On the allelic spectrum of human disease

被引:799
作者
Reich, DE [1 ]
Lander, ES [1 ]
机构
[1] Whitehead Inst, MIT Ctr Genome Res, Cambridge, MA 02142 USA
关键词
D O I
10.1016/S0168-9525(01)02410-6
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Human disease genes show enormous variation in their allelic spectra; that is, in the number and population frequency of the disease-predisposing alleles at the loci. For some genes, there are a few predominant disease alleles. For others, there is a wide range of disease alleles, each relatively rare. The allelic spectrum is important: disease genes with only a few deleterious alleles can be more readily identified and are more amenable to clinical testing. Here, we weave together strands from the human mutation and population genetics literature to provide a framework for understanding and predicting the allelic spectra of disease genes. The theory does a reasonable job for diseases where the genetic etiology is well understood. It also has bearing on the Common Disease/Common Variants (CD/CV) hypothesis, predicting that at loci where the total frequency of disease alleles is not too small, disease loci will have relatively simple spectra.
引用
收藏
页码:502 / 510
页数:9
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