Study of Regions of Extended Homozygosity Provides a Powerful Method to Explore Haplotype Structure of Human Populations

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Abstract
Summary: Previous investigations have reported linkage disequilibrium occurring between nearby polymorphisms, a block‐like structure for such relationships, some instances where surprisingly few haplotypes are found and regions of extended homozygosity which are especially marked around centromeres and which are especially common on the X chromosome. We investigated the distribution and nature of regions of extended homozygosity in a sample of 1411 subjects included in a genome wide association study. Regions of extended homozygosity over 1Mb are common, with an average of 35.9 occurring per subject, and containing on average 73 homozygous markers. They have a markedly non‐random distribution. They are relatively common on the X chromosome and are seen at centromeres but are also concentrated at other chromosomal regions where presumably recombination is rare. They seem to be a consequence of some haplotypes being very common in the population and although sometimes this reflects the effect of a very common haplotype we also note that there are examples of two or three common haplotypes, each very different from each other, underlying this effect. Regions of extended homozygosity are commoner than previously appreciated. They result from the presence of extended haplotypes with high population frequency. Such regions concentrate in particular locations. The haplotypes involved are sometimes markedly disparate from each other. These regions offer a valuable opportunity for further investigation, in particular with regard to their ancestral history.