Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues

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Gene expression is a fundamental cellular process that contributes to phenotypic diversity. Gene expression can vary between alleles of an individual through differences in genomic imprinting or cis-acting regulatory variation. Distinguishing allelic activity is important for informing the abundance of altered mRNA and protein products. Advances in sequencing technologies allow us to quantify patterns of allele-specific expression (ASE) in different individuals and cell-types. Previous studies have identified patterns of ASE across human populations for single cell-types; however the degree of tissue-specificity of ASE has not been deeply characterized. In this study, we compare patterns of ASE across multiple tissues from a single individual using whole transcriptome sequencing (RNA-Seq) and a targeted, high-resolution assay (mmPCR-Seq). We detect patterns of ASE for rare deleterious and loss-of-function protein-coding variants, informing the frequency at which allelic expression could modify the functional impact of personal deleterious protein-coding across tissues. We demonstrate that these interactions occur for one third of such variants however large direction flips in allelic expression are infrequent.

Vyšlo v časopise: Allelic Expression of Deleterious Protein-Coding Variants across Human Tissues. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004304
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004304

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