Dating Mutations

Abstract

The age of a mutation can be estimated from the decay of linkage disequilibrium with flanking or intragenic polymorphisms because of recombination and mutation and from the frequency of the mutation itself as a consequence of genetic drift. Several methods have been proposed, and the results from their applications can be combined with population data to provide a critical view of the origin and natural history of the mutation.

Keywords: allele age; allele frequency; linkage disequilibrium; population genetics; history

Figure 1.

Representation of two idealized shapes assumed for allele genealogy. (a) Bifurcating tree genealogy of a sample of chromosomes, a number of which descended from a chromosome carrying the nonrecurrent allele (M) that arose by mutation (denoted by the closed circle) from the common allele (N) at gt generations in the past. The most recent common ancestor of the M‐bearing chromosomes (MRCA, denoted by the open circle) dates back to gMRCA generations ago. (b) Star genealogy. The shape assumes that all M‐carrying lineages of chromosomes arose approximately at the same time (gMRCA) in the past.

Figure 2.

Graph of allele age (in generations, g) as a function of the genetic distance (recombination fraction, θ) between the mutation locus and a flanking polymorphism, according to equation []. The curves shown are for linkage disequilibrium index (δ) values of 0.6, 0.8 and 0.9.

Figure 3.

Graph of the additive correction factor (in generations, g0) of the moment estimator of allele age for an expanding population, according to the Luria–Delbrück model. The curves are obtained from eqn [] by assuming a recombination fraction, θ, between the mutation locus and the flanking polymorphism of 0.001, 0.003 and 0.01.

Figure 4.

Graph of the age (in generations, g) of a selectively neutral allele as a function of its frequency (p) in a population of constant effective size Ne=5000, according to eqn [].

Figure 5.

Graph of the approximate distribution of allele ages (in generations, g) in a population of constant effective size Ne = 5000. The curves are obtained from the derivative of eqn [] by assuming a sample of n = 1000 chromosomes and an allele frequency (p) of 0.01, 0.05 and 0.1. (Modified from Slatkin and Rannala .)

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Further Reading

Genin E, Tullio‐Pelet A, Begeot F, Lyonnet S and Abel L (2004) Estimating the age of rare disease mutations: the exaemple of triple‐A syndrome. Journal of Medical Genetics 41: 445–449.

Toomajian C, Ajioka RS, Jorde LB, Kushner JP and Kreitman M (2003) A method for detecting recent selection in the human genome from allele age estimates. Genetics 165: 287–297.

Zivelin A, Mor‐Cohen R, Kovalsky V et al. (2006) Prothrombin 20210G>A is an ancestral prothrombotic mutation that occurred in whites approximately 24 000 years ago. Blood 107: 4666–4668.

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How to Cite close
Colombo, Roberto(Dec 2007) Dating Mutations. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005462.pub2]