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Annu Rev Genet. 2000;34:563-591.

Polygenic and multifactorial disease gene association in man: Lessons from AIDS.

Author information

  • 1Laboratory of Genomic Diversity, National Cancer Institute, Intramural Research Support Program, SAIC Frederick, National Cancer Institute-Frederick Cancer Research and Development Center, Frederick, Maryland 21702-1201, USA. obrien@ncifcrf.gov

Abstract

In an age when the majority of monogenic human disease genes have been identified, a particular challenge for the coming generation of human geneticists will be resolving complex polygenic and multifactorial diseases. The tools of molecular and population genetic association have much potential as well as peril in uncovering small cryptic genetic effects in disease. We have used a candidate gene approach to identify eight distinct human loci with alleles that in different ways influence the outcome of exposure to HIV-1, the AIDS virus. The successes in these gene hunts have validated the approach and illustrate the strengths and limitations of association analysis in an actual case history. The integration of genetic associations, well-described clinical cohorts, extensive basic research on AIDS pathogenesis, and functional interpretation of gene connections to disease offers a formula for detecting such genes in complex human genetic phenotypes.

PMID:
11092839
[PubMed - indexed for MEDLINE]
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