Homozygosity mapping: one more tool in the clinical geneticist's toolbox

Abstract

Consanguinity increases the coefficient of inbreeding, which increases the likelihood of presence of pathogenic mutations in a homoallelic state. Although this is known to have an adverse outcome by increasing the risk of autosomal recessive disorders, this very phenomenon has also made homozygosity mapping the most robust gene discovery strategy in the recent history of human genetics. However, homozygosity mapping can also serve as an extremely powerful tool in the clinical genetics setting as well. In particular, this method is highly suited in the setting of genetically heterogeneous conditions and inborn errors of metabolism that require sophisticated biochemical testing that may not be readily available. This article is meant to highlight the clinical utility of this strategy using illustrative clinical examples from the author's own clinical genetics practice.