Human Genomics. Effect of Predicted Protein-truncating Genetic Variants on the Human Transcriptome

Overview

Journal Science

Specialty Science

Date 2015 May 9

PMID 25954003

Citations 167

Authors

Manuel A Rivas

Matti Pirinen

Donald F Conrad

Monkol Lek

Emily K Tsang

Konrad J Karczewski

Julian B Maller

Kimberly R Kukurba

David S DeLuca

Menachem Fromer

Pedro G Ferreira

Kevin S Smith

Rui Zhang

Fengmei Zhao

Eric Banks

Ryan Poplin

Douglas M Ruderfer

Shaun M Purcell

Taru Tukiainen

Eric V Minikel

Peter D Stenson

David N Cooper

Katharine H Huang

Timothy J Sullivan

Jared Nedzel

Carlos D Bustamante

Jin Billy Li

Mark J Daly

Roderic Guigo

Peter Donnelly

Kristin Ardlie

Michael Sammeth

Emmanouil T Dermitzakis

Mark I McCarthy

Stephen B Montgomery

Tuuli Lappalainen

Daniel G MacArthur

Affiliations

Soon will be listed here.

Abstract

Accurate prediction of the functional effect of genetic variation is critical for clinical genome interpretation. We systematically characterized the transcriptome effects of protein-truncating variants, a class of variants expected to have profound effects on gene function, using data from the Genotype-Tissue Expression (GTEx) and Geuvadis projects. We quantitated tissue-specific and positional effects on nonsense-mediated transcript decay and present an improved predictive model for this decay. We directly measured the effect of variants both proximal and distal to splice junctions. Furthermore, we found that robustness to heterozygous gene inactivation is not due to dosage compensation. Our results illustrate the value of transcriptome data in the functional interpretation of genetic variants.

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