Investigating the genetic basis of RNA Editing in humans

Adenosine deaminases acting on RNA (ADAR) are proteins that deaminate adenosine to inosine, which is then recognized by the ribosome as guanosine. To study the genetic basis of RNA editing efficiency by ADAR, we carried out deep RNA sequencing (RNA-Seq) in human B-cells and uncovered more than 100,000 RNA editing sites. Next, we evaluated the extent of individual variation in the RNA editing among unrelated individuals from Centre d''Etude du Polymorphisme Humain (CEPH) and found significant variation in the levels of editing. To understand whether there exists a genetic component to the variation in RNA editing levels, we obtained RNA-Seq data from 10 pairs of monozygotic twins. These results revealed that there exists a significant genetic component to variation in RNA editing. Overall design: To identify RNA editing sites, we obtained RNA-Seq data for 2 unrelated individuals. To study individual variation in RNA editing, we analyzed RNA-Seq data in sets of 12 and 41 unrelated individuals. Lastly, to understand the genetic basis of variation in RNA editing, we studied related individuals, namely 10 pairs of monozygotic twins and large families.