Allele-specific expression is widespread in Bos indicus muscle and affects meat quality candidate genes

Marcela Maria De Souza,Mauricio De Alvarenga Mudadu,Fabiana Barichello Mokry,Wellison Jarles Da Silva Diniz,Luiz Lehmann Coutinho,Priscila Silva Neubern De Oliveira,Marina Ibelli Pereira Rocha,Tainã Figueiredo Cardoso,Simone Cristina Méo Niciura,Luciana Correia De Almeida Regitano,Jennifer Jessica Bruscadin,Bruno Gabriel Nascimento Andrade,Polyana Cristine Tizioto,Adhemar Zerlotini,Juliana Afonso,Aline Silva Mello Cesar

doi:10.1038/s41598-020-67089-0

Abstract

Differences between the expression of the two alleles of a gene are known as allele-specific expression (ASE), a common event in the transcriptome of mammals. Despite ASE being a source of phenotypic variation, its occurrence and effects on genetic prediction of economically relevant traits are still unexplored in bovines. Furthermore, as ASE events are likely driven by cis-regulatory mutations, scanning them throughout the bovine genome represents a significant step to elucidate the mechanisms underlying gene expression regulation. To address this question in a Bos indicus population, we built the ASE profile of the skeletal muscle tissue of 190 Nelore steers, using RNA sequencing data and SNPs genotypes from the Illumina BovineHD BeadChip (770 K bp). After quality control, 820 SNPs showed at least one sample with ASE. These SNPs were widespread among all autosomal chromosomes, being 32.01% found in 3′UTR and 31.41% in coding regions. We observed a considerable variation of ASE profile among individuals, which highlighted the need for biological replicates in ASE studies. Functional analysis revealed that ASE genes play critical biological functions in the development and maintenance of muscle tissue. Additionally, some of these genes were previously reported as associated with beef production and quality traits in livestock, thus indicating a possible source of bias on genomic predictions for these traits.

Highlights

The mechanisms that regulate gene expression are relevant sources of phenotypic variation among individuals
Specific genomic regions can control the expression of some genes, acting intrinsically or in response to environmental stimuli. These regulatory elements are known as expression quantitative trait loci and can be classified either as cis, when they affect the expression of adjacent genes on the same DNA molecule, or as trans, when they affect physically distant genes
Given that the imbalanced allelic expression usually indicates that a cis-regulation of the gene expression is taking place, allele-specific expression (ASE) analysis is used for detecting cis-regulatory elements, as cis-expression quantitative trait loci (eQTL), complementing traditional methods of genetic linkage studies[8]

Summary

Introduction

The mechanisms that regulate gene expression are relevant sources of phenotypic variation among individuals. Given that the imbalanced allelic expression usually indicates that a cis-regulation of the gene expression is taking place, ASE analysis is used for detecting cis-regulatory elements, as cis-eQTLs, complementing traditional methods of genetic linkage studies[8]. ASE has been used as a starting point for several studies, such as aseQTL, in which sequence variations correlated with unequal allele expression are identified, complementing the eQTL studies[3,6,8,10] They are useful for mapping interaction effects between genotype and environment, known as response expression quantitative trait loci (reQTL)[11]. ASE data can be integrated with DNA methylation, providing insights to the effects of methylation on the allelic expression, supporting imprinted gene discovery and parental origin effect determination[12]

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Results

Conclusion