期刊
AMERICAN JOURNAL OF HUMAN GENETICS
卷 108, 期 8, 页码 1401-1408出版社
CELL PRESS
DOI: 10.1016/j.ajhg.2021.06.008
关键词
-
资金
- NIH [R01AG066490, R01MH125244, U01HG009431, R01HL142015, R01HG008150, U01HG009080, DK107437, HL142015, DK112348, R01HG010140]
- Stanford School of Medicine Department of Pathology [1T32AG047126-01]
- NLM training grant [LM007033]
- National Science Foundation Graduate Research Fellowship [DGE 1656518]
- Stanford Center for Computational, Evolutionary and Human Genomics
- NIH Center for Multi-and Trans-ethnic Mapping of Mendelian and Complex Diseases grant [5U01 HG009080]
- National Institutes of Health S10 Instrumentation Grant [S10OD023452]
- NHGRI of the NIH [R01HG010140]
Through RNA sequencing, it was found that the efficiency of NMD induced by PTVs can be evaluated using allelic imbalance. A predictive model was established, revealing that variant position, allele frequency, and other factors can predict allelic imbalance, and the NMD effects are highly consistent across different tissues and individuals.
Precise interpretation of the effects of rare protein-truncating variants (PTVs) is important for accurate determination of variant impact. Current methods for assessing the ability of PTVs to induce nonsense-mediated decay (NMD) focus primarily on the position of the variant in the transcript. We used RNA sequencing of the Genotype Tissue Expression v.8 cohort to compute the efficiency of NMD using allelic imbalance for 2,320 rare (genome aggregation database minor allele frequency <= 1%) PTVs across 809 individuals in 49 tissues. We created an interpretable predictive model using penalized logistic regression in order to evaluate the comprehensive influence of variant annotation, tissue, and inter-individual variation on NMD. We found that variant position, allele frequency, the inclusion of ultra-rare and singleton variants, and conservation were predictive of allelic imbalance. Furthermore, we found that NMD effects were highly concordant across tissues and individuals. Due to this high consistency, we demonstrate in silico that utilizing peripheral tissues or cell lines provides accurate prediction of NMD for PTVs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据