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Please use this identifier to cite or link to this item: http://repository.li.mahidol.ac.th/dspace/handle/123456789/27242
Title: Meiotic recombination generates rich diversity in NK cell receptor genes, alleles, and haplotypes
Authors: Paul J. Norman
Laurent Abi-Rached
Ketevan Gendzekhadze
John A. Hammond
Achim K. Moesta
Deepti Sharma
Thorsten Graef
Karina L. McQueen
Lisbeth A. Guethlein
Christine V.F. Carrington
Dasdayanee Chandanayingyong
Yih Hsin Chang
Catalina Crespí
Güher Saruhan-Direskeneli
Kamran Hameed
Giorgi Kamkamidze
Kwadwo A. Koram
Zulay Layrisse
Nuria Matamoros
Joan Milà
Hee Park Myoung
Ramasamy M. Pitchappan
D. Dan Ramdath
Ming Yuh Shiau
Henry A.F. Stephens
Siske Struik
Dolly Tyan
David H. Verity
Robert W. Vaughan
Ronald W. Davis
Patricia A. Fraser
Eleanor M. Riley
Mostafa Ronaghi
Peter Parham
Stanford University School of Medicine
University of The West Indies Trinidad and Tobago
Mahidol University
Chung Shan Medical University
Hospital Universitario Son Espases
Istanbul Tip Fakultesi
The Aga Khan University Hospital
Rea Rehabilitation Centre
University of Ghana
Instituto Venezolano de Investigaciones Cientificas
Seoul National University College of Medicine
Madurai Kamaraj University
Hung Kuang University Taiwan
UCL Medical School
London School of Hygiene & Tropical Medicine
Moorfields Eye Hospital NHS Foundation Trust
King's College London
Immune Disease Institute, Inc. Boston
Keywords: Biochemistry, Genetics and Molecular Biology;Medicine
Issue Date: 1-May-2009
Citation: Genome Research. Vol.19, No.5 (2009), 757-769
Abstract: Natural killer (NK) cells contribute to the essential functions of innate immunity and reproduction. Various genes encode NK cell receptors that recognize the major histocompatibility complex (MHC) Class I molecules expressed by other cells. For primate NK cells, the killer-cell immunoglobulin-like receptors (KIR) are a variable and rapidly evolving family of MHC Class I receptors. Studied here is KIR3DL1/S1, which encodes receptors for highly polymorphic human HLA-A and -B and comprises three ancient allelic lineages that have been preserved by balancing selection throughout human evolution. While the 3DS1 lineage of activating receptors has been conserved, the two 3DL1 lineages of inhibitory receptors were diversified through inter-lineage recombination with each other and with 3DS1. Prominent targets for recombination were D0-domain polymorphisms, which modulate enhancer function, and dimorphism at position 283 in the D2 domain, which influences inhibitory function. In African populations, unequal crossing over between the 3DL1 and 3DL2 genes produced a deleted KIR haplotype in which the telomeric "half" was reduced to a single fusion gene with functional properties distinct from its 3DL1 and 3DL2 parents. Conversely, in Eurasian populations, duplication of the KIR3DL1/S1 locus by unequal crossing over has enabled individuals to carry and express alleles of all three KIR3DL1/S1 lineages. These results demonstrate how meiotic recombination combines with an ancient, preserved diversity to create new KIR phenotypes upon which natural selection acts. A consequence of such recombination is to blur the distinction between alleles and loci in the rapidly evolving human KIR gene family. © 2009 by Cold Spring Harbor Laboratory Pres.
URI: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=66049110205&origin=inward
http://repository.li.mahidol.ac.th/dspace/handle/123456789/27242
ISSN: 15495469
10889051
Appears in Collections:Scopus 2006-2010

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