Abstract
The sampling distributions of several statistics that measure the association of alleles on gametes (linkage disequilibrium) are estimated under a two-locus neutral infinite allele model using an efficient Monte Carlo method. An often used approximation for the mean squared linkage disequilibrium is shown to be inaccurate unless the proper statistical conditioning is used. The joint distribution of linkage disequilibrium and the allele frequencies in the sample is studied. This estimated joint distribution is sufficient for obtaining an approximate maximum likelihood estimate of C = 4 Nc, where N is the population size and c is the recombination rate. It has been suggested that observations of high linkage disequilibrium might be a good basis for rejecting a neutral model in favor of a model in which natural selection maintains genetic variation. It is found that a single sample of chromosomes, examined at two loci cannot provide sufficient information for such a test if C < 10, because with C this small, very high levels of linkage disequilibrium are not unexpected under the neutral model. In samples of size 50, it is found that, even when C is as large as 50, the distribution of linkage disequilibrium conditional on the allele frequencies is substantially different from the distribution when there is no linkage between the loci. When conditioned on the number of alleles at each locus in the sample, all of the sample statistics examined are nearly independent of θ = 4Nµ, where µ is the neutral mutation rate.
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Selected References
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- Hudson R. R. Properties of a neutral allele model with intragenic recombination. Theor Popul Biol. 1983 Apr;23(2):183–201. doi: 10.1016/0040-5809(83)90013-8. [DOI] [PubMed] [Google Scholar]
- Karlin S., McGregor J. Rates and probabilities of fixation for two locus random mating finite populations without selection. Genetics. 1968 Jan;58(1):141–159. doi: 10.1093/genetics/58.1.141. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ohta T., Kimura M. Linkage disequilibrium between two segregating nucleotide sites under the steady flux of mutations in a finite population. Genetics. 1971 Aug;68(4):571–580. doi: 10.1093/genetics/68.4.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Strobeck C., Morgan K. The effect of intragenic recombination on the number of alleles in a finite population. Genetics. 1978 Apr;88(4):829–844. doi: 10.1093/genetics/88.4.829. [DOI] [PMC free article] [PubMed] [Google Scholar]