Gene function & annotation

Integrative Cis-Expression Quantitative Trait Loci Mapping and Mediation Analysis Reveals Regulatory Genes Influencing Feed Intake and Growth in Lambs.

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Abstract

Understanding the genetic regulation of feed efficiency (FE) and growth is critical for improving livestock production. Dry matter intake (DMI) and Average daily live weight gain (ADG) are important FE indicators, reflecting feed consumption and growth. Expression quantitative trait loci (eQTL) connect genetic variants to transcriptional changes, providing a better understanding into the causative pathways affecting complex traits. However, such studies in sheep are limited, particularly those that investigate how genetic variation influences gene expression, thereby contributing to FE variations. This study aimed to identify cis-regulatory variants and evaluate whether gene expression mediates the effects of genetic variants on sheep FE. Twenty-eight male weaned lambs (Texel x mule) with matched genotype and RNA-Seq data were analysed. Normalized gene expression matrix and high-quality single nucleotide polymorphism (SNP) genotypes were used as input into the MatrixeQTL software using a linear model with a ±1 Mb cis window. Cis-eQTLs (SNP-level) were identified and filtered based on multiple testing using Benjamini-Hochberg (BH) method (False discovery rate (FDR) P 0.03) with strongest signals observed on genes such as PLPPR1, NOX4, and LOC121816523 in both methods. A notable concordance of 77 genes were observed from SNP-level and gene-level analyses revealing true evidence for cis-regulatory roles. Mediation analysis of these genes revealed significant ACME effects on 19 SNPs associated with 14 genes including PLPPR1 (phospholipid metabolism), COL13A1, COL5A1 (connective tissue structure, muscle organization), STN1 (telomere length maintenance), RAD51D (DNA repair), RHPN1 (organization of cytoskeleton), RELL1, NOX4 (oxidative signalling), and several uncharacterized genes, demonstrating that gene expression partially mediates genetic effects on DMI and ADG. Interestingly, PLPPR1 significantly mediated the effects of their respective SNPs on both DMI and ADG (ACME, P < 0.05). Mediation effects of several uncharacterized genes in this study suggests novel regulatory pathways contributing to growth, warranting further research. Findings from this study shows that genetic variants influence FE through cis-regulatory effects on gene expression. This integrative analysis highlights the importance of combining genotype, RNA-Seq, and phenotype data to reveal causal mechanisms underlying complex traits, even with limited sample sizes. These results provide insights into the complex trait variations and highlight the identified genes as candidates for application in functional studies or genomic selection programs, demonstrating the power of integrative genomics in livestock improvement.

Keywords: 2026

How to Cite:

Chacko Kaitholil, S., Mooney, M., Aubry, A., Razban, V., Rezwan, F. & Shirali, M., (2026) “Integrative Cis-Expression Quantitative Trait Loci Mapping and Mediation Analysis Reveals Regulatory Genes Influencing Feed Intake and Growth in Lambs.”, World Congress on Genetics Applied to Livestock Production Digital Archive 2026(1): 2285402. doi: https://doi.org/10.31274/wcgalp.23684

Rights: 1