The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern

The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-r...

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Published in:	Genome research Vol. 15; no. 4; pp. 454 - 462
Main Authors:	De La Vega, Francisco M, Isaac, Hadar, Collins, Andrew, Scafe, Charles R, Halldórsson, Bjarni V, Su, Xiaoping, Lippert, Ross A, Wang, Yu, Laig-Webster, Marion, Koehler, Ryan T, Ziegle, Janet S, Wogan, Lewis T, Stevens, Junko F, Leinen, Kyle M, Olson, Sheri J, Guegler, Karl J, You, Xiaoqing, Xu, Lily H, Hemken, Heinz G, Kalush, Francis, Itakura, Mitsuo, Zheng, Yi, de Thé, Guy, O'Brien, Stephen J, Clark, Andrew G, Istrail, Sorin, Hunkapiller, Michael W, Spier, Eugene G, Gilbert, Dennis A
Format:	Journal Article
Language:	English
Published:	United States Cold Spring Harbor Laboratory Press 01-04-2005
Subjects:	African Americans - genetics African Continental Ancestry Group - genetics Asian Continental Ancestry Group - genetics Chromosome Mapping Chromosomes, Human, Pair 21 Chromosomes, Human, Pair 22 Chromosomes, Human, Pair 6 Demography European Continental Ancestry Group - genetics Genetics, Population Humans Linkage Disequilibrium Polymorphism, Single Nucleotide Recombination, Genetic
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Summary:	The extent and patterns of linkage disequilibrium (LD) determine the feasibility of association studies to map genes that underlie complex traits. Here we present a comparison of the patterns of LD across four major human populations (African-American, Caucasian, Chinese, and Japanese) with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22. We constructed metric LD maps formulated such that the units measure the extent of useful LD for association mapping. LD reaches almost twice as far in chromosome 6 as in chromosomes 21 or 22, in agreement with their differences in recombination rates. By all measures used, out-of-Africa populations showed over a third more LD than African-Americans, highlighting the role of the population's demography in shaping the patterns of LD. Despite those differences, the long-range contour of the LD maps is remarkably similar across the four populations, presumably reflecting common localization of recombination hot spots. Our results have practical implications for the rational design and selection of SNPs for disease association studies.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 Present address: St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.3241705. Article published online before print in March 2005. Freely available online through the Genome Research Immediate Open Access option. Present address: deCode Genetics, 101 Reykjavik, Iceland Present address: Department of Mathematics, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA. Corresponding author. E-mail delavefm@appliedbiosystems.com ; fax (650) 554-2577.
ISSN:	1088-9051 1549-5469
DOI:	10.1101/gr.3241705