@article{Wong01082003,
author = {Wong, Gane Ka-Shu and Yang, Zhiyong and Passey, Douglas A. and Kibukawa, Miho and Paddock, Marcia and Liu, Chun-Rong and Bolund, Lars and Yu, Jun}, 
title = {A Population Threshold for Functional Polymorphisms},
volume = {13}, 
number = {8}, 
pages = {1873-1879}, 
year = {2003}, 
doi = {10.1101/gr.1324303}, 
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  ∼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.}, 
URL = {http://genome.cshlp.org/content/13/8/1873.abstract}, 
eprint = {http://genome.cshlp.org/content/13/8/1873.full.pdf+html}, 
journal = {Genome Research} 
}