title: Allele multiplicity in simple Mendelian disorders.
abstract: A model of selection involving two selectively equivalent classes of alleles at a locus is considered. One class consists of normal alleles A1, A2, A3,. . .; the other class consists of detrimental alleles a1, a2, a3, . . . . Mutation within and between allelic classes can occur without restriction, but selection operates in such a way as to maintain an approximately constant overall frequency of A-type and a-type alleles is derived, and it is shown that the distribution of allele frequencies in a sample of detrimental alleles depends on the forward (A to a) mutation rate but not on the selection coefficient, degree of dominance, or mutation rate among a-type alleles. Recurrent mutation therefore generates allelic multiplicity among detrimental alleles, and this is discussed in the context of clinical heterogeneity in simple Mendelian disorders.
mesh_terms: D000483:Alleles; D005787:Gene Frequency; D005826:Genetics, Medical; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D011336:Probability; D012641:Selection, Genetic