title: A population threshold for functional polymorphisms.
abstract: 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 approximately 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 7000 approximately 17000 years.
authors.affiliation: University of Washington Genome Center, Department of Medicine, Seattle, Washington 98195, USA. gksw@u.washington.edu
authors.forename: Gane Ka-Shu
authors.initials: GK
authors.lastname: Wong
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Yang
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Passey
authors.forename: Miho
authors.initials: M
authors.lastname: Kibukawa
authors.forename: Marcia
authors.initials: M
authors.lastname: Paddock
authors.forename: Chun-Rong
authors.initials: CR
authors.lastname: Liu
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.forename: Jun
authors.initials: J
authors.lastname: Yu
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000706:statistics & numerical data; D030541:Databases, Genetic / Q000706:statistics & numerical data; D005787:Gene Frequency / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D005828:Genetics, Population / Q000379:methods / Q000706:statistics & numerical data; D006071:Gorilla gorilla; D006801:Humans; D002679:Pan troglodytes; D011110:Polymorphism, Genetic / Q000235:genetics* / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics / Q000502:physiology; D012641:Selection, Genetic