Gene Network Analyses of First Service Conception in Brangus Heifers: Use of Genome and Trait Associations, Hypothalamic-Transcriptome Information, and Transcription Factors

Measures of heifer fertility are economically relevant traits for beef production systems and knowledge of candidate genes is useful in genomic selection strategies. Ten traits related to growth and fertility were measured in 890 Brangus heifers (3/8 Brahman x 5/8 Angus), which included first service conception (FSC). The BovineSNP50 BeadChip was used to ascertain SNP genotypes and genome-wide association studies (GWAS) were performed for the 10 traits. These associations and SNP effects were used in an association weight matrix to derive a gene network related to FSC. In the network, 1,386 SNP inferred genes that were nodes connected through 5,132 significant correlations (r ≥ 0.90) that were edges. This 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 pre- and a post-pubertal 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. There were five transcription factors with 21 or more connections for FSC: ZMAT3, STAT6, RFX4, PLAGL1, and NR6A. The SNP that identified these genes were intragenic and were on chromosomes 1, 5, 9, and 11. Chromosome five 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 as a polygenic trait.