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Seasonal shedding of winter hair at the start of summer is well studied in wild and domesticated populations. However, the genetic influences on this trait and their interactions are poorly understood. We use data from 13,364 cattle with 36,899 repeated phenotypes to investigate the relationship between hair shedding and environmental variables, single nucleotide polymorphisms, and their interactions to understand quantitative differences in seasonal shedding. Using deregressed estimated breeding values from a repeated records model in a genome-wide association analysis (GWAA) and meta-analysis of year-specific GWAA gave remarkably similar results. These GWAA identified hundreds of variants associated with seasonal hair shedding. There were especially strong associations between chromosomes 5 and 23. Genotype-by-environment interaction GWAA identified 1,040 day length-by-genotype interaction associations and 17 apparent temperature-by-genotype interaction associations with hair shedding, highlighting the importance of day length on hair shedding. Accurate genomic predictions of hair shedding were created for the entire dataset, Angus, Hereford, Brangus, and multibreed datasets. Loci related to metabolism and light-sensing have a large influence on seasonal hair shedding. This is one of the largest genetic analyses of a phenological trait and provides insight into both agriculture production and basic science., Competing Interests: Conflicts of interest Jared Decker and James Koltes were previously on the scientific advisory board of Vytelle, LLC., (© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America.)

Background: Genotypic information produced from single nucleotide polymorphism (SNP) arrays has routinely been used to identify genomic regions associated with complex traits in beef and dairy cattle. Herein, we assembled a dataset consisting of 15,815 Red Angus beef cattle distributed across the continental U.S. and a union set of 836,118 imputed SNPs to conduct genome-wide association analyses (GWAA) for growth traits using univariate linear mixed models (LMM); including birth weight, weaning weight, and yearling weight. Genomic relationship matrix heritability estimates were produced for all growth traits, and genotype-by-environment (GxE) interactions were investigated., Results: Moderate to high heritabilities with small standard errors were estimated for birth weight (0.51 ± 0.01), weaning weight (0.25 ± 0.01), and yearling weight (0.42 ± 0.01). GWAA revealed 12 pleiotropic QTL (BTA6, BTA14, BTA20) influencing Red Angus birth weight, weaning weight, and yearling weight which met a nominal significance threshold (P ≤ 1e-05) for polygenic traits using 836K imputed SNPs. Moreover, positional candidate genes associated with Red Angus growth traits in this study (i.e., LCORL, LOC782905, NCAPG, HERC6, FAM184B, SLIT2, MMRN1, KCNIP4, CCSER1, GRID2, ARRDC3, PLAG1, IMPAD1, NSMAF, PENK, LOC112449660, MOS, SH3PXD2B, STC2, CPEB4) were also previously associated with feed efficiency, growth, and carcass traits in beef cattle. Collectively, 14 significant GxE interactions were also detected, but were less consistent among the investigated traits at a nominal significance threshold (P ≤ 1e-05); with one pleiotropic GxE interaction detected on BTA28 (24 Mb) for Red Angus weaning weight and yearling weight., Conclusions: Sixteen well-supported QTL regions detected from the GWAA and GxE GWAA for growth traits (birth weight, weaning weight, yearling weight) in U.S. Red Angus cattle were found to be pleiotropic. Twelve of these pleiotropic QTL were also identified in previous studies focusing on feed efficiency and growth traits in multiple beef breeds and/or their composites. In agreement with other beef cattle GxE studies our results implicate the role of vasodilation, metabolism, and the nervous system in the genetic sensitivity to environmental stress., (© 2022. The Author(s).)

Understanding genotype-by-environment interactions (G × E) is crucial to understand environmental adaptation in mammals and improve the sustainability of agricultural production. Here, we present an extensive study investigating the interaction of genome-wide SNP markers with a vast assortment of environmental variables and searching for SNPs controlling phenotypic variance (vQTL) using a large beef cattle dataset. We showed that G × E contribute 10.1%, 3.8%, and 2.8% of the phenotypic variance of birth weight, weaning weight, and yearling weight, respectively. G × E genome-wide association analysis (GWAA) detected a large number of G × E loci affecting growth traits, which the traditional GWAA did not detect, showing that functional loci may have non-additive genetic effects regardless of differences in genotypic means. Further, variance-heterogeneity GWAA detected loci enriched with G × E effects without requiring prior knowledge of the interacting environmental factors. Functional annotation and pathway analysis of G × E genes revealed biological mechanisms by which cattle respond to changes in their environment, such as neurotransmitter activity, hypoxia-induced processes, keratinization, hormone, thermogenic and immune pathways. We unraveled the relevance and complexity of the genetic basis of G × E underlying growth traits, providing new insights into how different environmental conditions interact with specific genes influencing adaptation and productivity in beef cattle and potentially across mammals.

Background: Single nucleotide polymorphism (SNP) arrays have facilitated discovery of genetic markers associated with complex traits in domestic cattle; thereby enabling modern breeding and selection programs. Genome-wide association analyses (GWAA) for growth traits were conducted on 10,837 geographically diverse U.S. Gelbvieh cattle using a union set of 856,527 imputed SNPs. Birth weight (BW), weaning weight (WW), and yearling weight (YW) were analyzed using GEMMA and EMMAX (via imputed genotypes). Genotype-by-environment (GxE) interactions were also investigated., Results: GEMMA and EMMAX produced moderate marker-based heritability estimates that were similar for BW (0.36-0.37, SE = 0.02-0.06), WW (0.27-0.29, SE = 0.01), and YW (0.39-0.41, SE = 0.01-0.02). GWAA using 856K imputed SNPs (GEMMA; EMMAX) revealed common positional candidate genes underlying pleiotropic QTL for Gelbvieh growth traits on BTA6, BTA7, BTA14, and BTA20. The estimated proportion of phenotypic variance explained (PVE) by the lead SNP defining these QTL (EMMAX) was larger and most similar for BW and YW, and smaller for WW. Collectively, GWAAs (GEMMA; EMMAX) produced a highly concordant set of BW, WW, and YW QTL that met a nominal significance level (P ≤ 1e-05), with prioritization of common positional candidate genes; including genes previously associated with stature, feed efficiency, and growth traits (i.e., PLAG1, NCAPG, LCORL, ARRDC3, STC2). Genotype-by-environment QTL were not consistent among traits at the nominal significance threshold (P ≤ 1e-05); although some shared QTL were apparent at less stringent significance thresholds (i.e., P ≤ 2e-05)., Conclusions: Pleiotropic QTL for growth traits were detected on BTA6, BTA7, BTA14, and BTA20 for U.S. Gelbvieh beef cattle. Seven QTL detected for Gelbvieh growth traits were also recently detected for feed efficiency and growth traits in U.S. Angus, SimAngus, and Hereford cattle. Marker-based heritability estimates and the detection of pleiotropic QTL segregating in multiple breeds support the implementation of multiple-breed genomic selection.

Background: Single nucleotide polymorphism (SNP) arrays for domestic cattle have catalyzed the identification of genetic markers associated with complex traits for inclusion in modern breeding and selection programs. Using actual and imputed Illumina 778K genotypes for 3887 U.S. beef cattle from 3 populations (Angus, Hereford, SimAngus), we performed genome-wide association analyses for feed efficiency and growth traits including average daily gain (ADG), dry matter intake (DMI), mid-test metabolic weight (MMWT), and residual feed intake (RFI), with marker-based heritability estimates produced for all traits and populations., Results: Moderate and/or large-effect QTL were detected for all traits in all populations, as jointly defined by the estimated proportion of variance explained (PVE) by marker effects (PVE ≥ 1.0%) and a nominal P-value threshold (P ≤ 5e-05). Lead SNPs with PVE ≥ 2.0% were considered putative evidence of large-effect QTL (n = 52), whereas those with PVE ≥ 1.0% but < 2.0% were considered putative evidence for moderate-effect QTL (n = 35). Identical or proximal lead SNPs associated with ADG, DMI, MMWT, and RFI collectively supported the potential for either pleiotropic QTL, or independent but proximal causal mutations for multiple traits within and between the analyzed populations. Marker-based heritability estimates for all investigated traits ranged from 0.18 to 0.60 using 778K genotypes, or from 0.17 to 0.57 using 50K genotypes (reduced from Illumina 778K HD to Illumina Bovine SNP50). An investigation to determine if QTL detected by 778K analysis could also be detected using 50K genotypes produced variable results, suggesting that 50K analyses were generally insufficient for QTL detection in these populations, and that relevant breeding or selection programs should be based on higher density analyses (imputed or directly ascertained)., Conclusions: Fourteen moderate to large-effect QTL regions which ranged from being physically proximal (lead SNPs ≤ 3Mb) to fully overlapping for RFI, DMI, ADG, and MMWT were detected within and between populations, and included evidence for pleiotropy, proximal but independent causal mutations, and multi-breed QTL. Bovine positional candidate genes for these traits were functionally conserved across vertebrate species.

We conducted a genome-wide scan for visceral leishmaniasis in mixed-breed dogs from a highly endemic area in Brazil using 149,648 single nucleotide polymorphism (SNP) markers genotyped in 20 cases and 28 controls. Using a mixed model approach, we found two candidate loci on canine autosomes 1 and 2. The positional association on chromosome 2 mapped to a predicted DNAse sensitive site in CD14+ monocytes that serve as a cis-regulatory element for the expression of interleukin alpha receptors 2 (IL2RA) and 15 (IL15RA). Both interleukins were previously found to lead to protective T helper 1 cell (Th1) response against Leishmania spp. in humans and mice. The associated marker on chromosome 1 was located between two predicted transcription factor binding sites regulating the expression of the transducin-like enhancer of split 1 gene (TLE1), an important player in Notch signaling. This pathway is critical for macrophage activity and CD4+ T cell differentiation into Th1 and T helper 2. Together, these findings suggest that the human and mouse model for protective response against Leishmania spp., which involves Th1 and macrophage modulation by interleukins 2, 15, gamma interferon and Notch signaling, may also hold for the canine model.

Background: Beef cattle require dietary minerals for optimal health, production and reproduction. Concentrations of minerals in tissues are at least partly genetically determined. Mapping genomic regions that affect the mineral content of bovine longissimus dorsi muscle can contribute to the identification of genes that control mineral balance, transportation, absorption and excretion and that could be associated to metabolic disorders., Methods: We applied a genome-wide association strategy and genotyped 373 Nelore steers from 34 half-sib families with the Illumina BovineHD BeadChip. Genome-wide association analysis was performed for mineral content of longissimus dorsi muscle using a Bayesian approach implemented in the GenSel software., Results: Muscle mineral content in Bos indicus cattle was moderately heritable, with estimates ranging from 0.29 to 0.36. Our results suggest that variation in mineral content is influenced by numerous small-effect QTL (quantitative trait loci) but a large-effect QTL that explained 6.5% of the additive genetic variance in iron content was detected at 72 Mb on bovine chromosome 12. Most of the candidate genes present in the QTL regions for mineral content were involved in signal transduction, signaling pathways via integral (also called intrinsic) membrane proteins, transcription regulation or metal ion binding., Conclusions: This study identified QTL and candidate genes that affect the mineral content of skeletal muscle. Our findings provide the first step towards understanding the molecular basis of mineral balance in bovine muscle and can also serve as a basis for the study of mineral balance in other organisms.

The Bovine Respiratory Disease Coordinated Agricultural Project (BRD CAP) is a 5-year project funded by the United States Department of Agriculture (USDA), with an overriding objective to use the tools of modern genomics to identify cattle that are less susceptible to BRD. To do this, two large genome wide association studies (GWAS) were conducted using a case:control design on preweaned Holstein dairy heifers and beef feedlot cattle. A health scoring system was used to identify BRD cases and controls. Heritability estimates for BRD susceptibility ranged from 19 to 21% in dairy calves to 29.2% in beef cattle when using numerical scores as a semi-quantitative definition of BRD. A GWAS analysis conducted on the dairy calf data showed that single nucleotide polymorphism (SNP) effects explained 20% of the variation in BRD incidence and 17-20% of the variation in clinical signs. These results represent a preliminary analysis of ongoing work to identify loci associated with BRD. Future work includes validation of the chromosomal regions and SNPs that have been identified as important for BRD susceptibility, fine mapping of chromosomes to identify causal SNPs, and integration of predictive markers for BRD susceptibility into genetic tests and national cattle genetic evaluations.

We performed a genome-wide association study for Warner-Bratzler shear force (WBSF), a measure of meat tenderness, by genotyping 3360 animals from five breeds with 54 790 BovineSNP50 and 96 putative single-nucleotide polymorphisms (SNPs) within μ-calpain [HUGO nomenclature calpain 1, (mu/I) large subunit; CAPN1] and calpastatin (CAST). Within- and across-breed analyses estimated SNP allele substitution effects (ASEs) by genomic best linear unbiased prediction (GBLUP) and variance components by restricted maximum likelihood under an animal model incorporating a genomic relationship matrix. GBLUP estimates of ASEs from the across-breed analysis were moderately correlated (0.31-0.66) with those from the individual within-breed analyses, indicating that prediction equations for molecular estimates of breeding value developed from across-breed analyses should be effective for genomic selection within breeds. We identified 79 genomic regions associated with WBSF in at least three breeds, but only eight were detected in all five breeds, suggesting that the within-breed analyses were underpowered, that different quantitative trait loci (QTL) underlie variation between breeds or that the BovineSNP50 SNP density is insufficient to detect common QTL among breeds. In the across-breed analysis, CAPN1 was followed by CAST as the most strongly associated WBSF QTL genome-wide, and associations with both were detected in all five breeds. We show that none of the four commercialized CAST and CAPN1 SNP diagnostics are causal for associations with WBSF, and we putatively fine-map the CAPN1 causal mutation to a 4581-bp region. We estimate that variation in CAST and CAPN1 explains 1.02 and 1.85% of the phenotypic variation in WBSF respectively., (© 2012 The Authors, Animal Genetics © 2012 Stichting International Foundation for Animal Genetics.)

A whole-genome scan using single marker association was used to detect chromosome regions associated with seven female fertility traits in Finnish Ayrshire dairy cattle. The phenotypic data consisted of de-regressed estimated breeding values for 340 bulls which were estimated using a single trait model. Genotypes were obtained with the Illumina BovineSNP50 panel and a total of 35 630 informative, high-quality single nucleotide polymorphism (SNP) markers were used. The association analysis was performed using a mixed-model approach which fitted a fixed effect for each SNP and a random polygenic effect. We detected eleven genome-wide significant associations on eight different chromosomes. With at least chromosome-wise significance after Bonferroni correction, sixteen SNPs on nine chromosomes showed significant associations with one or more fertility traits. The results confirmed quantitative trait loci on three chromosomes (1, 2 and 20) for fertility traits previously reported for the same breed and one on chromosome four previously detected in Holstein cattle., (© 2011 The Authors, Animal Genetics © 2011 Stichting International Foundation for Animal Genetics.)

To gain insight into the number of loci of large effect that underlie variation in cattle, a quantitative trait locus (QTL) scan for 14 economically important traits was performed in two commercial Angus populations using 390 microsatellites, 11 single nucleotide polymorphisms (SNPs) and one duplication loci. The first population comprised 1769 registered Angus bulls born between 1955 and 2003, with Expected Progeny Differences computed by the American Angus Association. The second comprised 38 half-sib families containing 1622 steers with six post-natal growth and carcass phenotypes. Linkage analysis was performed by half-sib least squares regression with gridqtl or Bayesian Markov chain Monte Carlo analysis of complex pedigrees with loki. Of the 673 detected QTL, only 118 have previously been reported, reflecting both the conservative approach to QTL reporting in the literature, and the more liberal approach taken in this study. From 33 to 71% of the genetic variance and 35 to 56% of the phenotypic variance in each trait was explained by the detected QTL. To analyse the effects of 11 SNPs and one duplication locus within candidate genes on each trait, a single marker analysis was performed by fitting an additive allele substitution model in both mapping populations. There were 53 associations detected between the SNP/duplication loci and traits with -log(10) P(nominal) ≥ 4.0, where each association explained 0.92% to 4.4% of the genetic variance and 0.01% to 1.86% of the phenotypic variance. Of these associations, only six SNP/duplication loci were located within 8 cM of a QTL peak for the trait, with two being located at the QTL peak: SST&#95;DG156121:c.362A>G for ribeye muscle area and TG&#95;X05380:c.422C>T for calving ease. Strong associations between several SNP/duplication loci and trait variation were obtained in the absence of any detected linked QTL. However, we reject the causality of several commercialized DNA tests, including an association between TG&#95;X05380:c.422C>T and marbling in Angus cattle., (© 2010 The Authors, Animal Genetics © 2010 Stichting International Foundation for Animal Genetics.)