Population-specific recombination sites within the human MHC region |
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Authors: | T H Lam M Shen J-M Chia S H Chan E C Ren |
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Institution: | 1.Singapore Immunology Network,
A*STAR, Singapore;2.Department of Microbiology, Yong Loo Lin
School of Medicine, National University of Singapore, Singapore;3.Cold Spring Harbor Laboratory, New York, NY, USA |
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Abstract: | Genetic rearrangement by recombination is one of the major driving forces for genome
evolution, and recombination is known to occur in non-random, discreet recombination sites
within the genome. Mapping of recombination sites has proved to be difficult,
particularly, in the human MHC region that is complicated by both population variation and
highly polymorphic HLA genes. To overcome these problems, HLA-typed individuals
from three representative populations: Asian, European and African were used to generate
phased HLA haplotypes. Extended haplotype homozygosity (EHH) plots constructed from the
phased haplotype data revealed discreet EHH drops corresponding to recombination events
and these signatures were observed to be different for each population. Surprisingly, the
majority of recombination sites detected are unique to each population, rather than being
common. Unique recombination sites account for 56.8% (21/37 of total sites) in
the Asian cohort, 50.0% (15/30 sites) in Europeans and 63.2% (24/38
sites) in Africans. Validation carried out at a known sperm typing recombination site of
45 kb (HLA-F-telomeric) showed that EHH was an efficient method to narrow
the recombination region to 826 bp, and this was further refined to 660 bp
by resequencing. This approach significantly enhanced mapping of the genomic architecture
within the human MHC, and will be useful in studies to identify disease risk genes. |
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Keywords: | MHC recombination sites HLA haplotypes Asian |
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