Potential functional variants in AHR signaling pathways are associated with age at puberty in swine

Abstract

Puberty in female pigs is defined as age at first estrus and gilts that have an earlier age at puberty are more likely to have greater lifetime productivity. Because age at puberty is predictive for sow longevity and lifetime productivity, but not routinely measured in commercial herds, it would be beneficial to use genomic or marker-assisted selection to improve these traits. A GWAS at the US Meat Animal Research Center (USMARC) identified several loci associated with age at puberty in pigs. Candidate genes in these regions were scanned for potential functional variants using sequence information from the USMARC swine population founder animals and public databases. In total, 135 variants (SNP and insertion/deletions) in 39 genes were genotyped in 1284 phenotyped animals from a validation population sired by Landrace and Yorkshire industry semen using the Agena MassArray system. Twelve variants in eight genes were associated with age at puberty (P < 0.005) with estimated additive SNP effects ranging from 1.6 to 5.3 days. Nine of these variants were non-synonymous coding changes in AHR, CYP1A2, OR2M4, SDCCAG8, TBC1D1 and ZNF608, two variants were deletions of one and four codons in aryl hydrocarbon receptor, AHR, and the most significant SNP was near an acceptor splice site in the acetyl-CoA carboxylase alpha, ACACA. Several of the loci identified have a physiological and a genetic role in sexual maturation in humans and other animals and are involved in AHR-mediated pathways. Further functional validation of these variants could identify causative mutations that influence age at puberty in gilts and possibly sow lifetime productivity.

Analysis of merged transcriptomic and genomic datasets to identify genes and pathways underlying residual feed intake in growing pigs

“…In this way, one of the transcription factor coding genes located in QTL-1, AHR, can explain the differential expression of 65 DE genes. The AHR gene has been considered a candidate gene for reproductive traits in previous studies (37)(38)(39). SNP calling based on RNA-seq data revealed four missense mutations in the protein-coding part of the AHR gene.…”

Analysis of merged transcriptomic and genomic datasets to identify genes and pathways underlying residual feed intake in growing pigs

“…In this way, a transcription factor encoding gene located in QTL-1, AHR, may explain the differential expression of nine out of 17 DE-genes. The AHR gene has to our knowledge not been linked to FE before, but it has been considered a candidate gene for reproductive traits in previous studies [31][32][33] . SNP calling based on RNA-seq data revealed four missense mutations in the protein-coding part of the AHR gene.…”

Functional genomics of reproduction in pigs: Are we there yet?

“…In D. Nonneman et al (2021), 94 potential functional variants (SNP and insertion/deletions) in 33 genes identified from a previous GWAS (D. J. Nonneman et al, 2016) were analyzed for association with age at puberty. Ten variants in six genes were found to be significantly associated with age at puberty in a validation population.…”

“…In D. Nonneman et al (2021), 94 potential functional variants (SNP and insertion/deletions) in 33 genes identified from a previous GWAS (D. J. Nonneman et al, 2016) were analyzed for association with age at puberty.…”

“…However, the most compelling associations with potential functional variants and age at puberty were found the aryl hydrocarbon receptor ( AHR ) and the cytochrome P‐450 CYP1A2 genes. Of the five nonsynonymous SNPs and two indels in AHR and seven SNP in CYP1A2 analyzed; three SNP and the two indels in the transactivation domain of AHR and one nonsynonymous SNP in CYP1A2 were significantly associated with age at puberty (D. Nonneman et al, 2021). Activation of AHR by endogenous or xenobiotic ligands causes induction of the cytochrome P450 enzymes CYP1A1 , CYP1A2 , and CYP1B1 , which have high activity for metabolism of estrogenic compounds.…”