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Cell Lineage Analyses and Gene Function Studies Using Twin-spot MARCM
Published on: March 2, 2017
Mapping cis- and trans-regulatory effects across multiple tissues in twins
Elin Grundberg1, Kerrin S Small, Åsa K Hedman
1Wellcome Trust Sanger Institute, Hinxton, UK.
Nature Genetics
|September 4, 2012
Summary
Genetic factors significantly influence gene expression and disease risk. Our study reveals that rare variants, not just common ones, drive heritable gene expression, impacting complex traits.
Area of Science:
- Genetics
- Genomics
- Molecular Biology
Background:
- Sequence-based variation in gene expression is a major contributor to disease risk.
- Expression quantitative trait locus (eQTL) studies have identified common variants regulating gene expression, primarily in cis and within single tissues.
- Existing research often overlooks the contribution of rare variants and multi-tissue analyses.
Purpose of the Study:
- To comprehensively analyze gene expression across multiple tissues in twins to dissect genetic and non-genetic effects.
- To quantify the contribution of common versus rare variants to cis-acting gene expression heritability.
- To identify trans-acting genetic variants influencing gene expression in a tissue-specific manner.
Main Methods:
- Analysis of gene expression data from a large cohort of monozygotic and dizygotic twins.
- Utilizing identity-by-descent (IBD) estimates to differentiate genetic effects.
- Systematic dissection of cis- and trans-acting genetic influences and non-genetic effects on gene expression.
Main Results:
- At least 40% of heritable cis effects on gene expression are not explained by common cis variants, highlighting the role of low-frequency and rare regulatory variants.
- A substantial proportion of gene expression heritability is mediated by trans-acting variants.
- Several trans variants were identified that act in a tissue-restricted manner, potentially regulating multiple genes.
Conclusions:
- Rare and low-frequency variants play a critical role in transcriptional regulation and complex trait susceptibility.
- Trans-acting genetic variants contribute significantly to the heritability of gene expression, often in a tissue-specific manner.
- This study provides a more complete understanding of the genetic architecture of gene expression variation across multiple tissues.
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