Genome-wide association studies for heat stress response in Bos taurus × Bos indicus crossbred cattle

Abstract

Heat stress is an important issue in the global dairy industry. In tropical areas, an alternative to overcome heat stress is the use of crossbred animals or synthetic breeds, such as the Girolando. In this study, we performed a genome-wide association study (GWAS) and post-GWAS analyses for heat stress in an experimental Gir × Holstein F 2 population. Rectal temperature (RT) was measured in heat-stressed F 2 animals, and the variation between 2 consecutive RT measurements (ΔRT) was used as the dependent variable. Illumina BovineSNP50v1 BeadChip (Illumina Inc., San Diego, CA) and single-SNP approach were used for GWAS. Post-GWAS analyses were performed by gene ontology terms enrichment and gene-transcription factor (TF) networks, generated from enriched TF. The breed origin of marker alleles in the F 2 population was assigned using the breed of origin of alleles (BOA) approach. Heritability and repeatability estimates (± standard error) for ΔRT were 0.13 ± 0.08 and 0.29 ± 0.06, respectively. Association analysis revealed 6 SNP significantly associated with ΔRT. Genes involved with biological processes in response to heat stress effects (LIF, OSM, TXNRD2, and DGCR8) were identified as putative candidate genes. After performing the BOA approach, the 10% of F 2 animals with the lowest breeding values for ΔRT were classified as low-ΔRT, and the 10% with the highest breeding values for ΔRT were classified as high-ΔRT. On average, 49.4% of low-ΔRT animals had 2 alleles from the Holstein breed (HH), and 39% had both alleles from the Gir breed (GG). In high-ΔRT animals, the average proportion of animals for HH and GG were 1.4 and 50.2%, respectively. This study allowed the identification of candidate genes for ΔRT in Gir × Holstein crossbred animals. According to the BOA approach, Holstein breed alleles could be associated with better response to heat stress effects, which could be explained by the fact that Holstein animals are more affected by heat stress than Gir animals and thus require a genetic architecture to defend the body from the deleterious effects of heat stress. Future studies can provide further knowledge to uncover the genetic architecture underlying heat stress in crossbred cattle.

New loci and neuronal pathways for resilience to heat stress in animals

“…Third, differences in the patterns of LD among study populations used and imputation quality may have implications on GWAS, particularly in the detection of putative causal mutations [56]. Here we explored QTLs for heat tolerance in purebred Holstein cows, while some other studies, e.g., [16] have used crossbred cattle. Collectively, these factors likely impacted the replication of previous GWAS candidate genes for heat tolerance.…”

“…Several genome-wide association studies ( GWAS ) using Single nucleotide polymorphisms ( SNPs ) have been conducted over the last decade to identify candidate causal genes for various heat tolerance traits (rectal temperature, heart rate, sweating rate, rate of milk yield decline, etc.) in dairy cattle [13–16] and pigs [17]. However, these GWAS were underpowered, with the largest sample size to date of around 5,000 animals [13, 14].…”

New loci and neuronal pathways for resilience to heat stress in cattle

“…Identifying specific genetic variants that increase tolerance to heat may help to improve dairy breeding programmes in addition to improving our knowledge of the thermal biology in other mammals. However, except for mutations in the SLICK locus 11 , the identification of the specific genetic variants for heat tolerance in cattle and other species has, in most cases, remained elusive, in part due to many reasons, including the sample size used in past studies 12 – 15 .…”

Genomic analyses and biological validation of candidate genes for rectal temperature as an indicator of heat stress in Holstein cattle

“…Other GWAS have been performed based on other indicators of heat stress response. For instance, Otto et al (2019) performed GWAS and post-GWAS analyses for the variation between 2 consecutive RT measurements in a crossbreed population (Gir × Holstein). Genes involved with biological processes in response to heat stress effects (LIF, OSM, TXNRD2, and DGCR8) were identified as putative candidate genes.…”