Sampling variance and distribution of the D ' measure of overall gametic disequilibrium between multiallelic loci

Citation
C. Zapata et al., Sampling variance and distribution of the D ' measure of overall gametic disequilibrium between multiallelic loci, ANN HUM GEN, 65, 2001, pp. 395-406
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Molecular Biology & Genetics
Journal title
ANNALS OF HUMAN GENETICS
ISSN journal
0003-4800 → ACNP
Volume
65
Year of publication
2001
Part
4
Pages
395 - 406
Database
ISI
SICI code
0003-4800(200107)65:<395:SVADOT>2.0.ZU;2-G
Abstract
The development of the theory of estimation of gametic disequilibrium for m ultiallelic systems is particularly necessary, since a large number of the genetic markers available at present are highly polymorphic multiallelic sy stems. The D' coefficient is one of the most commonly used measures of the extent of overall disequilibrium between all possible pairs of alleles at t wo multiallelic loci. Nevertheless, the sampling properties of this measure of overall disequilibrium, are to date, unknown. In this work, we have der ived explicit, expressions by large-sample theory to compute the approximat e sampling variance of (D) over cap' between pairs of multiallelic loci, wh en samples of haplotypes are taken from populations. Formulae for calculati ng the asymptotic sampling variance were by Monte Carlo simulation. In addi tion, the magnitude of the sampling variance of (D) over cap' was investiga ted under different scenarios of disequilibrium between multiallelic loci. Extensive simulations, were also carried out, for describing the sampling d istribution of (D) over cap', conditioned on the sample size, number of all eles and their frequencies, and disequilibrium components. It was found tha t the sampling distribution of (D) over cap' generally approaches well the theoretical normal distribution for experimental sample sizes, particularly when loci have many alleles. Disequilibrium data between microsatellite lo ci of human chromosome 11p are used for illustration. These investigations increase substantially our knowledge about this widely used measure of over all disequilibrium, which is relevant to evaluate disequilibrium between mu ltiallelic loci in populations.