Evolutionary constraint and disease associations of post-translational modification sites in human genomes.

ABSTRACT: Interpreting the impact of human genome variation on phenotype is challenging. The functional effect of protein-coding variants is often predicted using sequence conservation and population frequency data, however other factors are likely relevant. We hypothesized that variants in protein post-translational modification (PTM) sites contribute to phenotype variation and disease. We analyzed fraction of rare variants and non-synonymous to synonymous variant ratio (Ka/Ks) in 7,500 human genomes and found a significant negative selection signal in PTM regions independent of six factors, including conservation, codon usage, and GC-content, that is widely distributed across tissue-specific genes and function classes. PTM regions are also enriched in known disease mutations, suggesting that PTM v

SUBMITTER: Reimand J 

PROVIDER: S-EPMC4303425 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature