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Power of the affected-sib-pair method to defect disease susceptibility loci of small effect: an application to multiple sclerosis.

The distribution of marker locus identity-by-descent scores in affected sib pairs provides a powerful tool for detecting the presence of a linked non-Mendelian disease susceptibility locus. This basic approach is here extended to include a trio of sibs. A special type of sib trio consisting of two affected and one unaffected sib is investigated. It is shown that compared to affected-sib-pairs, trios with the above configuration are less efficient in detecting the presence of a linked disease susceptibility locus. When the generalized two-allele single locus model is fitted to sib pairs affected with multiple sclerosis, an estimate of the recombination fraction of 0.21 between the putative disease susceptibility locus and the HLA complex is obtained. However, this transmission model is deemed inadequate since a recombination fraction this large is inconsistent with the variety of HLA associations observed at the population level.