Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

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Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

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Title: Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues
Author: Kukurba, Kimberly R.; Zhang, Rui; Li, Xin; Smith, Kevin S.; Knowles, David A.; How Tan, Meng; Piskol, Robert; Lek, Monkol; Snyder, Michael; MacArthur, Daniel G.; Li, Jin Billy; Montgomery, Stephen B.

Note: Order does not necessarily reflect citation order of authors.

Citation: Kukurba, K. R., R. Zhang, X. Li, K. S. Smith, D. A. Knowles, M. How Tan, R. Piskol, et al. 2014. “Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues.” PLoS Genetics 10 (5): e1004304. doi:10.1371/journal.pgen.1004304. http://dx.doi.org/10.1371/journal.pgen.1004304.
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Abstract: Personal exome and genome sequencing provides access to loss-of-function and rare deleterious alleles whose interpretation is expected to provide insight into individual disease burden. However, for each allele, accurate interpretation of its effect will depend on both its penetrance and the trait's expressivity. In this regard, an important factor that can modify the effect of a pathogenic coding allele is its level of expression; a factor which itself characteristically changes across tissues. To better inform the degree to which pathogenic alleles can be modified by expression level across multiple tissues, we have conducted exome, RNA and deep, targeted allele-specific expression (ASE) sequencing in ten tissues obtained from a single individual. By combining such data, we report the impact of rare and common loss-of-function variants on allelic expression exposing stronger allelic bias for rare stop-gain variants and informing the extent to which rare deleterious coding alleles are consistently expressed across tissues. This study demonstrates the potential importance of transcriptome data to the interpretation of pathogenic protein-coding variants.
Published Version: doi:10.1371/journal.pgen.1004304
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006732/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:12407031
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