Consanguinity, genetic drift, and genetic diseases in populations with reduced numbers of founders

Abstract

In western countries, consanguineous marriage often arouses curiosity and prejudice in approximately equally measure, despite the fact that until the mid-nineteenth century cousin marriages were quite common in Europe and North America. Attitudes to consanguinity remain very different in other parts of the world, in particular north and sub-Saharan Africa, the Middle East, Turkey and central Asia, and south Asia, where between 20% and over 50% of current marriages are contracted between biological relatives, with first-cousin unions especially common. Besides intra-familial marriage, in these regions a large majority of marriages also occur within long-established male lineages, e.g., clans and tribes in Arab societies and castes in India. Through time these lineages effectively become separate breeding pools, with founder effect, mutation, genetic drift and bottle-necking separately and collectively influencing gene pool composition. The present chapter first considers the concepts of random and assortative mating and then examines demographic, social, economic, and religious variables that influence the prevalence of preferred types of consanguineous marriage. The effects of consanguinity on human mate choice, reproductive success, and reproductive compensation are identified, and the impact of consanguinity on morbidity and mortality in infancy, childhood and adulthood are discussed and quantified. Three detailed case studies are then used to illustrate the influence of endogamy and consanguinity on human genetic variation and genetic disease: the Finnish Disease Heritage; inter- and intra-population genetic differentiation in India; and the distribution of specific disease alleles in Arab Israeli communities. The scale of global migration during the last two generations, with many millions of individuals, families, and occasionally entire communities moving within and between continents, has created an entirely new scenario in human population genetics. Against this background, consanguinity has re-emerged both as an important feature of community and public health genetics, and as a topic of general interest.