RT Journal
A1 Wong, Gane Ka-Shu
A1 Yang, Zhiyong
A1 Passey, Douglas A.
A1 Kibukawa, Miho
A1 Paddock, Marcia
A1 Liu, Chun-Rong
A1 Bolund, Lars
A1 Yu, Jun
T1 A Population Threshold for Functional Polymorphisms
JF Genome Research 
JO Genome Research 
YR 2003 
FD August 01 
VO 13 
IS 8 
SP 1873 
OP 1879 
DO 10.1101/gr.1324303 
UL http://genome.cshlp.org/content/13/8/1873.abstract 
AB 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 7,000∼17,000 years.