The development of the theory of estimation of gametic disequilibrium for multiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic systems. The Dh coefficient is one of the most commonly used measures of the extent of overall disequilibrium between all possible pairs of alleles at two multiallelic loci. Nevertheless, the sampling properties of this measure of overall disequilibrium, are to date, unknown. In this work, we have derived explicit expressions by large-sample theory to compute the approximate sampling variance of D< h between pairs of multiallelic loci, when samples of haplotypes are taken from populations. Formulae for calculating the asymptotic sampling variance were checked by Monte Carlo simulation. In addition, the magnitude of the sampling variance of D< h was investigated under different scenarios of disequilibrium between multiallelic loci. Extensive simulations were also carried out for describing the sampling distribution of D< h, conditioned on the sample size, number of alleles and their frequencies, and disequilibrium components. It was found that the sampling distribution of D< h generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite loci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of overall disequilibrium, which is relevant to evaluate disequilibrium between multiallelic loci in populations. The study of non-random association of alleles at different loci, or gametic disequilibrium, is useful for revealing the location and relationships of the genes along the chromosomes, the relative influence of different evolutionary forces, and the history of populations. Searching for gametic disequilibrium between pairs of multiallelic loci often makes use of the theory of estimation for the two-allele, twolocus model.
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Localization of the gene for familial dysautonomia on chromosome 9 and definition of DNA markers for genetic diagnosis. Nat Genet 4:160-163 Bouchard G. De Braekeleer M (eds) (1990) Histoire d'un genome. Presses de l'Universite du Quebec, Quebec Davies N (1984) God's playground: a history of Poland. Columbia University Press, New York De Braekeleer M (1991) Hereditary disorders in Saguenay-Lac-St-Jean (Quebec, Canada). Hum Hered 41:141-146 Diamond JM, Rotter JI (1987) Observing the founder effect in human evolution. Nature 329:105-106 Gauvreau D, Guerien M, Hamel M (1990) De Charlevoix au Saguenay: mesure et caracteristiques du mouvement migratoire avant 1911. In: Bouchard G, De Braekeleer M (eds) Histoire d'un genome. Presses
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