gBLUP-GWAS identifies candidate genes, signaling pathways, and putative functional polymorphisms for age at puberty in gilts

Authors: WIJESENA, HIRUNI - Orise Fellow; Nonneman, Danny - Dan; Snelling, Warren; Rohrer, Gary; Keel, Brittney; Lents, Clay

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/21/2023
Publication Date: 2/27/2023
Citation: Wijesena, H.R., Nonneman, D.J., Snelling, W.M., Rohrer, G.A., Keel, B.N., Lents, C.A. 2023. gBLUP-GWAS identifies candidate genes, signaling pathways, and putative functional polymorphisms for age at puberty in gilts. Journal of Animal Science. Article skad063. https://doi.org/10.1093/jas/skad063.
DOI: https://doi.org/10.1093/jas/skad063

Interpretive Summary: Selecting for replacement gilts is challenging because sow reproductive traits are lowly heritable and expressed late in life. Age at puberty is the earliest indicator of future reproductive success of gilts, but genetic selection for early onset of puberty is limited due to lack of molecular genetic predictors. Scientists at Clay Center, Nebraska, conducted a large-scale genome-wide association study to identify genomic regions associated with variation in age at puberty in gilts. They identified both previously known and new novel genomic associations. Several candidate genes identified within these genomic regions are involved in hormone secretion and ovarian function. These data provide important new markers for use in swine breeding programs to select replacement gilts, and that will be further evaluated their involvement in regulating additional sow fertility traits.

Technical Abstract: Successful development of replacement gilts determines their reproductive longevity and lifetime productivity. Selection for reproductive longevity is challenging due to low heritability and expression late in life. In pigs, age at puberty is the earliest known indicator for reproductive longevity and gilts that reach puberty earlier have a greater probability of producing more lifetime litters. Failure of guilts to reach puberty and display a pubertal estrus is a major reason for early removal of replacement gilts. To identify genomic sources of variation in age at puberty for improving genetic selection for early age at puberty and related traits, gilts (n = 4,986) from a multigeneration population representing commercially available maternal genetic lines were used for a genomic best linear unbiased prediction-based genome-wide association. Twenty-one genome-wide significant single nucleotide polymorphisms (SNP) located on Sus scrofa chromosomes (SSC) 1, 2, 9, and 14 were identified with additive effects ranging from -1.61 to 1.92 d (P < 0.0001 to 0.0671). Novel candidate genes and signaling pathways were identified for age at puberty. The locus on SSC9 (83.7 to 86.7 Mb) was characterized by long range linkage disequilibrium and harbors the AHR transcription factor gene. A second candidate gene on SSC2 (82.7 Mb), ANKRA2, is a corepressor for AHR, suggesting a possible involvement of AHR signaling in regulating pubertal onset in pigs. Putative functional SNP associated with age at purberty in the AHR and ANKRA2 genes were identified. Combined analysis of these SNP showed that an increase in the number of favorable alleles reduced pubertal age by -5.84 ± 1.65 d (P < 0.001). Candidate genes for age at puberty showed pleiotropic effects with other fertility functions such as gonadotropin secretion (FOXD1), follicular development (BMP4), pregnancy (LIF), and litter size (MEF2C). Several candidate genes and signaling pathways identified in this study play a physiological role in the hypothalamic-pituitary-gonadal axis and mechanisms permitting puberty onset. Variants located in or near these genes require further characterization to identify their impact on pubertal onset in gilts. Because age at puberty is an indicator of future reproductive success, these SNP are expected to improve the genomic prediction for component traits of sow fertility and lifetime productivity expressed later in life.