@article {1387,
	title = {Evolution and functional impact of rare coding variation from deep sequencing of human exomes.},
	journal = {Science},
	volume = {337},
	year = {2012},
	month = {2012 Jul 06},
	pages = {64-9},
	abstract = {<p>As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111{\texttimes} in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86\% with a minor allele frequency less than 0.5\%), previously unknown (82\%), and population-specific (82\%). On average, 2.3\% of the 13,595 SNVs each person carried were predicted to affect protein function of ~313 genes per genome, and ~95.7\% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.</p>},
	keywords = {African Americans, Disease, European Continental Ancestry Group, Evolution, Molecular, Exome, Female, Gene Frequency, Genetic Association Studies, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, High-Throughput Nucleotide Sequencing, Humans, Male, Polymorphism, Single Nucleotide, Population Growth, Selection, Genetic},
	issn = {1095-9203},
	doi = {10.1126/science.1219240},
	author = {Tennessen, Jacob A and Bigham, Abigail W and O{\textquoteright}Connor, Timothy D and Fu, Wenqing and Kenny, Eimear E and Gravel, Simon and McGee, Sean and Do, Ron and Liu, Xiaoming and Jun, Goo and Kang, Hyun Min and Jordan, Daniel and Leal, Suzanne M and Gabriel, Stacey and Rieder, Mark J and Abecasis, Goncalo and Altshuler, David and Nickerson, Deborah A and Boerwinkle, Eric and Sunyaev, Shamil and Bustamante, Carlos D and Bamshad, Michael J and Akey, Joshua M}
}
