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Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants
Nat Genet, 42 (11): 969--972 (ноября 2010)
Аннотация
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.
From angsd manual: frequency based on base counts. This method does not rely on genotype likelihood or probabilities but instead infers the allele frequency directly on the base counts.
