Figure 1.

Schematic showing inheritance pattern for a small stretch of DNA. The grey region indicates an allelic variant associated with disorder. The region denoted by a, b, c, or d is a highly polymorphic noncoding region that can be used as a marker, because it is unlikely that two unrelated individuals will have identical DNA in this region. Combinations a–c, a–d, b–c, and b–d for this region are equally common in the offspring, so the a priori likelihood that any two children will have 0, 1, or 2 alleles IBD is 1 : 2 : 1. If affected sib pairs show a departure from this 1 : 2 : 1 IBD ratio, this suggests that the marker is close to an allelic variant of interest. The correlation between the marker, a, and the grey region will not be perfect, because stretches of DNA can become separated in meiosis due to crossing-over: The closer the marker is to the grey region, the more likely it is to be coinherited. In another set of families, we may see different DNA variants at this locus (w, x, y, and z instead of a, b, c, and d), but the same logic is applied: Thus the key issue is not the form that the marker takes, but rather whether it has the same parental origin in two affected sibs.