Document Type

Article

Publication Date

10-18-2019

Publication Title

Science

Volume

366

Issue

6463

Pages

351-356

Publisher Name

American Association for the Advancement of Science

Abstract

Transcriptome data can facilitate the interpretation of the effects of rare genetic variants. Here, we introduce ANEVA (analysis of expression variation) to quantify genetic variation in gene dosage from allelic expression (AE) data in a population. Application of ANEVA to the Genotype-Tissues Expression (GTEx) data showed that this variance estimate is robust and correlated with selective constraint in a gene. Using these variance estimates in a dosage outlier test (ANEVA-DOT) applied to AE data from 70 Mendelian muscular disease patients showed accuracy in detecting genes with pathogenic variants in previously resolved cases and led to one confirmed and several potential new diagnoses. Using our reference estimates from GTEx data, ANEVA-DOT can be incorporated in rare disease diagnostic pipelines to use RNA-sequencing data more effectively.

Comments

Author Posting © The Authors, 2019. This is the author's version of the work. It is posted here by permission of The Authors for personal use, not for redistribution. The definitive version was published in Science, Volume 366, Issue 6463, July 2019. https://doi.org/10.1126/science.aay0256

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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