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Polymorphic mobile element insertions contribute to gene expression and alternative splicing in human tissues.

Xiaolong Cao1, Yeting Zhang1,2, Lindsay M Payer3

  • 1Department of Genetics, Rutgers, The State University of New Jersey, Piscataway, NJ, 08854, USA.

Genome Biology
|July 29, 2020
PubMed
Summary

Polymorphic mobile element insertions (pMEIs) significantly impact gene expression and splicing across human tissues. This study reveals pMEIs as key regulators of tissue-specific gene activity and transcript variation.

Keywords:
Alternative splicingGene expression regulationPolymorphic mobile element insertionsQuantitative trait lociTransposable elements

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Area of Science:

  • Genomics
  • Molecular Biology
  • Human Genetics

Background:

  • Mobile elements are a major source of structural variation in the human genome.
  • Some mobile elements influence gene expression and transcript splicing.
  • The impact of polymorphic mobile element insertions (pMEIs) on tissue-specific gene regulation remains understudied.

Purpose of the Study:

  • To systematically evaluate the role of pMEIs in regulating gene expression and splicing in diverse human tissues.
  • To leverage the Genotype-Tissue Expression (GTEx) project's multi-tissue gene expression and whole genome sequencing data.

Main Methods:

  • Identification of 20,545 high-quality pMEIs from 639 individuals using GTEx whole genome sequencing data.
  • Association analysis of pMEI genotypes with gene expression (eQTLs) and splicing (sQTLs) profiles across 48 tissues.
  • Joint analysis of pMEIs and other genomic variants to predict causal roles; reporter assays for functional validation.

Main Results:

  • Discovery of thousands of pMEI-associated eQTLs and sQTLs, with pMEIs predicted as causal variants for numerous regulatory loci.
  • Demonstration of high tissue specificity for pMEI-associated regulatory effects.
  • Enrichment of pMEIs near affected genes and regulatory elements, with reporter assays confirming their functional impact on gene expression and splicing.

Conclusions:

  • pMEIs are significantly associated with widespread gene expression and splicing variations.
  • pMEIs play a crucial role in regulating tissue-specific gene expression and transcript splicing.
  • Further research into the detailed mechanisms of pMEI-mediated gene regulation in different tissues is warranted.