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

 
TitleDeep resequencing reveals excess rare recent variants consistent with explosive population growth.
Publication TypeJournal Article
Year of Publication2010
AuthorsCoventry, A, Bull-Otterson, LM, Liu, X, Clark, AG, Maxwell, TJ, Crosby, J, Hixson, JE, Rea, TJ, Muzny, DM, Lewis, LR, Wheeler, DA, Sabo, A, Lusk, C, Weiss, KG, Akbar, H, Cree, A, Hawes, AC, Newsham, I, Varghese, RT, Villasana, D, Gross, S, Joshi, V, Santibanez, J, Morgan, M, Chang, K, Iv, WHale, Templeton, AR, Boerwinkle, E, Gibbs, RA, Sing, CF
JournalNat Commun
Volume1
Pagination131
Date Published2010 Nov 30
ISSN2041-1723
Abstract

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 ∼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.

DOI10.1038/ncomms1130
Alternate JournalNat Commun
PubMed ID21119644
PubMed Central IDPMC3060603
Grant ListR01 HL072904 / HL / NHLBI NIH HHS / United States
R01 HL072810-06 / HL / NHLBI NIH HHS / United States
R01 HL072810-05A1 / HL / NHLBI NIH HHS / United States
R01 HL072810-03 / HL / NHLBI NIH HHS / United States
R01 HL072810-07 / HL / NHLBI NIH HHS / United States
R01 HL072810-04 / HL / NHLBI NIH HHS / United States
R01 HL072810 / HL / NHLBI NIH HHS / United States
U54 HG003273 / HG / NHGRI NIH HHS / United States
P50 GM065509 / GM / NIGMS NIH HHS / United States
R01 HL072905-09 / HL / NHLBI NIH HHS / United States
R01 HL072904-08 / HL / NHLBI NIH HHS / United States
R01 HL072905 / HL / NHLBI NIH HHS / United States
R01 HL072810-09 / HL / NHLBI NIH HHS / United States
R01 HL072810-01 / HL / NHLBI NIH HHS / United States
R01 HL072810-08 / HL / NHLBI NIH HHS / United States
R01 HL072810-02 / HL / NHLBI NIH HHS / United States