Sequence features in regions of weak and strong linkage disequilibrium

被引:68
作者
Smith, AV
Thomas, DJ [1 ]
Munro, HM
Abecasis, GR
机构
[1] Univ Calif Santa Cruz, Ctr Biomol Sci & Engn, Santa Cruz, CA 95064 USA
[2] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[3] Univ Michigan, Sch Publ Hlth, Ctr Stat Genet, Ann Arbor, MI 48109 USA
关键词
D O I
10.1101/gr.4421405
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We use genotype data generated by the International HapMap Project to dissect the relationship between sequence features and the degree of linkage disequilibrium in the genome. We show that variation in linkage disequilibrium is broadly similar across Populations and examine sequence landscape in regions of strong and weak disequilibrium. Linkage disequilibrium is generally low within similar to 15 Mb of the telomeres of each chromosome and noticeably elevated in large, duplicated regions of the genome as well as within similar to 5 Mb of centromeres and other heterochromatic regions. At a broad scale (100-1000 kb resolution), Our results show that regions of strong linkage disequilibrium are typically GC poor and have reduced polymorphism. In addition, these regions are enriched for LINE repeats, but have fewer SINE, DNA, and simple repeats than the rest of the genome. At a fine scale, we examine the sequence composition of "hotspots" for the rapid breakdown of linkage disequilibrium and show that they are enriched in SINEs, in simple repeats, and in sequences that are conserved between species. Regions of high and low linkage disequilibrium (the top and bottom quartiles of the genome) have a higher density of genes and coding bases than the rest of the genome. Closer examination of the data shows that whereas some types of genes (including genes involved in immune response and sensory perception) are typically located in regions of low linkage disequilibrium, other genes (including those involved in DNA and RNA metabolism, response to DNA damage, and the cell cycle) are preferentially located in regions of strong linkage disequilibrium. Our results provide a detailed analysis of the relationship between sequence features and linkage disequilibrium and Suggest an evolutionary justification for the heterogeneity in linkage disequilibrium in the genome.
引用
收藏
页码:1519 / 1534
页数:16
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