The distribution of HLA haplotypes in families with one untyped parent.

Abstract

For non-Mendelian diseases, the distribution of shared haplotypes in multiplex sibships provides a powerful tool to investigate the hypothesis that disease susceptibility genes map in the neighborhood of the HLA complex. Occasionally, ambiguous sibships arise because all offspring inherit an HLA haplotype that is identical in state from an untyped parent. The scoring procedure developed here uses the population frequency of the haplotype as well as the sibship size to estimate the probability that, with respect to the untyped parent, all sibs are identical by descent. The resulting score from an ambiguous sibship can then be combined with scores from unambiguous sibships to form the statistic suggested by Green & Woodrow. It is shown that failure to include this type of ambiguous sibship may result in a significant loss of information.