2009_PLoSGenetics_Price_HAPMIX

2009_PLoSGenetics_Price_HAPMIX - Sensitive Detection of...

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Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations Alkes L. Price 1,2,3 , Arti Tandon 3,4 , Nick Patterson 3 , Kathleen C. Barnes 5 , Nicholas Rafaels 5 , Ingo Ruczinski 6 , Terri H. Beaty 6 , Rasika Mathias 7 , David Reich 3,4 * , Simon Myers 3,8,9 * 1 Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 2 Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, United States of America, 3 Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America, 4 Department of Genetics, Harvard Medical School, Boston, Massachusetts, United States of America, 5 Johns Hopkins Allergy and Asthma Center, Division of Clinical Immunology, Department of Medicine, School of Medicine, Baltimore, Maryland, United States of America, 6 Department of Biostatistics, Johns Hopkins School of Public Health, Baltimore, Maryland, United States of America, 7 Inherited Disease Research Branch, National Human Genome Research Institute, National Institutes of Health, Baltimore, Maryland, United States of America, 8 Department of Statistics, Oxford University, Oxford, United Kingdom, 9 Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom Abstract Identifying the ancestry of chromosomal segments of distinct ancestry has a wide range of applications from disease mapping to learning about history. Most methods require the use of unlinked markers; but, using all markers from genome- wide scanning arrays, it should in principle be possible to infer the ancestry of even very small segments with exquisite accuracy. We describe a method, HAPMIX, which employs an explicit population genetic model to perform such local ancestry inference based on fine-scale variation data. We show that HAPMIX outperforms other methods, and we explore its utility for inferring ancestry, learning about ancestral populations, and inferring dates of admixture. We validate the method empirically by applying it to populations that have experienced recent and ancient admixture: 935 African Americans from the United States and 29 Mozabites from North Africa. HAPMIX will be of particular utility for mapping disease genes in recently admixed populations, as its accurate estimates of local ancestry permit admixture and case-control association signals to be combined, enabling more powerful tests of association than with either signal alone. Citation: Price AL, Tandon A, Patterson N, Barnes KC, Rafaels N, et al. (2009) Sensitive Detection of Chromosomal Segments of Distinct Ancestry in Admixed Populations. PLoS Genet 5(6): e1000519. doi:10.1371/journal.pgen.1000519 Editor: Jonathan K. Pritchard, University of Chicago, United States of America Received October 27, 2008; Accepted May 15, 2009; Published June 19, 2009 This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
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This note was uploaded on 03/20/2010 for the course BIOCHEM 410 taught by Professor Whien during the Winter '10 term at Ohio State.

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2009_PLoSGenetics_Price_HAPMIX - Sensitive Detection of...

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