Contents of milk fatty acids (FA) display remarkable alterations along climatic gradients. Detecting candidate genes underlying such alterations might be beneficial for the exploration of climate sensitivity in dairy cattle. Consequently, we aimed on the definition of FA heat stress indicators, considering FA breeding values in response to temperature-humidity index (THI) alterations. Indicators were used in GWAS, in ongoing gene annotations and for the estimation of chromosome-wide variance components. The phenotypic data set consisted of 39,600 test-day milk FA records from 5,757 first-lactation Holstein dairy cows kept in 16 large-scale German cooperator herds. The FA traits were C18:0, polyunsaturated fatty acids (PUFA), saturated fatty acids (SFA), and unsaturated fatty acids (UFA). After genotype quality control, 40,523 SNP markers from 3,266 cows and 930 sires were considered. Meteorological data from the weather station in closest herd distance were used for the calculation of maximum hourly daily THI, which were allocated to 10 different THI classes. The same FA from 3 stages of lactation were considered as different, but genetically correlated traits. Consequently, a 3-trait reaction norm model was used to estimate genetic parameters and breeding values for FA along THI classes, considering either pedigree (A) or genomic (G) relationship matrices. De-regressed proofs and genomic estimated breeding values at the intermediate THI class 5 and at the extreme THI class 10 were used as pseudophenotypes in ongoing genomic analyses for thermoneutral (TNC) and heat stress conditions (HSC), respectively. The differences in de-regressed proofs and in genomic estimated breeding values from both THI classes were pseudophenotypes for heat stress response (HSR). Genetic correlations between the same FA under TNC and HSC were smallest in the first lactation stage and ranged from 0.20 for PUFA to 0.87 for SFA when modeling with the A matrix, and from 0.35 for UFA to 0.86 for SFA when modeling with the G matrix. In the first lactation stage, larger additive genetic variances under HSC compared with TNC indicate climate sensitivity for C18:0, PUFA, and UFA. Climate sensitivity was also reflected by pronounced chromosome-wide genetic variances for HSR of PUFA and UFA in the first stage of lactation. For all FA under TNC, HSC, and HSR, quite large genetic variance proportions were explained by BTA14. In GWAS, 30 SNP (within or close to 38 potential candidate genes) overlapped for HSR of the different FA. One unique potential candidate gene (AMFR) was detected for HSR of PUFA, 15 for HSR of SFA (ADGRB1, DENND3, DUSP16, EFR3A, EMP1, ENSBTAG00000003838, EPS8, MGP, PIK3C2G, STYK1, TMEM71, GSG1, SMARCE1, CCDC57, and FASN) and 3 for HSR of UFA (ENSBTAG00000048091, PAEP, and EPPK1). The identified unique genes play key roles in milk FA synthesis and are associated with disease resistance in dairy cattle. The results suggest consideration of FA in combination with climatic responses when inferring genetic mechanisms of heat stress in dairy cows.

The aim of this study was to estimate genotype by time-lagged heat stress (HS) variance components as well as main and interaction SNP-marker effects for maternal HS during the last eight weeks of cow pregnancy, considering milk production traits recorded in the offspring generation. The HS indicator was the temperature humidity index (THI) for each week. A dummy variable with the code = 1 for the respective week for THI ≥ 60 indicated HS, otherwise, for no HS, the code = 0 was assigned. The dataset included test-day and lactation production traits from 14,188 genotyped first parity Holstein cows. After genotype quality control, 41,139 SNP markers remained for the genomic analyses. Genomic animal models without (model VC_nHS) and with in-utero HS effects (model VC_wHS) were applied to estimate variance components. Accordingly, for genome-wide associations, models GWA_nHS and GWA_wHS, respectively, were applied to estimate main and interaction SNP effects. Common genomic and residual variances for the same traits were very similar from models VC_nHS and VC_wHS. Genotype by HS interaction variances varied, depending on the week with in-utero HS. Among all traits, lactation milk yield with HS from week 5 displayed the largest proportion for interaction variances (0.07). For main effects from model GWA_wHS, 380 SNPs were suggestively associated with all production traits. For the SNP interaction effects from model GWA_wHS, we identified 31 suggestive SNPs, which were located in close distance to 62 potential candidate genes. The inferred candidate genes have various biological functions, including mechanisms of immune response, growth processes and disease resistance. Two biological processes excessively represented in the overrepresentation tests addressed lymphocyte and monocyte chemotaxis, ultimately affecting immune response. The modelling approach considering time-lagged genotype by HS interactions for production traits inferred physiological mechanisms being associated with health and immunity, enabling improvements in selection of robust animals.

The aim of this study was to infer the effects of heat stress (HS) of dams during late gestation on direct and maternal genetic parameters for pneumonia (PNEU, 112,563 observations), diarrhea (DIAR, 176,904 observations), and omphalitis (OMPH, 176,872 observations) in Holstein calves kept in large-scale co-operator herds. The genotype dataset included 41,135 SNPs from 19,247 male and female cattle. Temperature-humidity indices (THI) during the last 8 wk of pregnancy were calculated, using the climate data from the nearest public weather station for each herd. Heat load effects were considered for average weekly THI larger than 60. Phenotypically, regression coefficients of calf diseases on prenatal THI during the last 8 wk of gestation were estimated in 8 consecutive runs. The strongest detrimental effects of prenatal HS on PNEU and DIAR were identified for the last week of pregnancy (wk 1). Thus, only wk 1 was considered in ongoing genetic and genomic analyses. In an advanced model considering prenatal HS, random regression coefficients on THI in wk 1 nested within maternal genetic effects (maternal slope effects for heat load) were considered as parameters to infer maternal sensitivity in response to prenatal THI alterations. Direct heritabilities from the advanced model ranged from 0.10 (THI 60) to 0.08 (THI 74) for PNEU and were close to 0.16 for DIAR. Maternal heritabilities for PNEU increased from 0.03 to 0.10 along the THI gradient. For DIAR, the maternal heritability was largest (0.07) at the minimum THI (THI = 60) and decreased to 0.05 at THI 74. Genetic correlations smaller than 0.80 for PNEU and DIAR recorded at THI 60 with corresponding diseases at THI 74 indicated genotype by climate interactions for maternal genetic effects. Genome-wide associations studies were performed using de-regressed proofs of genotyped sires for direct genetic, maternal genetic, and maternal slope effects. Thirty suggestive and 2 significant SNPs were identified from the GWAS. Forty-three genes located close to the suggestive SNPs (±100 kb) were annotated as potential candidate genes. Three biological processes were inferred on the basis of the these genes, addressing the negative regulation of the viral life cycle, innate immune response, and protein ubiquitination. Hence, the genetics of prenatal heat stress mechanisms are associated with immune physiology and disease resistance mechanisms.

With regard to potential applications of genomic selection in small numbered breeds, we evaluated genomic models and focused on potential candidate gene annotations for weight and meat quality traits in the local Rotes Höhenvieh (RHV) breed. Traits included 6,003 birth weights (BWT), 5,719 200 d-weights (200dw), 4,594 365 d-weights (365dw), and 547 records for intramuscular fat content (IMF). A total of 581,304 SNP from 370 genotyped cattle with phenotypic records were included in genomic analyses. Model evaluations focused on single- and multiple-trait models with direct and with direct and maternal genetic effects. Genetic relationship matrices were based on pedigree (A-matrix), SNP markers (G-matrix), or both (H-matrix). Genome-wide association studies (GWASs) were carried out using linear mixed models to identify potential candidate genes for the traits of interest. De-regressed proofs (DRP) for direct and maternal genetic components were used as pseudo-phenotypes in the GWAS. Accuracies of direct breeding values were higher from models based on G or on H compared to A. Highest accuracies (> 0.89) were obtained for IMF with multiple-trait models using the G-matrix. Direct heritabilities with maternal genetic effects ranged from 0.62 to 0.66 for BWT, from 0.45 to 0.55 for 200dW, from 0.40 to 0.44 for 365dW, and from 0.48 to 0.75 for IMF. Maternal heritabilities for BWT, 200dW, and 365dW were in a narrow range from 0.21 to 0.24, 0.24 to 0.27, and 0.21 to 0.25, respectively, and from 0.25 to 0.65 for IMF. Direct genetic correlations among body weight traits were positive and favorable, and very similar from different models but showed a stronger variation with 0.31 (A), −0.13 (G), and 0.45 (H) between BWT and IMF. In gene annotations, we identified 6, 3, 1, and 6 potential candidate genes for direct genetic effect on BWT, 200dW, 365dW, and IMF traits, respectively. Regarding maternal genetic effects, four (SHROOM3, ZNF609, PECAM1, and TEX2) and two (TMEM182 and SEC11A) genes were detected as potential candidate genes for BWT and 365dW, respectively. Potential candidate genes for maternal effect on IMF were GRHL2, FGA, FGB, and CTNNA3. As the most important finding from a practical breeding perspective, a small number of genotyped RHV cattle enabled accurate breeding values for high heritability IMF.

Climate change causes rising temperatures and extreme weather events worldwide, with possible detrimental time-lagged and acute impact on production and functional traits of cattle kept in outdoor production systems. The aim of the present study was to infer the influence of mean daily temperature humidity index (mTHI) and number of heat stress days (nHS) from different recording periods on birth weight (BWT), 200 d- and 365 d-weight gain (200 dg, 365 dg) of calves, and on the probability of stillbirth (SB), and calving interval (CINT) of their dams. Data recording included 4,362 observations for BWT, 3,136 observations for 200 dg, 2,502 observations for 365 dg, 9,293 observations for the birth status, and 2,811 observations for CINT of the local dual-purpose cattle breed “Rotes Höhenvieh” (RHV). Trait responses on mTHI and nHS were studied via generalized linear mixed model applications with identity link functions for Gaussian traits (BWT, 200 dg, 365 dg, CINT) and logit link functions for binary SB. High mTHI and high nHS before autumn births had strongest detrimental impact on BWT across all antepartum- (a.p.) periods (34.4 ± 0.79 kg maximum). Prolonged CINT was observed when cows suffered heat stress (HS) before or after spring calvings, with maximum length of 391.6 ± 3.82 d (56 d a.p.-period). High mTHI and high nHS during the 42 d- and 56 d a.p.-period implied increased probabilities for SB. We found a significant (P < 0.05) seasonal effect on SB in model 3 across all a.p.-periods, with the highest probability in autumn (maximum of 5.4 ± 0.82% in the 7 d a.p.-period). Weight gains of calves (200 dg and 365 dg) showed strongest HS response for mTHI and nHS measurements from the long-term postnatal periods (42 d- and 56 d-periods), with minimum 200 dg of 194.2 ± 4.15 kg (nHS of 31 to 42 d in the 42 d-period) or minimum 365 dg of 323.8 ± 3.82 kg (mTHI ≥ 60 in the 42 d-period). Calves born in summer, combined with high mTHI or high nHS pre- or postnatal, had lower weight gains, compared with calves born in other calving seasons or under cooler conditions. Highest BWT, weight gains, and shortest CINT mostly were detected under cool to moderate climate conditions for mTHI, and small to moderate nHS. Results indicate acute and time-lagged HS effects and address possible HS-induced epigenetic modifications of the bovine genome across generations and limited acclimatization processes to heat, especially when heat occurs during the cooler spring and autumn months.

Impact of direct heat stress (HS) on genetic parameter estimates, i.e., HS close to the trait recording date, was verified in several previous studies conducted in dairy and beef cattle populations. The aim of the present study was to analyze the impact of time-lagged HS at different recording periods during late pregnancy (a.p.) and postpartum (p.p.) on genetic parameter estimates for birth weight (BWT) and weight gain traits (200 d- and 365 d-weight gain (200dg, 365dg)) in offspring of the dual-purpose cattle breed “Rotes Höhenvieh” (RHV). Furthermore, we estimated genetic correlations within traits across time-lagged climatic indicators, in order to proof possible genotype by environment interactions (G×E). Trait recording included 5,434 observations for BWT, 3,679 observations for 200dg and 2,998 observations for 365dg. Time-lagged climatic descriptors were classes for the mean temperature humidity index (mTHI) and number of HS days (nHS) from the following periods: 7 d-period a.p. (BWT), 56 d-period a.p., and 56 d-period p.p. (200dg and 365dg). Genetic parameters were estimated via 2-trait animal models, i.e., defining the same trait in different climatic environments as different traits. Genetic variances and heritabilities for all traits increased with increasing mTHI- and nHS-classes for all recording periods, indicating pronounced genetic differentiation with regard to time-lagged in utero HS and HS directly after birth. Similarly, in low mTHI- and nHS-classes indicating cold stress, genetic variances, and heritabilities were larger than for temperate climates. Genetic correlations substantially smaller than 0.80 indicating G × E were observed when considering same traits from mTHI- and nHS-classes in greater distance. Estimated breeding values (EBV) of the 10 most influential sires with the largest number of offspring records fluctuated across mTHI- and nHS-classes. Correlations between sire EBV for same traits from distant climatic classes confirmed the genetic correlation estimates. Sires displaying stable EBV with climatic alterations were also identified. Selection of those sires might contribute to improved robustness in the RHV outdoor population genetically.