Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants.
Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs). Using a statistical method for SNP calling and an estimation of allelic frequencies based on our population data, we derived the allele frequency spectrum of cSNPs with a minor allele frequency greater than 0.02. We identified a 1.8-fold excess of deleterious, non-syonomyous cSNPs over synonymous cSNPs in the low-frequency range (minor allele frequencies between 2% and 5%). This excess was more pronounced for X-linked SNPs, suggesting that deleterious substitutions are primarily recessive.
Li
Yingrui
Y
BGI-Shenzhen, Shenzhen, China.
Vinckenbosch
Nicolas
N
Tian
Geng
G
Huerta-Sanchez
Emilia
E
Jiang
Tao
T
Jiang
Hui
H
Albrechtsen
Anders
A
Andersen
Gitte
G
Cao
Hongzhi
H
Korneliussen
Thorfinn
T
Grarup
Niels
N
Guo
Yiran
Y
Hellman
Ines
I
Jin
Xin
X
Li
Qibin
Q
Liu
Jiangtao
J
Liu
Xiao
X
Sparsø
Thomas
T
Tang
Meifang
M
Wu
Honglong
H
Wu
Renhua
R
Yu
Chang
C
Zheng
Hancheng
H
Astrup
Arne
A
Bolund
Lars
L
Holmkvist
Johan
J
Jørgensen
Torben
T
Kristiansen
Karsten
K
Schmitz
Ole
O
Schwartz
Thue W
TW
Zhang
Xiuqing
X
Li
Ruiqiang
R
Yang
Huanming
H
Wang
Jian
J
Hansen
Torben
T
Pedersen
Oluf
O
Nielsen
Rasmus
R
Wang
Jun
J
D001483:Base Sequence; D041321:Chromosomes, Human, X / Q000235:genetics; D005091:Exons / Q000235:genetics; D005785:Gene Conversion / Q000235:genetics; D005787:Gene Frequency / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D014644:Genetic Variation; D005828:Genetics, Population; D016045:Human Genome Project; D006801:Humans; D007438:Introns / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D020506:Untranslated Regions / Q000235:genetics
D020506:Untranslated Regions