@article{cb47f8e398604e3e834c32e9b4320ca3,
title = "A High-Density Admixture Map for Disease Gene Discovery in African Americans",
abstract = "Admixture mapping (also known as {"}mapping by admixture linkage disequilibrium,{"} or MALD) provides a way of localizing genes that cause disease, in admixed ethnic groups such as African Americans, with ∼100 times fewer markers than are required for whole-genome haplotype scans. However, it has not been possible to perform powerful scans with admixture mapping because the method requires a dense map of validated markers known to have large frequency differences between Europeans and Africans. To create such a map, we screened through databases containing ∼450,000 single-nucleotide polymorphisms (SNPs) for which frequencies had been estimated in African and European population samples. We experimentally confirmed the frequencies of the most promising SNPs in a multiethnic panel of unrelated samples and identified 3,011 as a MALD map (1.2 cM average spacing). We estimate that this map is ∼70% informative in differentiating African versus European origins of chromosomal segments. This map provides a practical and powerful tool, which is freely available without restriction, for screening for disease genes in African American patient cohorts. The map is especially appropriate for those diseases that differ in incidence between the parental African and European populations.",
author = "Smith, {Michael W.} and Nick Patterson and Lautenberger, {James A.} and Truelove, {Ann L.} and McDonald, {Gavin J.} and Alicja Waliszewska and Kessing, {Bailey D.} and Malasky, {Michael J.} and Charles Scafe and Ernest Le and {De Jager}, {Philip L.} and Mignault, {Andre A.} and Zeng Yi and {De Th{\'e}}, Guy and Myron Essex and Sankal{\'e}, {Jean Louis} and Moore, {Jason H.} and Kwabena Poku and Phair, {John P.} and Goedert, {James J.} and David Vlahov and Williams, {Scott M.} and Tishkoff, {Sarah A.} and Winkler, {Cheryl A.} and {De La Vega}, {Francisco M.} and Trevor Woodage and Sninsky, {John J.} and Hafler, {David A.} and David Altshuler and Gilbert, {Dennis A.} and O'Brien, {Stephen J.} and David Reich",
note = "Funding Information: We are grateful to the many individuals whose DNA samples were used in this study and to Robert Ferrell for sharing the Beni samples from Nigeria. Technical help came from Ellen Frazier, Kui Gong, Shanise Hill, Guo Kui Pei, Carolyn Whistler, Lewis Wogan, Xiaoqing You, and Janet Ziegle. We thank Mark Adams, Michele Cargill, Jean-Paul Chretien, Josef Coresh, Michael Dean, Allen Kane, Michael Klag, and Eric Lander for contributing important insights or data. N.P. is supported by a National Institutes of Health (NIH) K-01 award (grant HG002758-01), P.L.D. is supported by National Institute of Neurological Disorders and Stroke grant K08 NS046341 and is the William C. Fowler Scholar in multiple sclerosis research, and J.H.M., K.P., and S.M.W. are supported by NIH grant HL-65234. D.R. is the recipient of a Career Development Award from the Burroughs Wellcome Fund. D.A. is a Burroughs-Wellcome Fund Clinical Scholar in Translational Research, as well as a Charles E. Culpeper Medical Scholar. The experimental work at the NCI was made possible by reagents contributed by Applied Biosystems and was funded by an NIH/NCI contract (NO1-CO-12400). The experimental work at the Broad Institute was made possible by subcontract U19-AI50864 from the NIH/National Institute of Allergy and Infectious Diseases, a grant from the Wadsworth Foundation, and a grant from the National Multiple Sclerosis Society (to D.R. and D.A.H.). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. government. ",
year = "2004",
month = may,
doi = "10.1086/420856",
language = "English (US)",
volume = "74",
pages = "1001--1013",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "5",
}