Health and population effects of rare gene knockouts in adult humans with related parents

Vagheesh M. Narasimhan; Karen A. Hunt; Dan Mason; Christopher L. Baker; Konrad J. Karczewski; Michael R. Barnes; Anthony Barnett; Chris Bates; Srikanth Bellary; Nicholas Bockett; Kristina Giorda; Chris Griffiths; Harry Hemingway; Zhilong Jia; M. A. Kelly; Hajrah Khawaja; Monkol Lek; Shane McCarthy; Rosemary McEachan; Anne O’Donnell‐Luria; Kenneth Paigen; Constantinos A. Parisinos; Eamonn Sheridan; Laura Southgate; Louise Tee; Mark Thomas; Yali Xue; Michael Schnall-Levin; Petko M. Petkov; Chris Tyler‐Smith; Eamonn R. Maher; Richard C. Trembath; Daniel G. MacArthur; John Wright; Richard Durbin; David A. van Heel

doi:10.1126/science.aac8624

Abstract

Rare gene knockouts in adult humans On average, most people's genomes contain approximately 100 completely nonfunctional genes. These loss-of-function (LOF) mutations tend to be rare and/or occur only as a single copy within individuals. Narasimhan et al. investigated LOF in a Pakistani population with high levels of consanguinity. Examining LOF alleles that were identical by descent, they found, as expected, an absence of homozygote LOF for certain protein-coding genes. However, they also identified many homozygote LOF alleles with no apparent deleterious phenotype, including some that were expected to confer genetic disease. Indeed, one family had lost the recombination-associated gene PRDM9 . Science , this issue p. 474

Keywords

GeneticsAlleleGene knockoutBiologyGenePhenotypeLoss functionConsanguinityPopulationHeterozygote advantageMedicine

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Publication Info

Year: 2016
Type: article
Volume: 352
Issue: 6284
Pages: 474-477
Citations: 302
Access: Closed

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APA Style

                            
                                
                                    Vagheesh M. Narasimhan, 
                                
                                    Karen A. Hunt, 
                                
                                    Dan Mason
                                
                                et al.
                            
                            (2016). 
                            Health and population effects of rare gene knockouts in adult humans with related parents. 
                            Science
                            , 352
                            (6284)
                            , 474-477.
                            https://doi.org/10.1126/science.aac8624
                        

Identifiers

DOI: 10.1126/science.aac8624