Homozygosity Mapping: A Way to Map Human Recessive Traits with the DNA of Inbred Children

TLDR

The method detects disease loci by exploiting the preferential homozygosity by descent in the chromosomal region adjacent to the locus in inbred children. The authors demonstrate that a single affected child from a consanguineous marriage, analyzed with RFLPs, provides as much linkage information as a nuclear family with three affected children, enabling practical mapping of recessive disease genes using fewer than a dozen unrelated affected inbred children and opening the possibility to map many diseases lacking large multigenerational families.

Abstract

An efficient strategy for mapping human genes that cause recessive traits has been devised that uses mapped restriction fragment length polymorphisms (RFLPs) and the DNA of affected children from consanguineous marriages. The method involves detection of the disease locus by virtue of the fact that the adjacent region will preferentially be homozygous by descent in such inbred children. A single affected child of a first-cousin marriage is shown to contain the same total information about linkage as a nuclear family with three affected children. Calculations show that it should be practical to map a recessive disease gene by studying DNA from fewer than a dozen unrelated, affected inbred children, given a complete RFLP linkage map. The method should make it possible to map many recessive diseases for which it is impractical or impossible to collect adequate numbers of families with multiple affected offspring.