The linkage disequilibrium maps of three human chromosomes across four populations reflect their demographic history and a common underlying recombination pattern
Francisco M. De La Vega,Hadar Isaac,Andrew Collins,Charles R. Scafe,Bjarni V. Halldorsson,Bjarni V. Halldorsson,Xiaoping Su,Ross A. Lippert,Ross A. Lippert,Yu Wang,Marion Laig-Webster,Ryan T. Koehler,Janet S. Ziegle,Lewis T. Wogan,Junko Stevens,Kyle M. Leinen,Sheri J. Olson,Karl J. Guegler,Xiaoqing You,Lily Xu,Heinz G. Hemken,Francis Kalush,Mitsuo Itakura,Yi Zheng,Stephen J. O'Brien,Andrew G. Clark,Sorin Istrail,Michael W. Hunkapiller,Eugene G. Spier,Dennis A. Gilbert +29 more
TLDR
A comparison of the patterns of LD across four major human populations with a high-resolution single-nucleotide polymorphism (SNP) map covering almost the entire length of chromosomes 6, 21, and 22 and the long-range contour is remarkably similar across the four populations.Abstract:
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.read more
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Recombinational landscape and population genomics of Caenorhabditis elegans.
TL;DR: Despite the low population, effective recombination rate and extensive linkage disequilibrium among chromosomes, which are techniques that account for background levels of genomic similarity, permit association mapping in wild C. elegans strains.
Journal ArticleDOI
Extended tracts of homozygosity in outbred human populations
TL;DR: The results suggest that multiple-megabase-scale ancestral haplotypes persist in outbred human populations in broad genomic regions which have lower than average recombination rates.
Journal ArticleDOI
A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis.
Matthew R. Lincoln,Alexandre Montpetit,Alexandre Montpetit,M. Zameel Cader,M. Zameel Cader,Janna Saarela,David A. Dyment,David A. Dyment,Milvi Tiislar,Vincent Ferretti,Pentti J. Tienari,A. Dessa Sadovnick,Leena Peltonen,Leena Peltonen,George C. Ebers,George C. Ebers,Thomas J. Hudson,Thomas J. Hudson +17 more
TL;DR: It is indicated that MHC-associated susceptibility to multiple sclerosis is determined by HLA class II alleles, their interactions and closely neighboring variants.
Journal ArticleDOI
Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies
Joseph DeYoung,Maria Karayiorgou,J. Louw Roos,Herman Pretorious,Gabriel Bedoya,Jorge Ospina,Andres Ruiz-Linares,Andres Ruiz-Linares,António Macedo,Joana Almeida Palha,Peter Heutink,Yurii S. Aulchenko,Ben A. Oostra,Cornelia M. van Duijn,Marjo-Riitta Järvelin,Marjo-Riitta Järvelin,Teppo Varilo,Lynette Peddle,Proton Rahman,Giovanna Piras,Maria Monne,Sarah S. Murray,Luana Galver,Leena Peltonen,Chiara Sabatti,Andrew Collins,Nelson B. Freimer,Nelson B. Freimer +27 more
TL;DR: LD is assayed in large samples from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22 to determine the strategy for selecting markers for association studies.
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TL;DR: Comparative genomic analysis indicates vertebrate expansions of genes associated with neuronal function, with tissue-specific developmental regulation, and with the hemostasis and immune systems are indicated.
Journal ArticleDOI
dbSNP: the NCBI database of genetic variation
Stephen T. Sherry,Minghong Ward,Michael Kholodov,Jonathan Baker,Lon Phan,Elizabeth M. Smigielski,Karl Sirotkin +6 more
TL;DR: The dbSNP database is a general catalog of genome variation to address the large-scale sampling designs required by association studies, gene mapping and evolutionary biology, and is integrated with other sources of information at NCBI such as GenBank, PubMed, LocusLink and the Human Genome Project data.
Journal ArticleDOI
The International HapMap Project
John W. Belmont,Paul Hardenbol,Thomas D. Willis,Fuli Yu,Huanming Yang,Lan Yang Ch'Ang,Wei Huang,Bin Liu,Yan Shen,Paul K.H. Tam,Lap-Chee Tsui,Mary M.Y. Waye,Jeffrey Tze Fei Wong,Changqing Zeng,Qingrun Zhang,Mark S. Chee,Luana Galver,Semyon Kruglyak,Sarah S. Murray,Arnold Oliphant,Alexandre Montpetit,Fanny Chagnon,Vincent Ferretti,Martin Leboeuf,Michael S. Phillips,Andrei Verner,Shenghui Duan,Denise L. Lind,Raymond D. Miller,John P. Rice,Nancy L. Saccone,Patricia Taillon-Miller,Ming Xiao,Akihiro Sekine,Koki Sorimachi,Yoichi Tanaka,Tatsuhiko Tsunoda,Eiji Yoshino,David R. Bentley,Sarah E. Hunt,Don Powell,Houcan Zhang,Ichiro Matsuda,Yoshimitsu Fukushima,Darryl Macer,Eiko Suda,Charles N. Rotimi,Clement Adebamowo,Toyin Aniagwu,Patricia A. Marshall,Olayemi Matthew,Chibuzor Nkwodimmah,Charmaine D.M. Royal,Mark Leppert,Missy Dixon,Fiona Cunningham,Ardavan Kanani,Gudmundur A. Thorisson,Peter E. Chen,David J. Cutler,Carl S. Kashuk,Peter Donnelly,Jonathan Marchini,Gilean McVean,Simon Myers,Lon R. Cardon,Andrew P. Morris,Bruce S. Weir,James C. Mullikin,Michael Feolo,Mark J. Daly,Renzong Qiu,Alastair Kent,Georgia M. Dunston,Kazuto Kato,Norio Niikawa,Jessica Watkin,Richard A. Gibbs,Erica Sodergren,George M. Weinstock,Richard K. Wilson,Lucinda Fulton,Jane Rogers,Bruce W. Birren,Hua Han,Hongguang Wang,Martin Godbout,John C. Wallenburg,Paul L'Archevêque,Guy Bellemare,Kazuo Todani,Takashi Fujita,Satoshi Tanaka,Arthur L. Holden,Francis S. Collins,Lisa D. Brooks,Jean E. McEwen,Mark S. Guyer,Elke Jordan,Jane Peterson,Jack Spiegel,Lawrence M. Sung,Lynn F. Zacharia,Karen Kennedy,Michael Dunn,Richard Seabrook,Mark Shillito,Barbara Skene,John Stewart,David Valle,Ellen Wright Clayton,Lynn B. Jorde,Aravinda Chakravarti,Mildred K. Cho,Troy Duster,Troy Duster,Morris W. Foster,Maria Jasperse,Bartha Maria Knoppers,Pui-Yan Kwok,Julio Licinio,Jeffrey C. Long,Pilar N. Ossorio,Vivian Ota Wang,Charles N. Rotimi,Patricia Spallone,Patricia Spallone,Sharon F. Terry,Eric S. Lander,Eric H. Lai,Deborah A. Nickerson,Gonçalo R. Abecasis,David Altshuler,Michael Boehnke,Panos Deloukas,Julie A. Douglas,Stacey Gabriel,Richard R. Hudson,Thomas J. Hudson,Leonid Kruglyak,Yusuke Nakamura,Robert L. Nussbaum,Stephen F. Schaffner,Stephen T. Sherry,Lincoln Stein,Toshihiro Tanaka +145 more
TL;DR: The HapMap will allow the discovery of sequence variants that affect common disease, will facilitate development of diagnostic tools, and will enhance the ability to choose targets for therapeutic intervention.
Journal ArticleDOI
The Structure of Haplotype Blocks in the Human Genome
Stacey Gabriel,Stephen F. Schaffner,Huy Nguyen,Jamie Moore,Jessica Roy,Brendan Blumenstiel,John M. Higgins,Matthew DeFelice,Amy L. Lochner,Maura Faggart,Shau Neen Liu-Cordero,Charles N. Rotimi,Adebowale Adeyemo,Richard S. Cooper,Ryk Ward,Eric S. Lander,Mark J. Daly,David Altshuler,David Altshuler +18 more
TL;DR: It is shown that the human genome can be parsed objectively into haplotype blocks: sizable regions over which there is little evidence for historical recombination and within which only a few common haplotypes are observed.
Journal ArticleDOI
Sequence the Human Genome
TL;DR: This book aims to provide a history of Chinese modern art from 17th Century to the present day through the lens of 20th Century critics, practitioners, journalists, and mediaeval and modern-day critics.
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