Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants
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Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. / Li, Yingrui; Vinckenbosch, Nicolas; Tian, Geng; Huerta-Sanchez, Emilia; Jiang, Tao; Jiang, Hui; Albrechtsen, Anders; Andersen, Gitte; Cao, Hongzhi; Korneliussen, Thorfinn Sand; Grarup, Niels; Guo, Yiran; Hellman, Ines; Jin, Xin; Li, Qibin; Liu, Jiangtao; Liu, Xiao; Sparsø, Thomas; Tang, Meifang; Wu, Honglong; Wu, Renhua; Yu, Chang; Zheng, Hancheng; Astrup, Arne; Bolund, Lars; Holmkvist, Johan; Jørgensen, Torben; Kristiansen, Karsten; Schmitz, Ole; Schwartz, Thue W; Zhang, Xiuqing; Li, Ruiqiang; Yang, Huanming; Wang, Jian; Hansen, Torben; Pedersen, Oluf; Nielsen, Rasmus; Wang, Jun.
In: Nature Genetics, Vol. 42, No. 11, 2010, p. 969-72.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants
AU - Li, Yingrui
AU - Vinckenbosch, Nicolas
AU - Tian, Geng
AU - Huerta-Sanchez, Emilia
AU - Jiang, Tao
AU - Jiang, Hui
AU - Albrechtsen, Anders
AU - Andersen, Gitte
AU - Cao, Hongzhi
AU - Korneliussen, Thorfinn Sand
AU - Grarup, Niels
AU - Guo, Yiran
AU - Hellman, Ines
AU - Jin, Xin
AU - Li, Qibin
AU - Liu, Jiangtao
AU - Liu, Xiao
AU - Sparsø, Thomas
AU - Tang, Meifang
AU - Wu, Honglong
AU - Wu, Renhua
AU - Yu, Chang
AU - Zheng, Hancheng
AU - Astrup, Arne
AU - Bolund, Lars
AU - Holmkvist, Johan
AU - Jørgensen, Torben
AU - Kristiansen, Karsten
AU - Schmitz, Ole
AU - Schwartz, Thue W
AU - Zhang, Xiuqing
AU - Li, Ruiqiang
AU - Yang, Huanming
AU - Wang, Jian
AU - Hansen, Torben
AU - Pedersen, Oluf
AU - Nielsen, Rasmus
AU - Wang, Jun
PY - 2010
Y1 - 2010
N2 - 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.
AB - 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.
KW - Base Sequence
KW - Chromosomes, Human, X
KW - Exons
KW - Gene Conversion
KW - Gene Frequency
KW - Genes, Recessive
KW - Genetic Variation
KW - Genetics, Population
KW - Human Genome Project
KW - Humans
KW - Introns
KW - Polymorphism, Single Nucleotide
KW - Untranslated Regions
U2 - 10.1038/ng.680
DO - 10.1038/ng.680
M3 - Journal article
C2 - 20890277
VL - 42
SP - 969
EP - 972
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 11
ER -
ID: 33498076