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

Alex Coventry, Lara M. Bull-Otterson, Xiaoming Liu, Andrew G. Clark, Taylor J. Maxwell, Jacy Crosby, James E. Hixson, Thomas J. Rea, Donna M. Muzny, Lora R. Lewis, David A. Wheeler, Aniko Sabo, Christine Lusk, Kenneth G. Weiss, Humeira Akbar, Andrew Cree, Alicia C. Hawes, Irene Newsham, Robin T. Varghese, Donna VillasanaShannon Gross, Vandita Joshi, Jireh Santibanez, Margaret Morgan, Kyle Chang, Walker Hale IV, Alan R. Templeton, Eric Boerwinkle, Richard Gibbs, Charles F. Sing

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Article number131
JournalNature Communications
Issue number8
StatePublished - 2010
Externally publishedYes

ASJC Scopus subject areas

  • General Physics and Astronomy
  • General Chemistry
  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'Deep resequencing reveals excess rare recent variants consistent with explosive population growth'. Together they form a unique fingerprint.

Cite this