期刊
NATURE GENETICS
卷 48, 期 4, 页码 359-+出版社
NATURE PORTFOLIO
DOI: 10.1038/ng.3510
关键词
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资金
- National Human Genome Research Institute [R01HG006855]
- Yerkes Center [P51OD011132]
- US National Institutes of Health/National Heart, Lung, and Blood Institute K99 award [1K99HL122515-01A1]
- Juvenile Diabetes Research Foundation [JDRF 3-APF-2014-111-A-N]
- National Heart, Lung, and Blood Institute of the US National Institutes of Health [K01HL125751]
One of the first protein polymorphisms identified in humans involves the abundant blood protein haptoglobin. Two exons of the HP gene (encoding haptoglobin) exhibit copy number variation that affects HP protein structure and multimerization. The evolutionary origins and medical relevance of this polymorphism have been uncertain. Here we show that this variation has likely arisen from many recurring deletions, more specifically, reversions of an ancient hominin-specific duplication of these exons. Although this polymorphism has been largely invisible to genome-wide genetic studies thus far, we describe a way to analyze it by imputation from SNP haplotypes and find among 22,288 individuals that these HP exonic deletions associate with reduced LDL and total cholesterol levels. We further show that these deletions, and a SNP that affects HP expression, appear to drive the strong association of cholesterol levels with SNPs near HP. Recurring exonic deletions in HP likely enhance human health by lowering cholesterol levels in the blood.
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