Allele Spectrum of Human Genetic Disease


The allelic spectrum of a disease refers to the number of places in the genome in which DNA sequence variation affects a specified disease, and the relative frequencies of these individual alleles in a population or sample. Most variants will be relatively rare compared with other alleles at their respective location and most typically will have individually weak effects on the risk of the disease. Because variation arises locally by mutation, and spreads only slowly, and because most variants are due to recent mutation, the predominant part of the spectrum consists of many rare variants. However, for all but the simplest of diseases, the effect of a variant, and hence its presence in the disease's allelic spectrum, is dependent on the individual genomic and environmental contexts in which it is found.

Key Concepts

  • Mutation and recombination produce variation.
  • The amount of variation varies over time and among populations.
  • Allelic variation contributing to disease is often spread across many sites within a gene or many genes.
  • The frequency of most variants is small, as are their typical effects.
  • The effects of an allele typically depend on its genomic and environmental context in the individual.

Keywords: genetic architecture; allele frequencies; allele spectrum; genotype–phenotype relationships; genetic variation

Figure 1. Relative frequencies of 444 alleles associated with PKU. PAHdb.


Hartl DL and Clark AG (2007) Principles of Population Genetics. Sunderland, MA: Sinauer.

Weiss K and Buchanan A (2004) Genetics and the Logic of Evolution. New York: John Wiley & Sons.

Weiss K and Buchanan A (2011) Is life law‐like? Genetics 188: 761–771.

The above are general works about the nature and origins of genetic variation. For specific topics in this fast‐changing topic the best references are found by web browsing.

Web Links

Gene Cards (the human gene database).

Genomewide association study data resource.

HMGD (human gene mutation data base).

OMIM (online Mendelian inheritance in man).

PAHdb (phenylalanine hydroxylase data base).

OMMID (The online metabolic and molecular bases of inherited disease).

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How to Cite close
Weiss, Kenneth M(May 2017) Allele Spectrum of Human Genetic Disease. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0006033.pub2]