bgi-LuCamp_200_exomes
An excess of rare deleterious mutations revealed by deep resequencing of 200 human exomes
we sequenced the nearly complete set of coding exons in 200 Danes, with an average fold-coverage >12x for each individual exome.
Targeted sequence capture coupled with massively parallel sequencing is a promising approach to identify genetic variants implicated in human diseases (1). Using these technologies, we sequenced the nearly complete set of coding exons in 200 Danes, with an average fold-coverage >12x for each individual exome. In the targeted regions we detected 121,895 single-nucleotide polymorphisms (SNPs), including 53,707 novel SNPs. Using a statistical method for unbiased estimation of allele frequencies we found a strong excess of rare deleterious amino acid changing mutations in our sample. This excess is more pronounced for X-linked SNPs, suggesting that deleterious substitutions are mostly recessive. Our analyses support the hypothesis that common polygenic diseases are caused by many low-frequency variants rather than a few common variants.