Allelic association is increased by correlation of effective family size.
In a previous study, we showed that the observation of high frequencies of certain inherited disorders in the population of Saguenay Lac Saint Jean (SLSJ) in Quebec can be explained in terms of the variance and the auto-correlation of effective family size (EFS) across generations. Correlated EFS, across generations, allows alleles introduced as a single copy to reach very high frequencies in about 12 generations. Here, we investigate the impact of this same demographic process on allelic association between a disease locus and closely linked neutral markers. We model the fate of a disease allele, introduced as a single copy, and of its surrounding haplotype. We show that the auto-correlation of EFS across generations increases the expected proportion of individuals who carry the ancestral haplotype in the present generation. Thus, the length of a shared haplotype is longer, making this population useful for coarse mapping. But this autocorrelation decreases the estimated value; thus ignoring the auto-correlation in EFS leads to an underestimate of the recombination rate. This result is of importance, since socio-demographic processes such as auto-correlation of EFS across generations have been described in other human populations.
Austerlitz
F
F
Laboratoire Evolution et Systématique, CNRS Université Paris-Sud, Orsay, France.
Heyer
E
E
D000483:Alleles; D003198:Computer Simulation; D005191:Family Characteristics; D018703:Founder Effect; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D011995:Recombination, Genetic