Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions

Ann Hum Genet. 2016 May;80(3):187-96. doi: 10.1111/ahg.12150. Epub 2016 Mar 22.


Consanguineous offspring have elevated levels of homozygosity. Autozygous stretches within their genome are likely to harbour loss of function (LoF) mutations which will lead to complete inactivation or dysfunction of genes. Studying consanguineous offspring with clinical phenotypes has been very useful for identifying disease causal mutations. However, at present, most of the genes in the human genome have no disorder associated with them or have unknown function. This is presumably mostly due to the fact that homozygous LoF variants are not observed in outbred populations which are the main focus of large sequencing projects. However, another reason may be that many genes in the genome-even when completely "knocked out," do not cause a distinct or defined phenotype. Here, we discuss the benefits and implications of studying consanguineous populations, as opposed to the traditional approach of analysing a subset of consanguineous families or individuals with disease. We suggest that studying consanguineous populations "as a whole" can speed up the characterisation of novel gene functions as well as indicating nonessential genes and/or regions in the human genome. We also suggest designing a single nucleotide variant (SNV) array to make the process more efficient.

Keywords: Consanguineous populations; Mendelian disease; autozygosity; complex disease; gene function.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Chromosome Mapping
  • Consanguinity*
  • Gene Silencing
  • Genetics, Population*
  • Genome, Human*
  • Heterozygote
  • Homozygote
  • Humans
  • Phenotype