Orion: Detecting regions of the human non-coding genome that are intolerant to variation using population genetics.

Published

Journal Article

There is broad agreement that genetic mutations occurring outside of the protein-coding regions play a key role in human disease. Despite this consensus, we are not yet capable of discerning which portions of non-coding sequence are important in the context of human disease. Here, we present Orion, an approach that detects regions of the non-coding genome that are depleted of variation, suggesting that the regions are intolerant of mutations and subject to purifying selection in the human lineage. We show that Orion is highly correlated with known intolerant regions as well as regions that harbor putatively pathogenic variation. This approach provides a mechanism to identify pathogenic variation in the human non-coding genome and will have immediate utility in the diagnostic interpretation of patient genomes and in large case control studies using whole-genome sequences.

Full Text

Duke Authors

Cited Authors

  • Gussow, AB; Copeland, BR; Dhindsa, RS; Wang, Q; Petrovski, S; Majoros, WH; Allen, AS; Goldstein, DB

Published Date

  • January 2017

Published In

Volume / Issue

  • 12 / 8

Start / End Page

  • e0181604 -

PubMed ID

  • 28797091

Pubmed Central ID

  • 28797091

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

International Standard Serial Number (ISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0181604

Language

  • eng