Health and population effects of rare gene knockouts in adult humans with related parents-Reference-Cited by-同舟云学术

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

Published:2016-04-22 Issue:6284 Volume:352 Page:474-477
ISSN:0036-8075
Container-title:Science
language:en
Short-container-title:Science

Author:

Narasimhan Vagheesh M.¹,Hunt Karen A.²,Mason Dan³,Baker Christopher L.⁴,Karczewski Konrad J.⁵⁶,Barnes Michael R.⁷,Barnett Anthony H.⁸,Bates Chris⁹,Bellary Srikanth¹⁰,Bockett Nicholas A.²,Giorda Kristina¹¹,Griffiths Christopher J.²,Hemingway Harry¹²¹³,Jia Zhilong⁷,Kelly M. Ann¹⁴,Khawaja Hajrah A.⁷,Lek Monkol⁵⁶,McCarthy Shane¹,McEachan Rosie³,O’Donnell-Luria Anne⁵⁶,Paigen Kenneth⁴,Parisinos Constantinos A.²,Sheridan Eamonn³,Southgate Laura²,Tee Louise¹⁴,Thomas Mark¹,Xue Yali¹,Schnall-Levin Michael¹¹,Petkov Petko M.⁴,Tyler-Smith Chris¹,Maher Eamonn R.¹⁵¹⁶,Trembath Richard C.²¹⁷,MacArthur Daniel G.⁵⁶,Wright John³,Durbin Richard¹,van Heel David A.²

Affiliation:

1. Wellcome Trust Sanger Institute, Hinxton, Cambridge CB10 1SA, UK.

2. Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.

3. Bradford Institute for Health Research, Bradford Teaching Hospitals National Health Service (NHS) Foundation Trust, Bradford BD9 6RJ, UK.

4. Center for Genome Dynamics, The Jackson Laboratory, Bar Harbor, ME 04609, USA.

5. Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.

6. Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.

7. William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London E1 2AT, UK.

8. Diabetes and Endocrine Centre, Heart of England NHS Foundation Trust and University of Birmingham, Birmingham B9 5SS, UK.

9. TPP, Mill House, Troy Road, Leeds LS18 5TN, UK.

10. Aston Research Centre for Healthy Ageing, Aston University, Birmingham B4 7ET, UK.

11. 10X Genomics, 7068 Koll Center Parkway, Suite 415, Pleasanton, CA 94566, USA.

12. Farr Institute of Health Informatics Research, London NW1 2DA, UK.

13. Institute of Health Informatics, University College London, London NW1 2DA, UK.

14. School of Clinical and Experimental Medicine, University of Birmingham, Birmingham B15 2TT, UK.

15. Department of Medical Genetics, University of Cambridge and National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, Box 238, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.

16. Cambridge University Hospitals NHS Foundation Trust, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.

17. Faculty of Life Sciences and Medicine, King’s College London, London SE1 1UL, UK.

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

Funder

Barts Charity

Wellcome Trust Ph.D. Studentship

NIH National Institute of General Medical Sciences

NIHR Cambridge Biomedical Research Centre

Farr Institute of Health Informatics Research, London

UK Medical Research Council

Arthritis Research UK

British Heart Foundation

Cancer Research UK

Chief Scientist Office

Economic and Social Research Council

Engineering and Physical Sciences Research Council

NIHR

National Institute for Social Care and Health Research

Wellcome Trust

NIH

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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5. Prdm9 Controls Activation of Mammalian Recombination Hotspots

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