Homozygosity mapping of recessive disease genes.

An individual with an autosomal recessive disease (filled symbol) whose parents are consanguineous will very likely be homozygous (identical) by descent for the disease allele (“mutated allele”), because a rare mutation may segregate from a common ancestor to the child through both the father's and mother's line, rendering the child homozygous for the mutation. Chromosomal segments surrounding the disease gene locus are shown here with 3 marker positions to either side. Different marker alleles are represented by different colors. Although for each parent-offspring succession there is an opportunity for a crossing over (dotted line) to occur in the parents' gametes, there is a high likelihood that in the affected child consecutive markers surrounding the mutation will not have recombined and will be identical (homozygous) by descent. This segment of homozygous markers (dotted box) can be detected as a “cZLR” peak in multipoint evaluation (see Figure S1 and Figure S2), leading to successful mapping of the disease gene. Note also that more remote consanguinity will give more opportunities for crossing over to occur and will thereby lead in the affected individual to fewer and shorter homozygous intervals that contain the disease gene (see Figures S2 and S3).