Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/38726
Title: Importance of Genetic Studies in Consanguineous Populations for the Characterization of Novel Human Gene Functions.
Authors: Erzurumluoglu, A. Mesut
Shihab, H. A.
Rodriguez, S.
Gaunt, T. R.
Day, I. N.
First Published: 22-Mar-2016
Publisher: Wiley for University College London
Citation: Annals of Human Genetics, 2016, 80 (3), pp. 187-196
Abstract: 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.
DOI Link: 10.1111/ahg.12150
ISSN: 0003-4800
eISSN: 1469-1809
Links: http://onlinelibrary.wiley.com/doi/10.1111/ahg.12150/abstract
http://hdl.handle.net/2381/38726
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: © 2016 The Authors. Annals of Human Genetics published by University College London (UCL) and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Description: Additional Supporting Information may be found in the online version of this article: Table S1: Potential LoF Mutations in the Human Genome. Figure S1: Comparison between offspring of outbred individuals and first cousins using the example of an allele for which q = 0.1 (frequency of 1 in 10 in a population) and there are three unrelated homozygotes (i.e., AA) who marry into the family. Figure S2: Comparison between offspring of outbred individuals and first cousins using the example of an allele for which q = 0.001 (frequency of 1 in thousand in a population). Figure S3: Example of a complex pedigree with multiple consanguineous unions. Figure S4: Factors influenced by consanguineous unions and/or by living in a highly consanguineous region. Figure S5: Autozygosity mapping and consanguinity.
Appears in Collections:Published Articles, Dept. of Health Sciences

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