandkuijl 1
PMCID: PMC1377917  PMID: 10330361

Abstract

Linkage disequilibrium (LD) mapping may be a powerful means for genome screening to identify susceptibility loci for common diseases. A new statistical approach for detection of LD around a disease gene is presented here. This method compares the distribution of haplotypes in affected individuals versus that expected for individuals descended from a common ancestor who carried a mutation of the disease gene. Simulations demonstrate that this method, which we term "ancestral haplotype reconstruction" (AHR), should be powerful for genome screening of phenotypes characterized by a high degree of etiologic heterogeneity, even with currently available marker maps. AHR is best suited to application in isolated populations where affected individuals are relatively recently descended (< approximately 25 generations) from a common disease mutation-bearing founder.

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Selected References

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