Deep resequencing reveals excess rare recent variants consistent with explosive population growth

被引：169

作者：

Coventry, Alex ^{[1
]}

Bull-Otterson, Lara M. ^{[2
]}

Liu, Xiaoming ^{[3
]}

Clark, Andrew G. ^{[1
]}

Maxwell, Taylor J. ^{[3
]}

Crosby, Jacy ^{[3
]}

Hixson, James E. ^{[3
]}

Rea, Thomas J. ^{[4
]}

Muzny, Donna M. ^{[2
]}

Lewis, Lora R. ^{[2
]}

Wheeler, David A. ^{[2
]}

Sabo, Aniko ^{[2
]}

Lusk, Christine ^{[4
]}

Weiss, Kenneth G. ^{[4
]}

Akbar, Humeira ^{[2
]}

Cree, Andrew ^{[2
]}

Hawes, Alicia C. ^{[2
]}

Newsham, Irene ^{[2
]}

Varghese, Robin T. ^{[2
]}

Villasana, Donna ^{[2
]}

Gross, Shannon ^{[2
]}

Joshi, Vandita ^{[2
]}

Santibanez, Jireh ^{[2
]}

Morgan, Margaret ^{[2
]}

Chang, Kyle ^{[2
]}

Hale, Walker ^{[2
]}

Templeton, Alan R. ^{[5
]}

Boerwinkle, Eric ^{[3
]}

Gibbs, Richard ^{[2
]}

Sing, Charles F. ^{[4
]}

机构：

[1] Cornell Univ, Dept Mol Biol & Genet, Ithaca, NY 14853 USA

[2] Baylor Coll Med, Dept Mol & Human Genet, Human Genome Sequencing Ctr, Houston, TX 77030 USA

[3] UT Houston Hlth Sci Ctr, Ctr Human Genet, Houston, TX 77030 USA

[4] Univ Michigan, Sch Med, Dept Human Genet, Ann Arbor, MI 48109 USA

[5] Washington Univ, Dept Biol, St Louis, MO 63130 USA

来源：

NATURE COMMUNICATIONS | 2010年 / 1卷

关键词：

SEQUENCE; GENOME; NUCLEOTIDE; SAMPLE; COMMON; SNPS;

D O I：

10.1038/ncomms1130

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Accurately determining the distribution of rare variants is an important goal of human genetics, but resequencing of a sample large enough for this purpose has been unfeasible until now. Here, we applied Sanger sequencing of genomic PCR amplicons to resequence the diabetes-associated genes KCNJ11 and HHEX in 13,715 people (10,422 European Americans and 3,293 African Americans) and validated amplicons potentially harbouring rare variants using 454 pyrosequencing. We observed far more variation (expected variant-site count similar to 578) than would have been predicted on the basis of earlier surveys, which could only capture the distribution of common variants. By comparison with earlier estimates based on common variants, our model shows a clear genetic signal of accelerating population growth, suggesting that humanity harbours a myriad of rare, deleterious variants, and that disease risk and the burden of disease in contemporary populations may be heavily influenced by the distribution of rare variants.

引用

页数：6

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