Single nucleotide polymorphisms in the growth hormone - insulin like growth factor axis in straight bred and crossbred Angus, Brahman, and Romosinuano heifers: population genetic analyses and association of genotypes

Authors: LUNA-NEVAREZ, PABLO - Ministry Of Science And Innovation, Csic; RINCON, GONZALO - University Of California; MEDRANO, JUAN - University Of California; RILEY, DAVID - Texas Agrilife Research; Chase, Chadwick - Chad; Coleman, Samuel; VANLEEUWEN, DAWN - New Mexico State University; DEATLEY, KASEY - New Mexico State University; ISLAS-TREJO, ALMA - University Of California; SILVER, GAIL - New Mexico State University; THOMAS, MILTON - New Mexico State University

Submitted to: Journal of Animal Science
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/10/2011
Publication Date: 4/1/2011
Citation: Luna-Nevarez, P., Rincon, G., Medrano, J., Riley, D.G., Chase, C.C., Coleman, S.W., Vanleeuwen, D., Deatley, K., Islas-Trejo, A., Silver, G., Thomas, M. 2011. Single nucleotide polymorphisms in the growth hormone - insulin like growth factor axis in straight bred and crossbred Angus, Brahman, and Romosinuano heifers: population genetic analyses and association of genotypes. Journal of Animal Science. 89:926-934.

Interpretive Summary: Brahman cattle, which are a Bos indicus breed, are slower to reach sexual maturity relative to Bos taurus breeds such as Angus and Romosinuano. Brahman-crossed cattle; however, experience heterosis or hybrid vigor for heifer and cow fertility traits, especially in subtropical and tropical production systems. The growth endocrine axis, primarily growth hormone (GH) and insulin-like growth factor (IGF) have been shown to influence reproductive processes. This endocrine axis has been intensively studied for its role in growth, lactation, and adiposity in domestic animals. Chromosome 5 harbors quantitative trait loci (QTL) that have been associated with fertility traits in cattle and the IGF-I gene map to this locus. There are at least 6 additional genes that underlie these QTL that are known to influence the endocrine and cell signaling pathways of GH and IGF. Likewise, there are numerous other genes and tissues involved in the growth endocrine axis. For example, pappalysin-2 encoded by the pregnancy associated plasma protein A2 (PAPP-A2) gene cleaves IGF binding protein (IGFBP) -4 and -5 from IGF-I and II. This gene maps to chromosome 16 and single nucleotide polymorphisms (SNP) in this gene are associated with fertility trait measures in Holstein cattle. Objectives of this study were to evaluate population genetic characteristics of SNP genotypes within genes of the GH and IGF axis in straightbred and diallel-crossed Angus, Brahman, and Romosinuano heifers (n = 650) and to test the association(s) of these genotypes and haplotypes with measures of reproduction. These objectives were achieved using 73 SNP within 7 genes on chromosome 5; and PAPP-A2 and GH-receptor genes that map to chromosomes 16 and 20, respectively. The multiplex SNP assay yielded 59 SNP useful for evaluating genetic identity and distance. Three SNP were useful (informative) among straightbreds and were in the genes of PAPP-A2 and signal transducers and activators of transcription 2 (STAT2). The two SNP in the PAPP-A2 gene significantly influenced traits indicative of 1st-calf heifer rebreeding (i.e., calving interval, days to calving, and pregnancy rate). Heifers that had two copies of one of these haplotypes had a 9.2% advantage over heifers with no copies for the 3 traits. The STAT2 SNP genotype interacted with ancestry cluster suggesting that predominately Bos taurus heifers had a 16% reduction in calving interval and days to calving relative to predominately Bos indicus heifers. Results of this study provide support for STAT2 and PAPP-A2 as positional candidate genes associated with 1st-calf heifer re-breeding traits.

Technical Abstract: The growth endocrine axis influences reproduction. Objectives of this study were to evaluate population genetic characteristics of SNP genotypes within genes of the GH and IGF axis in straightbred and diallel-crossed Angus, Brahman and Romosinuano heifers (n = 650) and to test the associations of these genotypes and haplotypes 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 discovered by re-sequencing conserved regions of each gene using DNA from multi-breed resource populations and familial-unrelated cattle. A multiplex SNP assay yielded 59 bi-allelic SNP useful for evaluating genetic identity and distance. Specifically, divergence of straightbred Brahman cattle was approximately 15.5% from 5 Bos taurus-influenced breed groups. Only 3 SNP had minor allele frequencies > 10% in the straightbred groups. These SNP were in the genes of 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). The SNP met the conditions of Hardy-Weinberg equilibrium (P > 0.31) and the 2 PAPP-A2 SNP were in linkage disequilibrium (P < 0.01). 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 PAPP-A2 gene influenced (P < 0.05) traits indicative of 1st-calf heifer rebreeding (i.e., calving interval, days to calving, and pregnancy rate). Analyses involving the most frequent haplotype (C-G) revealed similar results (P < 0.05) and heifers having 2 copies of this haplotype appeared to have a 9.2 ± 0.1% advantage over heifers with no copies for the 3 traits. A STAT2 SNP genotype (i.e., GG) x primary ancestral cluster interaction (P < 0.05) suggested heifers primarily of Bos taurus ancestry had approximately 16.4 ± 0.1% reduction in calving interval and days to calving relative to heifers clustering primarily as Bos 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 PAPP-A2 as positional candidate genes associated with 1st-calf heifer re-breeding traits.