This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wong, G. K.-S. Articles by Yu, J. Search for Related Content PubMed PubMed Citation Articles by Wong, G. K.-S. Articles by Yu, J. Social Bookmarking                   What's this?

Letter

A Population Threshold for Functional Polymorphisms

¹ University of Washington Genome Center, Department of Medicine, Seattle, Washington 98195, USA ² James Watson Institute of Zhejiang University, Hangzhou Genomics Institute, Key Laboratory of Bioinformatics of Zhejiang Province, Hangzhou 310007, China ³ Beijing Institute of Genomics, Center of Genomics and Bioinformatics, Chinese Academy of Sciences, Beijing 101300, China ⁴ Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3050, Australia ⁵ The Institute of Human Genetics, University of Aarhus, DK-8000 Århus C, Denmark

We sequenced 114 genes (for DNA repair, cell cycle arrest, apoptosis, and detoxification)in a mixed human population and observed a sudden increase in the number of functional polymorphisms below a minor allele frequency of 6%. Functionality is assessed by considering the ratio in the number of nonsynonymous single nucletide polymorphisms (SNPs)to the number of synonymous or intron SNPs. This ratio is steady from below 1% in frequency—that regime traditionally associated with rare Mendelian diseases—all the way up to about 6% in frequency, after which it falls precipitously. We consider possible explanations for this threshold effect. There are four candidates as follows: (1)deleterious variants that have yet to be purified from the population, (2)balancing selection, in which a selective advantage accrues to the heterozygotes, (3)population-specific functional polymorphisms, and (4)adaptive variants that are accumulating in the population as a response to the dramatic environmental changes of the last 7,00017,000 years.

⁶ Corresponding authors. E-MAIL gksw{at}u.washington.edu; FAX (206)685-7344. E-MAIL junyu{at}u.washington.edu; FAX (206)685-7344.

CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A. L. Hughes, B. Packer, R. Welch, A. W. Bergen, S. J. Chanock, and M. Yeager Effects of Natural Selection on Interpopulation Divergence at Polymorphic Sites in Human Protein-Coding Loci Genetics, July 1, 2005; 170(3): 1181 - 1187. [Abstract] [Full Text] [PDF]

				B. M.G. Smits, B. F.M. van Zutphen, R. H.A. Plasterk, and E. Cuppen Genetic Variation in Coding Regions Between and Within Commonly Used Inbred Rat Strains Genome Res., July 1, 2004; 14(7): 1285 - 1290. [Abstract] [Full Text] [PDF]

				A. L. Hughes, B. Packer, R. Welch, A. W. Bergen, S. J. Chanock, and M. Yeager Widespread purifying selection at polymorphic sites in human protein-coding loci PNAS, December 23, 2003; 100(26): 15754 - 15757. [Abstract] [Full Text] [PDF]