title: Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants.
abstract: 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.
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Yingrui
authors.initials: Y
authors.lastname: Li
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vinckenbosch
authors.forename: Geng
authors.initials: G
authors.lastname: Tian
authors.forename: Emilia
authors.initials: E
authors.lastname: Huerta-Sanchez
authors.forename: Tao
authors.initials: T
authors.lastname: Jiang
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Anders
authors.initials: A
authors.lastname: Albrechtsen
authors.forename: Gitte
authors.initials: G
authors.lastname: Andersen
authors.forename: Hongzhi
authors.initials: H
authors.lastname: Cao
authors.forename: Thorfinn
authors.initials: T
authors.lastname: Korneliussen
authors.forename: Niels
authors.initials: N
authors.lastname: Grarup
authors.forename: Yiran
authors.initials: Y
authors.lastname: Guo
authors.forename: Ines
authors.initials: I
authors.lastname: Hellman
authors.forename: Xin
authors.initials: X
authors.lastname: Jin
authors.forename: Qibin
authors.initials: Q
authors.lastname: Li
authors.forename: Jiangtao
authors.initials: J
authors.lastname: Liu
authors.forename: Xiao
authors.initials: X
authors.lastname: Liu
authors.forename: Thomas
authors.initials: T
authors.lastname: Sparsø
authors.forename: Meifang
authors.initials: M
authors.lastname: Tang
authors.forename: Honglong
authors.initials: H
authors.lastname: Wu
authors.forename: Renhua
authors.initials: R
authors.lastname: Wu
authors.forename: Chang
authors.initials: C
authors.lastname: Yu
authors.forename: Hancheng
authors.initials: H
authors.lastname: Zheng
authors.forename: Arne
authors.initials: A
authors.lastname: Astrup
authors.forename: Lars
authors.initials: L
authors.lastname: Bolund
authors.forename: Johan
authors.initials: J
authors.lastname: Holmkvist
authors.forename: Torben
authors.initials: T
authors.lastname: Jørgensen
authors.forename: Karsten
authors.initials: K
authors.lastname: Kristiansen
authors.forename: Ole
authors.initials: O
authors.lastname: Schmitz
authors.forename: Thue W
authors.initials: TW
authors.lastname: Schwartz
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhang
authors.forename: Ruiqiang
authors.initials: R
authors.lastname: Li
authors.forename: Huanming
authors.initials: H
authors.lastname: Yang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.forename: Rasmus
authors.initials: R
authors.lastname: Nielsen
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
mesh_terms: 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
chemical_list: D020506:Untranslated Regions