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Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors

The KIR complex appears to be evolving rapidly in humans, and more than 50 different haplotypes have been described, ranging from four to 14 KIR loci. Previously it has been suggested that most KIR haplotypes consist of framework genes, present in all individuals, which bracket a variable number of...

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Autores principales: Jiang, Wei, Johnson, Chris, Jayaraman, Jyothi, Simecek, Nikol, Noble, Janelle, Moffatt, Miriam F., Cookson, William O., Trowsdale, John, Traherne, James A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460180/
https://www.ncbi.nlm.nih.gov/pubmed/22948769
http://dx.doi.org/10.1101/gr.137976.112
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author Jiang, Wei
Johnson, Chris
Jayaraman, Jyothi
Simecek, Nikol
Noble, Janelle
Moffatt, Miriam F.
Cookson, William O.
Trowsdale, John
Traherne, James A.
author_facet Jiang, Wei
Johnson, Chris
Jayaraman, Jyothi
Simecek, Nikol
Noble, Janelle
Moffatt, Miriam F.
Cookson, William O.
Trowsdale, John
Traherne, James A.
author_sort Jiang, Wei
collection PubMed
description The KIR complex appears to be evolving rapidly in humans, and more than 50 different haplotypes have been described, ranging from four to 14 KIR loci. Previously it has been suggested that most KIR haplotypes consist of framework genes, present in all individuals, which bracket a variable number of other genes. We used a new technique to type 793 families from the United Kingdom and United States for both the presence/absence of all individual KIR genes as well as copy number and found that KIR haplotypes are even more complex. It is striking that all KIR loci are subject to copy number variation (CNV), including the so-called framework genes, but CNV is much more frequent in KIR B haplotypes than KIR A haplotypes. These two basic KIR haplotype groups, A and B, appear to be following different evolutionary trajectories. Despite the great diversity, there are 11 common haplotypes, derived by reciprocal recombination near KIR2DL4, which collectively account for 94% of KIR haplotypes determined in Caucasian samples. These haplotypes could be derived from combinations of just three centromeic and two telomeric motifs, simplifying disease analysis for these haplotypes. The remaining 6% of haplotypes displayed novel examples of expansion and contraction of numbers of loci. Conventional KIR typing misses much of this additional complexity, with important implications for studying the genetics of disease association with KIR that can now be explored by CNV analysis.
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spelling pubmed-34601802012-10-06 Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors Jiang, Wei Johnson, Chris Jayaraman, Jyothi Simecek, Nikol Noble, Janelle Moffatt, Miriam F. Cookson, William O. Trowsdale, John Traherne, James A. Genome Res Research The KIR complex appears to be evolving rapidly in humans, and more than 50 different haplotypes have been described, ranging from four to 14 KIR loci. Previously it has been suggested that most KIR haplotypes consist of framework genes, present in all individuals, which bracket a variable number of other genes. We used a new technique to type 793 families from the United Kingdom and United States for both the presence/absence of all individual KIR genes as well as copy number and found that KIR haplotypes are even more complex. It is striking that all KIR loci are subject to copy number variation (CNV), including the so-called framework genes, but CNV is much more frequent in KIR B haplotypes than KIR A haplotypes. These two basic KIR haplotype groups, A and B, appear to be following different evolutionary trajectories. Despite the great diversity, there are 11 common haplotypes, derived by reciprocal recombination near KIR2DL4, which collectively account for 94% of KIR haplotypes determined in Caucasian samples. These haplotypes could be derived from combinations of just three centromeic and two telomeric motifs, simplifying disease analysis for these haplotypes. The remaining 6% of haplotypes displayed novel examples of expansion and contraction of numbers of loci. Conventional KIR typing misses much of this additional complexity, with important implications for studying the genetics of disease association with KIR that can now be explored by CNV analysis. Cold Spring Harbor Laboratory Press 2012-10 /pmc/articles/PMC3460180/ /pubmed/22948769 http://dx.doi.org/10.1101/gr.137976.112 Text en © 2012, Published by Cold Spring Harbor Laboratory Press This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genome.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 3.0 Unported License), as described at http://creativecommons.org/licenses/by-nc/3.0/.
spellingShingle Research
Jiang, Wei
Johnson, Chris
Jayaraman, Jyothi
Simecek, Nikol
Noble, Janelle
Moffatt, Miriam F.
Cookson, William O.
Trowsdale, John
Traherne, James A.
Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
title Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
title_full Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
title_fullStr Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
title_full_unstemmed Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
title_short Copy number variation leads to considerable diversity for B but not A haplotypes of the human KIR genes encoding NK cell receptors
title_sort copy number variation leads to considerable diversity for b but not a haplotypes of the human kir genes encoding nk cell receptors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3460180/
https://www.ncbi.nlm.nih.gov/pubmed/22948769
http://dx.doi.org/10.1101/gr.137976.112
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