Predicting the range of linkage disequilibrium

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Abstract
A much pondered question in the Middle Ages was, “How many angels can dance on the head of a pin?” Today, we pose more sensible questions but answers are not necessarily getting easier. A generally accepted strategy in the mapping of a disease gene is to initially apply linkage analysis for an approximate estimate of the location of the trait gene and to subsequently make use of linkage disequilibrium (association) for a more accurate localization. The thinking behind this approach has been that disequilibrium extends over much shorter distances from a disease gene than does linkage. On the other hand, biotechnology companies are gearing up to develop large numbers of single nucleotide polymorphism (SNP) markers (1) to localize disease genes by the disequilibrium mapping approach alone, for example, in case-control studies. It is then of interest to know how many such markers will be required on a genome-wide basis. Thus, the question is, how rapidly does disequilibrium decay as one moves away from a disease locus? The answer to this question is obviously of more than academic interest. Whether several 1,000 or several 100,000 SNP markers are needed will have a major impact on such association mapping studies. An early prediction was that in large outbred populations, disequilibrium should …