Gene network analyses of first service conception in Brangus heifers: Use of genome and trait associations, hypothalamic-transcriptome information, and transcription factors1

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.

Heifer fertility and carry over consequences for life time production in dairy and beef cattle

“…Fortes et al (2012) measured 10 growth, carcass and fertility traits in 890 Brangus heifers and looked for associations using the 50K bovine SNP chip, with a particular focus on genes expressed in the hypothalamus which might be associated with puberty and first service conception rate. This identified a number of genes on BTA 1, 5, 9 and 11, leading the authors to conclude that heifer fertility was a polygenic trait.…”

BREEDING AND GENETICS SYMPOSIUM: Networks and pathways to guide genomic selection1–3

“…Overrepresentation analysis of the AWM genes also revealed biological processes relevant to puberty that were not implicated by single-trait GWAS and gene set analysis of age at fi rst corpus luteum. In a study of Brangus heifers, Fortes et al (2012) extended the AWM approach to include evidence of gene expression, fi ltering the initial 10-trait AWM by genes expressed in the hypothalamus transcriptome of pre-and postpubertal heifers to obtain a 978 gene network. Imputed genotypes of BovineHD SNP in the Brangus AWM genes accounted for at least one-half of the heritable variation in age at puberty, antral follicle count, and pregnancy rate of crossbred Bos taurus heifers .…”

Study of lipid metabolism-related genes as candidate genes of sexual precocity in Nellore cattle

“…In addition, this trait is difficult to select mainly because it is expressed only in females already at the onset of reproductive activity. Therefore, several studies have sought to identify molecular markers for early pregnancy (Hastings et al, 2006;Islam et al, 2009;Fortes et al, 2012).…”