Journal Article

Gene expression allelic imbalance in ovine brown adipose tissue impacts energy homeostasis

Nicholas, Lisa M., Yang, Jean Y. H., Morrison, Janna L., Ghazanfar, Shila, McMillen, Isabella C., Vuocolo, Tony, Buckley, Michael J., Tellam, Ross L.

2017

Overview

Heritable trait variation within a population of organisms is largely governed by DNA variations that impact gene transcription and protein function. Identifying genetic variants that affect complex functional traits is a primary aim of population genetics studies, especially in the context of human disease and agricultural production traits. The identification of alleles directly altering mRNA expression and thereby biological function is challenging due to difficulty in isolating direct effects of cis-acting genetic variations from indirect trans-acting genetic effects. Allele specific gene expression or allelic imbalance in gene expression (AI) occurring at heterozygous loci provides an opportunity to identify genes directly impacted by cis-acting genetic variants as indirect trans-acting effects equally impact the expression of both alleles. However, the identification of genes showing AI in the context of the expression of all genes remains a challenge due to a variety of technical and statistical issues. The current study focuses on the discovery of genes showing AI using single nucleotide polymorphisms as allelic reporters. By developing a computational and statistical process that addressed multiple analytical challenges, we ranked 5,809 genes for evidence of AI using RNA-Seq data derived from brown adipose tissue samples from a cohort of late gestation fetal lambs and then identified a conservative subgroup of 1,293 genes. Thus, AI was extensive, representing approximately 25% of the tested genes. Genes associated with AI were enriched for multiple Gene Ontology (GO) terms relating to lipid metabolism, mitochondrial function and the extracellular matrix. These functions suggest that cis-acting genetic variations causing AI in the population are preferentially impacting genes involved in energy homeostasis and tissue remodelling. These functions may contribute to production traits likely to be under genetic selection in the population.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adipose tissue / Adipose tissue (brown) / Adipose Tissue, Brown - metabolism / Agricultural production / Alleles / Allelic Imbalance / Animals / Bias / Biological effects / Biology and Life Sciences / Body fat / Computer applications / Deoxyribonucleic acid / DNA / Energy balance / Enrichment / Epigenetics / Extracellular matrix / Female / Fetuses / Gene expression / Genes / Genetic aspects / Genetic diversity / Genetic effects / Genetic variance / Genetic variation / Genetics / Genomes / Genomics / Gestation / Homeostasis / Humans / Knowledge representation / Lipid metabolism / Mammals / Mathematical analysis / Medical research / Medicine and Health Sciences / Messenger RNA / Metabolism / Mitochondria / Pharmacy / Polymorphism, Single Nucleotide / Population / Population (statistical) / Population genetics / Population studies / Pregnancy / Ribonucleic acid / RNA / Sheep / Single nucleotide polymorphisms / Single-nucleotide polymorphism / Statistical analysis / Statistical methods / Statistics / Transcription