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Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes

Proceedings of the National Academy of Sciences - PNAS, 2007-01, Vol.104 (2), p.570-575 [Peer Reviewed Journal]

Copyright 2007 The National Academy of Sciences of the United States of America ;Copyright National Academy of Sciences Jan 9, 2007 ;2006 by The National Academy of Sciences of the USA 2006 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.0610124104 ;PMID: 17197413

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Title:
Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes
Author: Butty, Vincent ; Roy, Matt ; Sabeti, Pardis ; Besse, Whitney ; Benoist, Christophe ; Mathis, Diane
Subjects: Antigens, CD - genetics ; Antigens, Differentiation - genetics ; Antigens, Differentiation, T-Lymphocyte - genetics ; Asians ; Autoimmunity - genetics ; Biological Sciences ; CD28 Antigens - genetics ; Chromosomes, Human, Pair 2 - genetics ; CTLA-4 Antigen ; Diabetes ; Ethnic Groups - genetics ; Genes ; Genetic linkage ; Genetic loci ; Genetic Variation ; Genetics, Population ; Geographic regions ; Haplotypes ; Humans ; Immune system ; Inducible T-Cell Co-Stimulator Protein ; Linkage Disequilibrium ; Lymphocyte Activation ; Polymorphism, Single Nucleotide ; Population distributions ; Population genetics ; Promoter Regions, Genetic ; Signatures ; T cell receptors ; T lymphocytes ; T-Lymphocytes - immunology
Is Part Of: Proceedings of the National Academy of Sciences - PNAS, 2007-01, Vol.104 (2), p.570-575
Description: The three members of the costimulatory receptor family, CD28, CTLA-4, and ICOS, have complementary effects on T cell activation, and their balance controls the overall outcome of immune and autoimmune responses. They are encoded in a short genomic interval, and overall activity may result from interplay between allelic variants at each locus. With multiethnic DNA panels that represent a wide spectrum of human populations, we demonstrate long-range linkage disequilibrium among the three genes. A large fraction of the variation found in the locus can be explained by the presence of extended haplotypes encompassing variants at CD28, CTLA4, and the ICOS promoter. There are unusual differences in the distribution of some variants and haplotypes between geographic regions. The differences may reflect demographic events and/or the adaptation to diverse environmental and microbial challenges encountered in the course of human migrations and will be important to consider when interpreting association to immune/autoimmune responsiveness.
Publisher: United States: National Academy of Sciences
Language: English
Identifier: ISSN: 0027-8424
EISSN: 1091-6490
DOI: 10.1073/pnas.0610124104
PMID: 17197413
Source: GFMER Free Medical Journals
MEDLINE
PubMed Central

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Signatures of strong population differentiation shape extended haplotypes across the human CD28, CTLA4, and ICOS costimulatory genes

Copyright 2007 The National Academy of Sciences of the United States of America ;Copyright National Academy of Sciences Jan 9, 2007 ;2006 by The National Academy of Sciences of the USA 2006 ;ISSN: 0027-8424 ;EISSN: 1091-6490 ;DOI: 10.1073/pnas.0610124104 ;PMID: 17197413

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