This page contains links to a set of programs that use the coalescent process to generate random samples of gametes from populations at which molecular variation has accumulated according to a neutral mutation drift model of molecular evolution with recombination. Gametes generated in this manner are useful for examining patterns of linkage disequilibrium among diallelic polymorphisms in equilibrium populations. Although such populations may not actually exist, equilibrium models may better represent patterns of extant variation and disequilibrium in old populations than models which assume exponential growth or do not consider the process of new mutations entering the population (as well as mutations becoming fixed or lost in the population). Equilibrium may be especially applicable to populations which have existed at relatively large population sizes for long periods of times (e.g., Caucasians, non-island Asians, Africans). Three types of tools are available here:

		Simulate gametes
		Simulate gametes with migration
		Test power of an association study

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Simulate Gametes

This program will generate samples of gametes using a coalescent process with recombination. The user must specify the number of replicate samples, the number of gametes, the number of polymorphic sites, and the size of the region being considered in units of 4Nc.

Hudson, R.R. 1983. Properties of a neutral allele model with intragenic recombination. Theoretical Population Biology 23:183-201. PubMed

Hudson, R.R. 1987. Estimating the recombination parameter of a finite population model without selection. Genetical Research 50: 245-250. PubMed

Hudson, R.R. 1990. Gene genealogies and the coalescent process. IN Oxford Surveys in Evolutionary Biology, Vol. 7. D. Futuyma and J. Antonovics (Eds). Oxford University Press, New York.

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Simulate Gametes with Migration

This program will generate samples of gametes using a coalescant process with recombination and migration. The user must specify the number of replicate samples, the the number of polymorphic sites, and the size of the region being considered in units of 4Nc. The user also specifies a the number of gametes desired from each of N populations which are exchanging migrants according to an "island model". The number of migrants exchanged each generation between each of the populations is also specified.

Hudson, R.R. 1983. Properties of a neutral allele model with intragenic recombination. Theoretical Population Biology 23:183-201. PubMed

Hudson, R.R. 1987. Estimating the recombination parameter of a finite population model without selection. Genetical Research 50: 245-250. PubMed

Hudson, R.R. 1990. Gene genealogies and the coalescent process. IN Oxford Surveys in Evolutionary Biology, Vol. 7. D. Futuyma and J. Antonovics (Eds). Oxford University Press, New York.

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Test Power of an Association Study

This program will generate samples of diploid individuals using the same neutral coalescant process as Simulate Gametes, with the exception that one randomly chosen site (the Quantitative Trait Nucleotide, QTN) is allowed to make a user defined contribution to total phenotypic variation in a quantitative character. For each sample of diploid individuals the polymorphic site with the largest contribution to variation in the same quantitative trait is identified (the Most Significiant Marker, MSM), and the significance of this association assessed using a non-parametric permutation testing procedure. The permutation testing procedure results in a P-value being generated for each replicate simulation which represents the probability of observing an association of that magnitude between the MSM and quantitative trait by chance alone. An examination of this statistic from independent realizations of the coalescant process (in which the parameters affecting the process are held constant) allows an evaluation of different experimental designs to detect marker / phenotype associations.

Long, A.D., and C.H. Langley. 1999. The power of association studies to detect the contribution of candidate genetic loci to variation in complex traits. Genome Research 9: 720-731. PubMed | PDF (356 KB)