Allelic Disequilibrium and Allele Frequency Distribution as a
Function of Social and Demographic History
E.A. Thompson and J.V. Neel
Department of Statistics, University of Washington, Seattle 98195,
USA.
thompson@stat.washington.edu
American Journal of Human Genetics ,
60(1), 197-204 (Jan 1997)
Abstract
Allelic disequilibrium between closely linked genes is a common
observation in human populations and often gives rise to speculation
concerning the role of selective forces. In a previous treatment, we have
developed a population model of the expected distribution of rare variants
(including private polymorphisms) in Amerindians and have argued that,
because of the great expansion of Amerindian numbers with the advent of
agriculture, most of these rare variants are of relatively recent origin. Many
other populations have similar histories of striking recent expansions. In this
treatment, we demonstrate that, in consequence of this fact, a high degree of
linkage disequilibrium between two nonhomologous alleles <0.5 cM apart is the
"normal" expectation, even in the absence of selection. This expectation is
enhanced by the previous subdivision of human populations into relatively
isolated tribes characterized by a high level of endogamy and inbreeding. We
also demonstrate that the alleles associated with a recessive disease phenotype
are expected to exist in a population in very variable frequencies: there is no
need to postulate positive selection with respect to the more common
disease-associated alleles for such entities as phenylketonuria or cystic fibrosis.
Association Studies