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

被引:62
作者
O'Brien, SJ [1 ]
Nelson, GW
Winkler, CA
Smith, MW
机构
[1] NCI, Lab Genom Divers, Frederick, MD 21702 USA
[2] NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA
关键词
AIDS; SNP; restriction gene; complex traits;
D O I
10.1146/annurev.genet.34.1.563
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
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.
引用
收藏
页码:563 / 591
页数:31
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