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To understand genes, pathways, and networks related to puberty, we characterized the transcriptome of two tissues: the pituitary gland and ovaries. Samples were harvested from pre- and postpubertal Brahman heifers (same age group). Brahman heifers (Bos indicus) are older at puberty compared with Bos taurus, a productivity issue. With RNA sequencing, we identified differentially expressed (DEx) genes and important transcription factors (TF) and predicted coexpression networks. The number of DEx genes detected in the pituitary gland was 284 (P < 0.05), and VWC2L was the most DEx gene (fold change = 4.12, P = 0.01). The gene VWC2L promotes bone mineralization through transforming growth factor-β (TGFβ) signaling. Further studies of the link between bone mineralization and puberty could target VWC2L. In ovaries, 3,871 genes were DEx (P < 0.05). Four highly DEx genes were noteworthy for their function: SLC6A13 (a γ-aminobutyric acid [GABA] transporter), OXT (oxytocin), and NPY (neuropeptide Y) and its receptor NPY2R. These genes had higher ovarian expression in postpubertal heifers. The GABA and its receptors and transporters were expressed in the ovaries of many mammals, suggesting a role for this pathway beyond the brain. The OXT pathway has been known to influence the timing of puberty in rats, via modulation of GnRH. The effects of NPY at the hypothalamus, pituitary gland, and ovaries have been documented. Neuropeptide Y and its receptors are known factors in the release of GnRH, similar to OXT and GABA, although their roles in ovarian tissue are less clear. Pathways previously related to puberty such as TGFβ signaling (P = 6.71 × 10-5), Wnt signaling (P = 4.1 × 10-2), and peroxisome proliferator-activated receptor (PPAR) signaling (P = 4.84 × 10-2) were enriched in our data set. Seven genes were identified as key TF in both tissues: HIC2, ZIC4, ZNF219, ZSCAN26, LHX1, OLIG1, and a novel gene. An ovarian subnetwork created with TF and significant ovarian DEx genes revealed five zinc fingers as regulators: ZNF507, ZNF12, ZNF512, ZNF184, and ZNF432. Recent work of hypothalamic gene expression also pointed to zinc fingers as TF for bovine puberty. Although some zinc fingers may be ubiquitously expressed, the identification of DEx genes in common across tissues points to key regulators of puberty. The hypothalamus and pituitary gland had eight DEx genes in common. The hypothalamus and ovaries had 89 DEx genes in common. The pituitary gland and ovaries had 48 DEx genes in common. Our study confirmed the complexity of puberty and suggested further investigation on genes that code zinc fingers. [ABSTRACT FROM AUTHOR]

Measures of heifer fertility are economi-cally 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 heif-ers (3/8 Brahman x 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 con-ception (FSC). These fertility traits were collected from controlled breeding seasons initiated with estrous syn-chronization and Al 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 associ-ated 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 hypothala-mus of a prepubertal and a postpubertal Brangus heifer. The remaining hypothalamic-influenced network con-tained 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. [ABSTRACT FROM AUTHOR]

The growth endocrine axis influences reproduction. The objectives of this study were to evaluate population genetic characteristics of SNP genotypes within genes of the GH-IGF axis in straightbred and crossbred Angus, Brahman, and Romosinuano heifers (n = 650) and to test the association of these genotypes with measures of reproduction. These objectives were achieved using 73 SNP within 7 genes on chromosome 5 and the pregnancy-associated plasma protein A2 (PAPP-A2) and GH-receptor genes, which map to chromosomes 16 and 20, respectively. The SNP were elucidated by resequencing conserved regions of each gene by using DNA from familial-unrelated cattle of a multibreed discovery population. A multiplex SNP assay yielded 59 biallelic SNP useful for evaluating genetic identity and distance. Specifically, the divergence of straightbred Brahman cattle was approximately 15.5% from 5 Bos taurus-influenced breed groups. In the straightbred groups used as a validation population, only 3 SNP had minor allele frequencies >10%. These SNP were in the genes PAPP-A2 (ss115492449-A/C and ss115492450-G/T within intron 10) and signal transducers and activators of transcription 2 (STAT2; ss252841035-A/G within the 5′ untranslated region), and they met the conditions of Hardy-Weinberg equilibrium (P > 0.31). The other 56 SNP were useful for assigning each animal into ancestral clusters (n = 3 proportions) to account for population stratification in genotype to phenotype association analyses. The 2 SNP in the PA PP-A 2 gene influenced (P < 0.05) traits indicative of first-calf heifer rebreeding (i.e., calving interval, days to calving, and pregnancy rate). A STAT2 SNP genotype (i.e., GG) × primary ancestral cluster interaction (P < 0.05) suggested heifers primarily of B. taurus ancestry had a reduction of approximately 16.4 + 0.1% in calving interval and days to calving relative to heifers clustering primarily as Bus indicus ancestry. Even though additional research is needed to delineate the allelic variation attributed to genes of the GH-IGF axis, results of this study provide support for STAT2 and PA PP-A2 as potential candidate genes associated with first-calf heifer rebreeding traits. [ABSTRACT FROM AUTHOR]

The objective was to identify single nucleotide polymorphisms (SNP) associated to fertility in cows raised under a subtropical environment. Re-sequencing of nine genes associated to GH-IGF endocrine pathway, which are located in bovine chromosomes 5, 16 and 20, identified 73 SNP useful for associative genetic studies; however, only seven resulted as polymorphic and unique to the Romosinuano breed. Then, DNA samples were extracted from 129 beef heifers and used to determine genotypes corresponding to each SNP. Mixed model analysis identified one SNP from the PAPP-A2 gene (C/T, rs110490898) as predictor (P<0.05) of reproductive performance. The allele T was the most favorable allele (P<0.05), because it was associated with lower age at first calving (-37.1 ± 14.4 d) and age at second calving (-65.43 ± 30.8 d). In the contrast analysis, the linear term resulted as significant and quadratic term as non significant, which suggested an additive effect of the alleles. These results provide evidence to support the PAPP-A2 gene as a candidate gene associated to reproductive performance in heifers and first-calf cows from the Romosinuano breed, raised under a subtropical environment. [ABSTRACT FROM AUTHOR]

El objetivo fue identificar polimorfismos de un solo nucleótido (SNP) asociados a la fertilidad en hembras bovinas criadas en subtropico. La re-secuenciación de nueve genes relacionados al eje endocrino GH-IGF, localizados en los cromosomas 5, 16 y 20 del bovino, identificó 73 SNP útiles para estudios genéticos asociativos; sin embargo, sólo siete resultaron polimórficos y exclusivos de la raza Romosinuano. Muestras de ADN se extrajeron de 129 vaquillas Romosinuano y usadas para determinar los genotipos correspondientes a cada SNP. Un análisis de modelos mixtos identificó únicamente a un polimorfismo del gen PAPP-A2 (C/T, rs110490898) como predictor (P<0.05) del comportamiento reproductivo. El alelo T fue el más favorable (P<0.05) ya que éste se asoció a una reducción tanto en la edad al primer parto (-37.1 ± 14.4 días), como en la edad al segundo parto (-65.43 ± 30.8 días). En el análisis de contrastes el término lineal resultó significativo (P<0.05), pero no el quadrático, lo cual sugiere un efecto aditivo de los alelos. Los resultados proporcionan evidencia para proponer al gen PAPP-A2, como candidato asociado al comportamiento reproductivo en vaquillas y vacas primerizas de la raza Romosinuano. [ABSTRACT FROM AUTHOR]