Detecting recent positive selection in the human genome from haplotype structure

Nature
Pardis C SabetiEric S Lander

Abstract

The ability to detect recent natural selection in the human population would have profound implications for the study of human history and for medicine. Here, we introduce a framework for detecting the genetic imprint of recent positive selection by analysing long-range haplotypes in human populations. We first identify haplotypes at a locus of interest (core haplotypes). We then assess the age of each core haplotype by the decay of its association to alleles at various distances from the locus, as measured by extended haplotype homozygosity (EHH). Core haplotypes that have unusually high EHH and a high population frequency indicate the presence of a mutation that rose to prominence in the human gene pool faster than expected under neutral evolution. We applied this approach to investigate selection at two genes carrying common variants implicated in resistance to malaria: G6PD and CD40 ligand. At both loci, the core haplotypes carrying the proposed protective mutation stand out and show significant evidence of selection. More generally, the method could be used to scan the entire genome for evidence of recent positive selection.

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May 20, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Fuquan ZhangPozi Liu
Jun 22, 2013·Evolutionary Applications·Estelle Vasseur, Lluis Quintana-Murci
Jun 10, 2011·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Rungnapa IttiwutJoel Gelernter
Aug 11, 2010·The New Phytologist·Mathieu SiolSpencer C H Barrett
Sep 17, 2013·Evolution; International Journal of Organic Evolution·Pierre-Alexandre GagnaireLouis Bernatchez
Jun 30, 2011·Diabetic Medicine : a Journal of the British Diabetic Association·K DietrichP Kovacs
May 14, 2011·Molecular Ecology Resources·Wolfgang Stephan
Jun 22, 2011·Molecular Ecology·Mathieu Gautier, Michel Naves
Mar 28, 2013·Ecology and Evolution·Zach GompertMatthew L Forister
Nov 30, 2011·Molecular Ecology·R LaurentR Chaix
Dec 8, 2011·Genetic Epidemiology·F Anthony San LucasPaul Scheet
Jan 26, 2010·Animal Genetics·Saber QanbariH Simianer
Apr 18, 2012·Genetic Epidemiology·Wagner C S MagalhãesEduardo Tarazona-Santos
Dec 24, 2010·Annals of the New York Academy of Sciences·Lluis Quintana-Murci, Luis B Barreiro
Oct 3, 2012·Evolution; International Journal of Organic Evolution·Vera S DominguesHopi E Hoekstra
May 27, 2010·Evolution; International Journal of Organic Evolution·Jay F Storz, Christopher W Wheat
Apr 1, 2015·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·K E KemperM E Goddard
Dec 5, 2013·Evolution; International Journal of Organic Evolution·Matthew R JonesStéphanie Manel
Jan 30, 2015·Evolutionary Anthropology·George H Perry
Jan 1, 2014·American Journal of Physical Anthropology·Milena R ShattuckRipan S Malhi
Aug 19, 2007·American Journal of Human Genetics·Hua TangNeil J Risch
Aug 8, 2015·Molecular Biology and Evolution·Colin A MacleanJames G D Prendergast
Mar 15, 2006·American Journal of Human Genetics·Yali XueChris Tyler-Smith
Apr 13, 2004·American Journal of Human Genetics·E WangR K Moyzis
Apr 17, 2004·American Journal of Human Genetics·C J HoggartPaul M McKeigue
Dec 31, 2005·American Journal of Human Genetics·Neil A HanchardDominic P Kwiatkowski
Oct 7, 2004·Theoretical Population Biology·Graham Coop, Robert C Griffiths
Jun 29, 2004·Trends in Genetics : TIG·Martin Kreitman, Anna Di Rienzo
Jan 18, 2006·American Journal of Human Genetics·Etienne PatinLluis Quintana-Murci
Feb 9, 2006·American Journal of Human Genetics·Jonathan MarchiniInternational HapMap Consortium
Jun 30, 2004·Blood Cells, Molecules & Diseases·Anthi DrousiotouSarah A Tishkoff
Jun 22, 2010·American Journal of Human Genetics·Alexandra ZhernakovaCisca Wijmenga
Sep 25, 2015·Canine Genetics and Epidemiology·Elizabeth R ArnottClaire M Wade
Aug 1, 2015·Journal of Human Genetics·Paula S RamosCarl D Langefeld
May 7, 2015·Molecular Ecology·Anna Fijarczyk, Wiesław Babik
Oct 7, 2006·Seminars in Immunology·Susana CampinoAlain Dessein
Sep 30, 2006·The Lancet Infectious Diseases·David BurgnerJenefer M Blackwell
Aug 1, 2006·Trends in Microbiology·Olivier NeyrollesLluis Quintana-Murci
Jul 1, 2006·Trends in Genetics : TIG·Shameek Biswas, Joshua M Akey
Oct 26, 2005·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Henry Harpending, Gregory Cochran
May 16, 2006·Autoimmunity Reviews·Kenneth AbelAndreas Braun
May 11, 2006·American Journal of Human Genetics·Andrew E FryDominic P Kwiatkowski
Jul 15, 2004·American Journal of Human Genetics·Brian C Verrelli, Sarah A Tishkoff
Apr 24, 2015·The New Phytologist·Jason G BraggJustin O Borevitz
Apr 25, 2015·Animal Genetics·Ezequiel L NicolazziAlessandra Stella
Mar 18, 2016·Genome Biology and Evolution·Marte SodelandHalvor Knutsen
Sep 4, 2014·Animal Genetics·A L SomavillaLuciana Regitano
May 1, 2013·Asian-Australasian Journal of Animal Sciences·Dajeong LimSeung Hwan Lee
Jul 23, 2014·Journal of Animal Breeding and Genetics = Zeitschrift Für Tierzüchtung Und Züchtungsbiologie·P StratzJ Bennewitz
Dec 3, 2014·Theoretical Population Biology·Hua ChenMontgomery Slatkin
Jun 10, 2015·Human Genetics·Bryony Leigh JonesDallas M Swallow
Jul 23, 2015·BMC Genomics·Qianqian ZhangGoutam Sahana
Apr 23, 2015·Molecular Biology and Evolution·Maxime BonhommeChristophe Jacquet
Nov 16, 2005·Annual Review of Genetics·Rasmus Nielsen
Jun 18, 2015·Frontiers in Genetics·Pablo Orozco-terWengelMichael W Bruford
Mar 20, 2015·Molecular Biology and Evolution·Ming-Shan WangYa-Ping Zhang
Apr 17, 2016·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Takashi AkagiRyutaro Tao