Population and family based studies of consanguinity : genetic and computational approaches

• Main Author: Erzurumluoglu, Abdullah Mesut
• Published: University of Bristol 2015
• Subjects: 616
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.691165

Consanguinity is the union of closely related individuals - which can have genetic implications on the health of offspring(s). Consanguineous families with disorders have been extensively analysed by geneticists and this has led to the identification of many autosomal recessive disorder causal variants and genes. Two copies of the 'inactivating' or loss of function (LoF) allele are required to cause an autosomal recessive disorder, one inherited from the mother and the other from the father. In outbreeding populations these LoF alleles very rarely meet their counterpart (as it requires both parents to possess the allele), thus are passed down the generations silently - sometimes for millennia. However, consanguineous and/ or endogamous offspring have elevated levels of homozygosity, which dramatically increases the probability of any allele to be in a homozygous (or more correctly autozygous) state. This increase in probability applies to LoF mutations also; and this elevation of levels of homozygosity is the main reason why extremely rare autosomal recessive disorders are usually only seen in populations where consanguinity (and/ or endogamy) levels are high.