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Human genomics. Effect of predicted protein-truncating genetic variants on the human transcriptome

Rivas, Manuel A
Pirinen, Matti
Conrad, Donald F
Lek, Monkol
MacArthur, Daniel G.
CollaborationWith : Antonarakis, Stylianos
Published in Science. 2015, vol. 348, no. 6235, p. 666-669
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.
Keywords Alternative SplicingGene Expression ProfilingGene Expression RegulationGene SilencingGenetic VariationGenome, Human/geneticsHeterozygoteHumansNonsense Mediated mRNA DecayPhenotypeProteins/geneticsTranscriptome
PMID: 25954003
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Research groups Pathologie Moléculaire de la Trisomie 21 et le Génome Humain (248)
Population Genomics and Genetics of Complex Traits (892)
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RIVAS, Manuel A et al. Human genomics. Effect of predicted protein-truncating genetic variants on the human transcriptome. In: Science, 2015, vol. 348, n° 6235, p. 666-669. doi: 10.1126/science.1261877 https://archive-ouverte.unige.ch/unige:77383

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Deposited on : 2015-11-18

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