Aberrant Gene Expression in Humans

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The uniqueness of individuals is due to differences in the combination of genetic, epigenetic and environmental determinants. Understanding the genetic basis of phenotypic variation is a key objective in genetics. Gene expression has been considered as an intermediate phenotype, and the association between gene expression and commonly-occurring genetic variants in the general population has been convincingly established. However, there are few methods to assess the impact of rare genetic variants, such as private SNPs, on gene expression. Here we describe a systematic approach, based on the theory of multivariate outlier detection, to identify individuals that show unusual or aberrant gene expression, relative the rest of the study cohort. Through characterizing detected outliers and corresponding gene sets, we are able to identify which gene sets tend to be aberrantly expressed and which individuals show deviant gene expression within a population. One of our major findings is that private SNPs may contribute to aberrant expression in outlier individuals. These private SNPs are more frequently located in the enhancer and promoter regions of genes that are aberrantly expressed, suggesting a possible regulatory function of these SNPs. Overall, our results provide new insight into the determinants of inter-individual variation, which have not been evaluated by large population-level cohort studies.

Vyšlo v časopise: Aberrant Gene Expression in Humans. PLoS Genet 11(1): e32767. doi:10.1371/journal.pgen.1004942
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004942

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