DOI: 10.1101/462390Nov 5, 2018Paper

Nonsynonymous A-to-I RNA editing contributes to burden of deleterious missense variants in healthy individuals

BioRxiv : the Preprint Server for Biology
T.-L. Mai, Trees-Juen Chuang

Abstract

ABSTARCTAdenosine-to-inosine (A-to-I) RNA editing is a very common post-transcriptional modification that can lead to A-to-G changes at the RNA level and compensate for G-to-A genomic changes to a certain extent. It has been shown that each healthy individual can carry dozens of missense variants predicted to be severely deleterious. Why strongly detrimental variants are preserved in a population and not eliminated by negative natural selection remains mostly unclear. Here we ask if RNA editing correlates with the burden of deleterious A/G polymorphisms in a population. Integrating genome and transcriptome sequencing data from 447 human lymphoblastoid cell lines, we show that nonsynonymous editing activities (prevalence/level) are negatively correlated with the deleteriousness of A-to-G genomic changes and positively correlated with that of G-to-A genomic changes within the population. We find a significantly negative correlation between nonsynonymous editing activities and allele frequency of A within the population. This negative editing-allele frequency correlation is particularly strong when editing sites are located in highly important genes/loci. Examinations of deleterious missense variants from the 1000 genomes project ...Continue Reading

Software Mentioned

Ensembl genome browser
CADD
PleiotropyDB
R
STAR aligner
liftOver
mpileup
maskOutFa
PhyloP
Ensembl

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