On the allelic spectrum of human disease

Trends Genet. 2001 Sep;17(9):502-10. doi: 10.1016/s0168-9525(01)02410-6.


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.

Publication types

  • Comparative Study

MeSH terms

  • Alleles*
  • Chromosome Mapping
  • Gene Frequency
  • Genes, Recessive
  • Genetic Linkage
  • Genetic Predisposition to Disease*
  • Genetic Variation
  • Humans
  • Models, Genetic
  • Mutation
  • Predictive Value of Tests
  • Selection, Genetic
  • X Chromosome