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Am J Hum Genet. 1999 Jun;64(6):1728-38.

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

Author information

1
Neurogenetics Laboratory and Center for Neurobiology and Psychiatry, Department of Psychiatry, University of California, San Francisco, CA 94143, USA. service@ngl.ucsf.edu

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.

PMID:
10330361
PMCID:
PMC1377917
DOI:
10.1086/302398
[Indexed for MEDLINE]
Free PMC Article

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