Lower-than-expected linkage disequilibrium between tightly linked markers in humans suggests a role for gene conversion

Understanding the pattern of linkage disequilibrium (LD) in the human genom e is important both for successful implementation of disease-gene mapping a pproaches and for inferences about human demographic histories. Previous st udies have examined LD between loci within single genes or confined genomic regions, which may not be representative of the genome; between loci separ ated by large distances, where little LD is seen; or in population groups t hat differ from one study to the next. We measured LD in a large set of loc us pairs distributed throughout the genome, with loci within each pair sepa rated by short distances (average 124 bp). Given current models of the hist ory of the human population, nearly all pairs of loci at such short distanc es would be expected to show complete LD as a consequence of lack of recomb ination in the short interval. Contrary to this expectation, a significant fraction of pairs showed incomplete LD. A standard model of recombination a pplied to these data leads to an estimate of effective human population siz e of 110,000. This estimate is an order of magnitude higher than most estim ates based on nucleotide diversity. The most likely explanation of this dis crepancy is that gene conversion increases the apparent rate of recombinati on between nearby loci.