Major factors influencing linkage disequilibrium by analysis of different chromosome regions in distinct populations: demography chromosome recombination frequency and selection

Linkage disequilibrium (LD) mapping of disease genes is complicated by popu lation- and chromosome-region-specific factors. We have analysed demographi c factors by contrasting intermarker LD results obtained in a large cosmopo litan population (UK), a targe genetic isolate (Sardinia) and a subisolate (village of Gavoi) for two regions of the X chromosome. A dramatic increase of LD was found in the subisolate. Demographic history of populations ther efore influences LD. Chromosome-region-specific effects, namely the pattern and frequency of homologous recombination, were next delineated by the ana lysis of chromosome 6p21, including the HLA region. Patterns of global LD i n this region were very similar in the UK and Sardinian populations despite their entirely distinct demographies, and correlate well with the pattern of recombinations. Nevertheless, haplotypes extend across recombination hot spots indicative of selection of certain haplotypes, Subisolate aside, chr omosome-region-specific differences in LD patterns appear to be more import ant than the differences in intermarker LD between distinct populations.