On the allelic spectrum of human disease.
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.
Reich
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The Whitehead Institute/MIT Center for Genome Research, Nine Cambidge Center, Cambridge, MA 02142, USA. reich@genome.wi.mit.edu
Lander
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D000483:Alleles; D002874:Chromosome Mapping; D005787:Gene Frequency; D005808:Genes, Recessive; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D011237:Predictive Value of Tests; D012641:Selection, Genetic; D014960:X Chromosome