Chapter 5 - Recessive diseases and founder genetics

Abstract

Rare recessive diseases are difficult to study for one obvious reason: they are rare. It can be challenging to identify a sufficient number of cases to properly characterize a disease phenotype and subsequently identify the causative gene. Nevertheless, the quest to identify genes associated with human phenotypes, especially rare genetic diseases, has been a primary goal of genetic researchers for decades. The identification of rare disease-associated genes in humans has been greatly facilitated by the study of unusual clusters of disease, such as multiple affected members of the same family or multiple families with affected children within a special population. This chapter will define autosomal recessive inheritance, examine its role in rare pediatric disease, and review the historical contributions of founder populations and consanguineous families in unraveling the association between a rare disease and its causative gene.