Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/2/2012
Publication Date: 9/1/2012
Citation: Fortes, M., Snelling, W.M., Reverter, A., Nagaraj, S.H., Lehnert, S.A., Hawken, R.J., Deatley, K.L., Peters, S.O., Silver, G.A., Rincon, G., Medrano, J.F., Islas-Trejo, A., Thomas, M.G. 2012. Gene network analyses of first service conception in Brangus heifers: Use of genome and trait associations, hypothalamic-transcriptome information, and transcription factors. Journal of Animal Science. 90(9):2894-2906. Interpretive Summary: Heifer fertility influences profitability of cow-calf production. Identifying genes affecting heifer fertility may enable genomic selection to focus on those genes, allowing more rapid improvement than that possible through phenotypic selection for lowly heritable traits like heifer pregnancy or first service conception. Associations between genotypes for approximately 50,000 genetic markers and first service conception, pregnancy, and traits reflecting heifer growth and body composition, measured on approximately 800 Brangus heifers, were used to define a network of genes associated with heifer fertility. Hypothalmus transcriptomes of prepubertal and postpubertal Brangus heifers provided information about which of these genes were expressed, resulting in a network of 978 interacting genes. The hypolthalmic gene network was enriched with genes involved in axon guidance, a pathway known to influence pulsatile release of luteinizing hormone-releasing hormone, which is an important factor in endocrine control of puberty and reproduction. Interactions among genes in the network were supported by identification of key transcription factors, each affecting expression of at least 20 network genes. The number of genes involved in the network associated with first service conception, and other traits related to heifer development and fertility, suggests the traits are indeed polygenic, so that genomic selection for heifer fertility will need to consider many loci.
Technical Abstract: Measures of heifer fertility are economically relevant traits for beef production systems and knowledge of candidate genes could be incorporated into future genomic selection strategies. Ten traits related to growth and fertility were measured in 890 Brangus heifers (3/8 Brahman × 5/8 Angus, from 67 sires). These traits were: BW and hip height adjusted to 205 and 365 d of age, postweaning ADG, yearling assessment of carcass traits (i.e., back fat thickness, intramuscular fat, and LM area), as well as heifer pregnancy and first service conception (FSC). These fertility traits were collected from controlled breeding seasons initiated with estrous synchronization and AI targeting heifers to calve by 24 mo of age. The BovineSNP50 BeadChip was used to ascertain 53,692 SNP genotypes for ~802 heifers. Associations of genotypes and phenotypes were performed and SNP effects were estimated for each trait. Minimally associated SNP (P < 0.05) and their effects across the 10 traits formed the basis for an association weight matrix and its derived gene network related to FSC (57.3% success and heritability = 0.06 ± 0.05). These analyses yielded 1,555 important SNP, which inferred genes linked by 113,873 correlations within a network. Specifically, 1,386 SNP were nodes and the 5,132 strongest correlations (|r| = 0.90) were edges. The network was filtered with genes queried from a transcriptome resource created from deep sequencing of RNA (i.e., RNA-Seq) from the hypothalamus of a prepubertal and a postpubertal Brangus heifer. The remaining hypothalamic-influenced network contained 978 genes connected by 2,560 edges or predicted gene interactions. This hypothalamic gene network was enriched with genes involved in axon guidance, which is a pathway known to influence pulsatile release of LHRH. There were 5 transcription factors with 21 or more connections: ZMAT3, STAT6, RFX4, PLAGL1, and NR6A1 for FSC. The SNP that identified these genes were intragenic and were on chromosomes 1, 5, 9, and 11. Chromosome 5 harbored both STAT6 and RFX4. The large number of interactions and genes observed with network analyses of multiple sources of genomic data (i.e., GWAS and RNA-Seq) support the concept of FSC being a polygenic trait.