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Background/Objectives: The dairy industry relies on reproductive efficiency to maintain efficient milk production. Spontaneous abortion (SA), defined as pregnancy loss between gestation days 42 and 260, occurred in 4.5% of the artificially inseminated (AI) Holstein heifers and 31.6% of the embryo transfer (ET) recipient Holstein heifers that received in vitro-produced frozen embryos on a single dairy farm in Idaho. Methods: A genome-wide association analysis (GWAA) was performed to identify the associations (FDR p < 0.05) with SA in heifers that were bred by AI (1351 controls that delivered at term and 63 cases that aborted) that conceived following the first insemination, as well as in 59 controls and 273 cases of ET recipient heifers pregnant from the first ET. Results: There were 216 loci and 413 positional candidate genes associated (FDR p < 0.05) with SA in the heifers bred by AI in a recessive model and no loci associated with SA in the ET recipients. Conclusions: The identification of loci associated with SA in the heifers bred by AI may be used to reduce fetal loss through genomic selection.

Heifer conception rate to the first service (HCR1) is defined as the number of heifers that become pregnant to the first breeding service compared to the heifers bred. This study aimed to identify loci associated and gene sets enriched for HCR1 for heifers that were bred by artificial insemination (AI, n = 2829) or were embryo transfer (ET, n = 2086) recipients, by completing a genome-wide association analysis and gene set enrichment analysis using SNP data (GSEA-SNP). Three unique loci, containing four positional candidate genes, were associated ( p < 1 × 10 -5 ) with HCR1 for ET recipients, while the GSEA-SNP identified four gene sets (NES ≥ 3) and sixty-two leading edge genes (LEGs) enriched for HCR1. While no loci were associated with HCR1 bred by AI, one gene set and twelve LEGs were enriched (NES ≥ 3) for HCR1 with the GSEA-SNP. This included one gene ( PKD2 ) shared between HCR1 AI and ET services. Identifying loci associated or enriched for HCR1 provides an opportunity to use them as genomic selection tools to facilitate the selection of cattle with higher reproductive efficiency, and to better understand embryonic loss.

Pseudorabies virus (PRV)-the causative agent of Aujeszky's disease-was eliminated from commercial pig production herds in the United States (US) in 2004; however, PRV remains endemic among invasive feral swine ( Sus scrofa ). The circulation of PRV among abundant, widespread feral swine populations poses a sustained risk for disease spillover to production herds. Risk-based surveillance has been successfully implemented for PRV in feral swine populations in the US. However, understanding the role of host genetics in infection status may offer new insights into the epidemiology and disease dynamics of PRV that can be applied to management strategies. Genetic mechanisms underlying host susceptibility to PRV are relatively unknown; therefore, we sought to identify genomic regions associated with PRV infection status among naturally infected feral swine using genome-wide association studies (GWAS) and gene set enrichment analysis of single nucleotide polymorphism data (GSEA-SNP). Paired serological and genotypic data were collected from 6,081 feral swine distributed across the invaded range within the contiguous US. Three complementary study populations were developed for GWAS: 1) comprehensive population consisting of feral swine throughout the invaded range within the contiguous US; 2) population of feral swine under high, but temporally variable PRV infection pressure; and 3) population of feral swine under temporally stable, high PRV infection pressure. We identified one intronic SNP associated with PRV infection status within candidate gene AKAP6 on autosome 7. Various gene sets linked to metabolic pathways were enriched in the GSEA-SNP. Ultimately, improving disease surveillance efforts in feral swine will be critical to further understanding of the role host genetics play in PRV infection status, helping secure the health of commercial pork production., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Bowden, Kiser, Miller, Buckley, Boggiatto, Giglio, Brown, Garrick, Neibergs, Piaggio, Speidel and Smyser.)

Background: Delayed postoperative hemorrhage (DEPOH) is an important health concern for Scottish deerhounds., Hypothesis/objectives: Identify genes associated with DEPOH in Scottish deerhounds., Animals: Two hundred sixty-nine privately owned Scottish deerhounds., Methods: Retrospective case-control study. DEPOH cases and controls were identified through an owner health survey. Genome-wide association analysis was performed using whole genome sequences from 8 cases and 17 controls. All cases and controls were genotyped for selected variants., Results: Of 269 dogs, 10 met inclusion and exclusion criteria for DEPOH, while 62 controls had undergone similar surgical procedures without DEPOH. Genome-wide association analysis identified a single locus on chromosome 9 spanning 40 genes. One of these genes (SERPINF2 encoding alpha-2 antiplasmin) was directly linked to the pathophysiology of DEPOH. The entire cohort was genotyped for a missense SERPINF2 variant (c.605 C>T; p.A202V). Compared to dogs with the reference C/C genotype, the likelihood of DEPOH was significantly higher for dogs with the T/T genotype (odds ratio [OR] = 1235; 95% confidence interval [CI] = 23-6752; P = 0.0005) and with the C/T genotype (OR = 28; 95% CI = 1.4-542; P = 0.03)., Conclusions and Clinical Importance: SERPINF2 is associated with DEPOH in Scottish deerhounds. Genetic testing might be able to identify dogs that are susceptible to DEPOH., (© 2023 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Bovine coronavirus (BCoV) is associated with respiratory and enteric infections in both dairy and beef cattle worldwide. It is also one of a complex of pathogens associated with bovine respiratory disease (BRD), which affects millions of cattle annually. The objectives of this study were to identify loci and heritability estimates associated with BCoV infection and BRD in dairy calves and feedlot cattle. Dairy calves from California ( n = 1,938) and New Mexico ( n = 647) and feedlot cattle from Colorado ( n = 915) and Washington ( n = 934) were tested for the presence of BCoV when classified as BRD cases or controls following the McGuirk scoring system. Two comparisons associated with BCoV were investigated: (1) cattle positive for BCoV (BCoV + ) were compared to cattle negative for BCoV (BCoV - ) and (2) cattle positive for BCoV and affected with BRD (BCoV + BRD + ) were compared to cattle negative for BCoV and BRD (BCoV - BRD - ). The Illumina BovineHD BeadChip was used for genotyping, and genome-wide association analyses (GWAA) were performed using EMMAX (efficient mixed-model association eXpedited). The GWAA for BCoV + identified 51 loci ( p < 1 × 10 -5 ; 24 feedlot, 16 dairy, 11 combined) associated with infection with BCoV. Three loci were associated with BCoV + across populations. Heritability estimates for BCoV + were 0.01 for dairy, 0.11 for feedlot cattle, and 0.03 for the combined population. For BCoV + BRD + , 80 loci ( p < 1 × 10 -5 ; 26 feedlot, 25 dairy, 29 combined) were associated including 14 loci across populations. Heritability estimates for BCoV + BRD + were 0.003 for dairy, 0.44 for feedlot cattle, and 0.07 for the combined population. Several positional candidate genes associated with BCoV and BRD in this study have been associated with other coronaviruses and respiratory infections in humans and mice. These results suggest that selection may reduce susceptibility to BCoV infection and BRD in cattle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kiser and Neibergs.)

Bovine paratuberculosis, caused by Mycobacterium avium subspecies paratuberculosis ( MAP ), continues to impact the dairy industry through increased morbidity, mortality, and lost production. Although genome-wide association analyses (GWAAs) have identified loci associated with susceptibility to MAP , limited progress has been made in identifying mutations that cause disease susceptibility. A 235-kb region on Bos taurus chromosome 3 (BTA3), containing a 70-kb haplotype block surrounding endothelin 2 ( EDN2 ), has previously been associated with the risk of MAP infection. EDN2 is highly expressed in the gut and is involved in intracellular calcium signaling and a wide array of biological processes. The objective of this study was to identify putative causal mutations for disease susceptibility in the region surrounding EDN2 in Holstein and Jersey cattle. Using sequence data from 10 Holstein and 10 Jersey cattle, common variants within the 70-kb region containing EDN2 were identified. A custom SNP genotyping array fine-mapped the region using 221 Holstein and 51 Jersey cattle and identified 17 putative causal variants ( P < 0.01) located in the 5' region of EDN2 and a SNP in the 3' UTR ( P = 0.00009) associated with MAP infection. MicroRNA interference assays, mRNA stability assays, and electrophoretic mobility shift assays were performed to determine if allelic changes at each SNP resulted in differences in EDN2 stability or expression. Two SNPs [ rs109651404 (G/A) and rs110287192 (G/T)] located within the promoter region of EDN2 displayed differential binding affinity for transcription factors in binding sequences harboring the alternate SNP alleles. The luciferase reporter assay revealed that the transcriptional activity of the EDN2 promoter was increased ( P < 0.05) with the A allele for rs109651404 and the G allele for rs110287192 . These results suggest that the variants rs109651404 and rs110287192 are mutations that alter transcription and thus may alter susceptibility to MAP infection in Holstein and Jersey cattle., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Kiser, Wang, Zanella, Scraggs, Neupane, Cantrell, Van Tassell, White, Taylor and Neibergs.)

Bovine respiratory disease (BRD) is the costliest disease affecting the cattle industry globally. Orthomyxoviruses, influenza C virus (ICV) and influenza D virus (IDV) have recently been implicated to play a role in BRD. However, there are contradicting reports about the association of IDV and ICV to BRD. Using the largest cohort study (cattle, n = 599) to date we investigated the association of influenza viruses in cattle with BRD. Cattle were scored for respiratory symptoms and pooled nasal and pharyngeal swabs were tested for bovine viral diarrhea virus, bovine herpesvirus 1, bovine respiratory syncytial virus, bovine coronavirus, ICV and IDV by real-time PCR. Cattle that have higher viral loads of IDV and ICV also have greater numbers of co-infecting viruses than controls. More strikingly, 2 logs higher IDV viral RNA in BRD-symptomatic cattle that are co-infected animals than those infected with IDV alone. Our results strongly suggest that ICV and IDV may be significant contributors to BRD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Heifer conception rate (HCR) is defined as the percentage of inseminated heifers that become pregnant at each service. The genome-wide association analyses in this study focused on identifying the loci associated with Holstein heifer ( n = 2013) conception rate at first service (HCR1) and the number of times bred (TBRD) to achieve a pregnancy. There were 348 unique loci associated ( p < 5 × 10 -8 ) with HCR1 and 615 unique loci associated ( p < 5 × 10 -8 ) with TBRD. The two phenotypes shared 302 loci, and 56 loci were validated in independent cattle populations. There were 52 transcription factor binding sites (TFBS) and 552 positional candidate genes identified in the HCR1- and TBRD-associated loci. The positional candidate genes and the TFBS associated with HCR1 and TBRD were used in the ingenuity pathway analysis (IPA). In the IPA, 11 pathways, 207 master regulators and 11 upstream regulators were associated ( p < 1.23 × 10 -5 ) with HCR1 and TBRD. The validated loci associated with both HCR1 and TBRD make good candidates for genomic selection and further investigations to elucidate the mechanisms associated with subfertility and infertility.

The inability of beef cattle to maintain full term pregnancies has become an economic concern for the beef industry. Herd management and nutritional improvements have alleviated environmental impacts on embryonic and fetal loss, yet additional gains can be made through genomic selection. The objectives of this study were to identify loci and gene-sets in crossbred beef heifers associated with the number of services required to become pregnant (TBRD) and heifer conception rate at first service (HCR1). Heifers (n = 709) from a commercial beef operation underwent one round of artificial insemination, before exposure to bulls for natural service for 50 days. Pregnancy and time of conception was determined by ultrasound 35 days after the breeding season. Heifers were genotyped using the GeneSeek (Lincoln, NE) Bovine GGP50K BeadChip prior to genome-wide association analyses (GWAA) conducted using an EIGENSTRAT-like model to identify loci associated (P < 1 × 10-5) with TBRD and HCR1. One locus was associated (P = 8.97 × 10-6) with TBRD on BTA19 and included the positional candidate gene ASIC2, which is differentially expressed in the endometrium of fertility classified heifers, and the positional candidate gene, SPACA3. Gene-set enrichment analyses using SNP (GSEA-SNP) data, was performed and identified one gene-set, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen as enriched (NES = 3.15) with TBRD and contained nine leading edge genes that contributed to the enrichment of the gene set. The enriched gene-set is involved in catalyzing oxidation-reduction reactions, which have been associated with oxidative stressors impacting pregnancy success. No loci were associated nor gene-sets enriched with HCR1. Identification of loci, positional candidate genes, gene-sets and leading edge genes enriched for fertility facilitate genomic selection that allows producers to select for reproductively superior cattle, reduce costs associated with infertility, and increase percent calf crop., Competing Interests: The authors have declared that no competing interests exist.

Bovine respiratory disease (BRD) is considered one of the most economically important diseases in the cattle industry. Ultimately, the selection of cattle that are less susceptible to disease will allow producers to reduce the prevalence of BRD and lessen its economic impact. The objective of this study was to validate previously identified loci associated with susceptibility to BRD in an independent population of 140 pre-weaned Holstein calves from Wisconsin (WI). Using the McGuirk health scoring system, calves were classified as either clinically affected with BRD (n = 35) or healthy (n = 105). Additive genotypic tests were performed for genomic regions previously associated with susceptibility to BRD in calves from California (CA) and New Mexico (NM). Using this method, 4 loci (P < 0.01) consisting of 10 SNP were validated in the WI population, including 2 loci from CA, 1 locus from NM, and 1 locus from a combined CA + NM population. Most of the positional candidate genes and transcription factor binding site motifs associated with these loci have functions related to innate and adaptive immune responses. The validation of loci associated with susceptibility to BRD in independent populations allows producers to more reliably select cattle that are less susceptible to BRD, improving animal welfare, decreasing the annual revenue losses, and lowering the prevalence of the disease., (© 2019 Stichting International Foundation for Animal Genetics.)

Background: The objectives of this study were to identify loci, positional candidate genes, gene-sets, and pathways associated with spontaneous abortion (SA) in cattle and compare these results with previous human SA studies to determine if cattle are a good SA model for humans. Pregnancy was determined at gestation day 35 for Holstein heifers and cows. Genotypes from 43,984 SNPs of 499 pregnant heifers and 498 pregnant cows that calved at full term (FT) were compared to 62 heifers and 28 cows experiencing SA. A genome-wide association analysis, gene-set enrichment analysis-single nucleotide polymorphism, and ingenuity pathway analysis were used to identify regions, pathways, and master regulators associated with SA in heifers, cows, and a combined population., Results: Twenty-three loci and 21 positional candidate genes were associated ( p < 1 × 10 -5 ) with SA and one of these (KIR3DS1) has been associated with SA in humans. Eight gene-sets (NES > 3.0) were enriched in SA and one was previously reported as enriched in human SA. Four master regulators ( p < 0.01) were associated with SA within two populations., Conclusions: One locus associated with SA was validated and 39 positional candidate and leading-edge genes and 2 gene-sets were enriched in SA in cattle and in humans.

Background: Subfertility is a major issue facing the dairy industry as the average US Holstein cow conception rate (CCR) is approximately 35%. The genetics underlying the physiological processes responsible for CCR, the proportion of cows able to conceive and maintain a pregnancy at each breeding, are not well characterized. The objectives of this study were to identify loci, positional candidate genes, and transcription factor binding sites (TFBS) associated with CCR and determine if there was a genetic correlation between CCR and milk production in primiparous Holstein cows. Cows were bred via artificial insemination (AI) at either observed estrus or timed AI and pregnancy status was determined at day 35 post-insemination. Additive, dominant, and recessive efficient mixed model association expedited (EMMAX) models were used in two genome-wide association analyses (GWAA). One GWAA focused on CCR at first service (CCR1) comparing cows that conceived and maintained pregnancy to day 35 after the first AI (n = 494) to those that were open after the first AI (n = 538). The second GWAA investigated loci associated with the number of times bred (TBRD) required for conception in cows that either conceived after the first AI (n = 494) or repeated services (n = 472)., Results: The CCR1 GWAA identified 123, 198, and 76 loci associated (P < 5 × 10 - 08 ) in additive, dominant, and recessive models, respectively. The TBRD GWAA identified 66, 95, and 33 loci associated (P < 5 × 10 - 08 ) in additive, dominant, and recessive models, respectively. Four of the top five loci were shared in CCR1 and TBRD for each GWAA model. Many of the associated loci harbored positional candidate genes and TFBS with putative functional relevance to fertility. Thirty-six of the loci were validated in previous GWAA studies across multiple breeds. None of the CCR1 or TBRD associated loci were associated with milk production, nor was their significance with phenotypic and genetic correlations to 305-day milk production., Conclusions: The identification and validation of loci, positional candidate genes, and TFBS associated with CCR1 and TBRD can be utilized to improve, and further characterize the processes involved in cattle fertility.

Background: Subfertility is one challenge facing the dairy industry as the average Holstein heifer conception rate (HCR), the proportion of heifers that conceive and maintain a pregnancy per breeding, is estimated at 55-60%. Of the loci associated with HCR, few have been validated in an independent cattle population, limiting their usefulness for selection or furthering our understanding of the mechanisms involved in successful pregnancy. Therefore, the objectives here were to identify loci associated with HCR: 1) to the first artificial insemination (AI) service (HCR1), 2) to repeated AI services required for a heifer to conceive (TBRD) and 3) to validate loci previously associated with fertility. Breeding and health records from 3359 Holstein heifers were obtained after heifers were bred by AI at observed estrus, with pregnancy determined at day 35 via palpation. Heifer DNA was genotyped using the Illumina BovineHD BeadChip, and genome-wide association analyses (GWAA) were performed with additive, dominant and recessive models using the Efficient Mixed Model Association eXpedited (EMMAX) method with a relationship matrix for two phenotypes. The HCR1 GWAA compared heifers that were pregnant after the first AI service (n = 497) to heifers that were open following the first AI service (n = 405), which included those that never conceived. The TBRD GWAA compared only those heifers which did conceive, across variable numbers of AI service (n = 712). Comparison of loci previously associated with fertility, HCR1 or TBRD were considered the same locus for validation when in linkage disequilibrium (D' > 0.7)., Results: The HCR1 GWAA identified 116, 187 and 28 loci associated (P < 5 × 10 - 8 ) in additive, dominant and recessive models, respectively. The TBRD GWAA identified 235, 362, and 69 QTL associated (P < 5 × 10 - 8 ) with additive, dominant and recessive models, respectively. Loci previously associated with fertility were in linkage disequilibrium with 22 loci shared with HCR1 and TBRD, 5 HCR1 and 19 TBRD loci., Conclusions: Loci associated with HCR1 and TBRD that have been identified and validated can be used to improve HCR through genomic selection, and to better understand possible mechanisms associated with subfertility.

Milk production traits, such as 305-day milk yield (305MY), have been under direct selection to improve production in dairy cows. Over the past 50 years, the average milk yield has nearly doubled, and over 56% of the increase is attributable to genetic improvement. As such, additional improvements in milk yield are still possible as new loci are identified. The objectives of this study were to detect SNPs and gene sets associated with 305MY in order to identify new candidate genes contributing to variation in milk production. A population of 781 primiparous Holstein cows from six central Washington dairies with records of 305MY and energy corrected milk were used to perform a genome-wide association analysis (GWAA) using the Illumina BovineHD BeadChip (777 962 SNPs) to identify QTL associated with 305MY (P < 1.0 × 10 -5 ). A gene set enrichment analysis with SNP data (GSEA-SNP) was performed to identify gene sets (normalized enrichment score > 3.0) and leading edge genes (LEGs) influencing 305MY. The GWAA identified three QTL comprising 34 SNPs and 30 positional candidate genes. In the GSEA-SNP, five gene sets with 58 unique and 24 shared LEGs contributed to 305MY. Identification of QTL and LEGs associated with 305MY can provide additional targets for genomic selection to continue to improve 305MY in dairy cattle., (© 2019 Stichting International Foundation for Animal Genetics.)

Consumption of an adequate volume of high-quality colostrum soon after birth is critical for a calf's health. Few studies have focused on the genetics associated with colostrum production, even though several dairy herds in the United States have reported incidents of low to no colostrum production during the fall and winter seasons. The objectives of this study were to identify loci associated with quantity and quality of colostrum production in a herd of Jersey cattle (n = 345) and to identify potential positional candidate genes and/or transcription factor binding site motifs located near associated loci. Cattle that freshened between the months of October and December of 2016 at a single dairy were enrolled in the study and produced on average 3.03 kg of colostrum at their first milking. This study included 112 cattle genotyped with the GeneSeek GGP50k BeadChip and another 233 cattle previously genotyped with various other arrays. The 233 cattle genotyped at lower densities were imputed to the GGP50k BeadChip density using BEAGLE 4.1.1, and 2 genome-wide association analyses (GWAA) were conducted using an additive efficient mixed-model association expedited method with a genomic relationship matrix (EMMAX-GRM). The first GWAA investigated loci associated with colostrum quantity and identified 7 loci: 6 that were moderately associated (5 × 10-07 > P < 1 × 10-05) and 1 that was strongly associated (P < 5 × 10-07). The second GWAA investigated colostrum quality and identified 1 moderately (5 × 10-07 > P < 1 × 10-05) associated locus. Five loci harbored positional candidate genes which had functional relevance to colostrum production, and 1 locus located on BTA10 contained a transcription factor binding site motif for TFAP2A which has previously been linked to mammary gland development. Pseudoheritability estimates were moderate for colostrum quality (0.19 ± 0.06) and high for colostrum quantity (0.76 ± 0.11), suggesting that genomic selection for these traits would be possible. Diminished colostrum quantity or quality can have a significant impact on herd health and herd economics. The identification of loci, positional candidate genes, and transcription factor binding site motifs associated with colostrum production could be used in genomic selection to allow producers to select for cattle with good colostrum production, improving calf health, and reducing economic losses to the herd., (© The Author(s) 2018. Published by Oxford University Press on behalf of the American Society of Animal Science. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Bovine respiratory disease (BRD) is a complex disease that is associated with infection by bacterial and viral pathogens when cattle fail to adequately respond to stress. The objective of this study was to use gene set enrichment analysis of SNP data (GSEA-SNP) and a network analysis (ingenuity pathway analysis) to identify gene sets, genes within gene sets (leading-edge genes) and upstream regulators associated with BRD in pre-weaned dairy calves and beef feedlot cattle. BRD cases and controls were diagnosed using the McGuirk health scoring system. Holstein calves were sampled from commercial calf-raising facilities in California (1003 cases and 1011 controls) and New Mexico (376 cases and 372 controls). Commercial feedlot cattle were sampled from Colorado (500 cases and 499 controls) and Washington (504 cases and 497 controls). There were 102 and 237 unique leading-edge genes identified in the dairy calf and beef cattle populations respectively. Six leading-edge genes (ADIPOQ, HTR2A, MIF, PDE6G, PRDX3 and SNCA) were associated with BRD in both dairy and beef cattle. Network analysis identified glucose as the most influential upstream regulator in dairy cattle, whereas in beef cattle, TNF was the most influential upstream regulator. The genes, gene sets and upstream regulators associated with BRD have common functions associated with immunity, inflammation and pulmonary disease and provide insights into the mechanisms that are critical to BRD susceptibility in cattle., (© 2018 Stichting International Foundation for Animal Genetics.)

Multiple genome-wide association analyses have investigated susceptibility to bovine paratuberculosis, but few loci have been identified across independent cattle populations. A SNP-based gene set enrichment analysis (GSEA-SNP) allows expanded identification of genes with moderate effects on a trait through the enrichment of gene sets instead of identifying only few loci with large effects. Therefore, the objective of this study was to identify genes that were moderately associated with Mycobacterium avium ssp. paratuberculosis (Map) tissue infection using GSEA-SNP in Holstein cattle from the Pacific Northwest (PNW; n = 205) and from the PNW and Northeast (PNW+NE; n = 245) which were previously genotyped with the Illumina BovineSNP50 BeadChip. The GSEA-SNP utilized 4389 gene sets from five databases. For each annotated gene in the UMD3.1 assembly (n = 19,723), the most significant SNP within each gene and its surrounding region (10 kb up- and downstream) was selected as a proxy for that gene. Any gene set with a normalized enrichment score > 2.5 was considered enriched. Thirteen gene sets (8 PNW GSEA-SNP; 5 PNW+NE) were enriched in these analyses and all have functions that relate to nuclear factor kappa beta. Nuclear factor kappa beta is critical to gut immune responses, implicated in host immune responses to other mycobacterial diseases, and has established roles in inflammation as well as cancer. Gene sets and genes moderately associated with Map infection could be used in genomic selection to allow producers to select for less susceptible cattle, lower the prevalence of the disease, and reduce economic losses.

Consumption of an adequate volume of high-quality colostrum is vital to a dairy calf's ability to survive and become a productive herd member. However, some dairy herds have reported a deficiency of colostrum production, which ranges from a low volume to no colostrum produced, by cows during fall and winter. Little information regarding this phenomenon exists. The purpose of this study was to characterize the syndrome and identify potential risk factors for low colostrum yield. A 2,500-cow Jersey dairy farm was enrolled in a prospective cohort study in May 2016, to evaluate possible effects of photoperiod, temperature, and cow factors on colostrum production. Dairy personnel were trained to collect, weigh, and evaluate colostrum quality. Information on parity, previous lactation length, previous 305-d mature-equivalent milk production, and dry period length were collected through the farm's dairy management software. Weather and photoperiod data were also collected. Over the year of enrollment, 2,988 eligible cows calved and had colostrum weights recorded and 38% were primiparous (n = 1,143), 25% were in their second lactation (n = 752), and 37% were in their third or greater lactation (n = 1,093). The overall average colostrum yield was 6.6 kg/cow in June 2016, 2.5 kg/cow in December 2016, and 4.8 kg/cow in May 2017. Multiparous cows had a larger decline in colostrum production between June and December (6.6 to 1.3 kg/cow) compared with primiparous animals (6.5 to 4.2 kg/cow). Overall, average colostrum production decreased by 0.17 kg/cow per week during this time, 0.22 kg for multiparous cows and 0.08 kg for primiparous cows. A logistic regression model was constructed for all cows to evaluate effects of cow factors on low colostrum production (<2.7 kg at first milking). Dry period length, calf sex, singleton or twin, age at freshening, month of calving and previous lactation length were significantly associated with the probability of low colostrum yield (<2.7 kg at first milking). A cross-correlation function analysis between the time series for colostrum yield and photoperiod revealed a high correlation at the time of calving and 1 mo prior, particularly for multiparous cows. A pedigree analysis showed that extreme colostrum yield (low vs. high) followed some sire lines. Low colostrum production in this herd could have an economic effect on the dairy and calf health and appears to have a strong seasonal and, potentially, a genetic component., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

Infertility and subfertility negatively impact the economics and reproductive performance of cattle. Of note, significant pregnancy loss occurs in cattle during the first month of pregnancy, yet little is known about the genetic loci influencing pregnancy success and loss in cattle. To identify quantitative trait loci (QTL) with large effects associated with early pregnancy loss, Angus crossbred heifers were classified based on day 28 pregnancy outcomes to serial embryo transfer. A genome wide association analysis (GWAA) was conducted comparing 30 high fertility heifers with 100% success in establishing pregnancy to 55 subfertile heifers with 25% or less success. A gene set enrichment analysis SNP (GSEA-SNP) was performed to identify gene sets and leading edge genes influencing pregnancy loss. The GWAA identified 22 QTL (p < 1 x 10-5), and GSEA-SNP identified 9 gene sets (normalized enrichment score > 3.0) with 253 leading edge genes. Network analysis identified TNF (tumor necrosis factor), estrogen, and TP53 (tumor protein 53) as the top of 671 upstream regulators (p < 0.001), whereas the SOX2 (SRY [sex determining region Y]-box 2) and OCT4 (octamer-binding transcription factor 4) complex was the top master regulator out of 773 master regulators associated with fertility (p < 0.001). Identification of QTL and genes in pathways that improve early pregnancy success provides critical information for genomic selection to increase fertility in cattle. The identified genes and regulators also provide insight into the complex biological mechanisms underlying pregnancy establishment in cattle.

Bovine respiratory disease (BRD) is an economically important disease of feedlot cattle that is caused by viral and bacterial pathogen members of the BRD complex. Many cases of subclinical BRD go untreated and are not detected until slaughter, when lung lesions are identified. The objectives of this study were to identify which BRD pathogens were associated with the presence of lung lesions at harvest and to identify genomic loci that were associated with susceptibility to lung lesions as defined by consolidation of the lung and/or the presence of fibrin tissue. Steers from a Colorado feedlot ( = 920) were tested for the presence of viral and bacterial pathogens using deep pharyngeal and mid-nasal swabs collected on entry into the study. Pathogen profiles were compared between cattle with or without lung consolidation (LC), fibrin tissue in the lung (FT), a combination of LC and FT in the same lung (lung lesions [LL]), and hyperinflated lungs (HIF) at harvest. Genotyping was conducted using the Illumina BovineHD BeadChip. Genomewide association analyses (GWAA) were conducted using EMMAX (efficient mixed-model association eXpedited), and pseudoheritabilities were estimated. The pathogen profile comparisons revealed that LC ( = 0.01, odds ratio [OR] = 3.37) and LL cattle ( = 0.04, OR = 4.58) were more likely to be infected with bovine herpes virus-1 and that HIF cattle were more likely to be infected with spp. ( = 0.04, OR = 4.33). Pseudoheritability estimates were 0.25 for LC, 0.00 for FT, 0.28 for LL, and 0.13 for HIF. Because pseudoheritability for FT was estimated to be 0, GWAA results for FT were not reported. There were 4 QTL that were moderately associated ( < 1 × 10) with only LC, 2 that were associated with only LL, and 1 that was associated with LC and LL. Loci associated with HIF included 12 that were moderately associated and 3 that were strongly associated (uncorrected P < 5 × 10-7). A 24-kb region surrounding significant lead SNP was investigated to identify positional candidate genes. Many positional candidate genes underlying or flanking the detected QTL have been associated with signal transduction, cell adhesion, or gap junctions, which have functional relevance to the maintenance of lung health. The identification of pathogens and QTL associated with the presence of lung abnormalities in cattle exhibiting subclinical BRD allows the identification of loci that may not be detected through manifestation of clinical disease alone.

Johne's disease is a contagious bacterial infection of cattle caused by ssp. (). A previous genome-wide association analysis (GWAA) in Holstein cattle identified QTL on BTA3 and BTA9 that were highly associated (P < 5 × 10) and on BTA1, BTA16, and BTA21 that were moderately associated (P < 5 × 10) with Map tissue infection. The objectives of this study were to validate previous GWAA results in Jersey cattle ( = 57), Holstein cattle from the Pacific Northwest (PNW, = 205) and a combined Holstein population from the PNW and the Northeast (PNW + NE, = 423), and also identify new loci associated with tissue infection. DNA was genotyped using the Illumina BovineSNP50 BeadChip, and the PNW + NE data was also imputed to whole genome sequence level using Run4 of the 1000 Bull Genomes project with Beagle v 4.1 and FImpute. Cases were ileocecal node positive and controls were negative for by quantitative PCR (qPCR). Individuals were removed for SNP call rate < 90%, and SNP were removed for genotype call rate < 90% or minor allele frequency < 1%. For the Jersey, PNW, and PNW + NE, GWAA were conducted using an allelic dosage model. For the PNW and the PNW + NE, an additional efficient mixed-model association eXpedited (EMMAX) analysis was performed using additive, dominance and recessive models. Seven QTL on BTA22 were identified in the Jersey population with the most significant ( = 4.45 × 10) located at 21.7 megabases (Mb). Six QTL were associated in the PNW and the PNW + NE analyses, including a QTL previously identified on BTA16 in the NE population. The most significant locus for the PNW was located on BTA21 at 61 Mb ( = 8.61 × 10) while the most significant locus for the PNW + NE was on BTA12 at 90 Mb ( = 2.33 × 10). No additional QTL were identified with the imputed GWAA. Putative positional candidate genes were identified within 50 kb 5' and 3' of each QTL. Two positional candidate genes were identified in Jersey cattle, 1 identified in the PNW and 8 in the PNW + NE populations. Many identified positional candidate genes are involved in signal transduction, have immunological functions, or have putative functional relevance in entry into host cells. This study supported 2 previously identified SNP within a QTL on BTA16 and identified 16 new QTL, including 2 found in the PNW and the PNW+NE, associated with tissue infection.

Background: Bovine respiratory disease complex (BRDC) is an infectious disease of cattle that is caused by a combination of viral and/or bacterial pathogens. Selection for cattle with reduced susceptibility to respiratory disease would provide a permanent tool for reducing the prevalence of BRDC. The objective of this study was to identify BRDC susceptibility loci in pre-weaned Holstein calves as a prerequisite to using genetic improvement as a tool for decreasing the prevalence of BRDC. High density SNP genotyping with the Illumina BovineHD BeadChip was conducted on 1257 male and 757 female Holstein calves from California (CA), and 767 calves identified as female from New Mexico (NM). Of these, 1382 were classified as BRDC cases, and 1396 were classified as controls, with all phenotypes assigned using the McGuirk health scoring system. During the acquisition of blood for DNA isolation, two deep pharyngeal and one mid-nasal diagnostic swab were obtained from each calf for the identification of bacterial and viral pathogens. Genome-wide association analyses were conducted using four analytical approaches (EIGENSTRAT, EMMAX-GRM, GBLUP and FvR). The most strongly associated SNPs from each individual analysis were ranked and evaluated for concordance. The heritability of susceptibility to BRDC in pre-weaned Holstein calves was estimated., Results: The four statistical approaches produced highly concordant results for 373 top ranked SNPs that defined 126 chromosomal regions for the CA population. Similarly, in NM, 370 SNPs defined 138 genomic regions that were identified by all four approaches. When the two populations were combined (i.e., CA + NM) and analyzed, 324 SNPs defined 116 genomic regions that were associated with BRDC across all analytical methods. Heritability estimates for BRDC were 21% for both CA and NM as individual populations, but declined to 13% when the populations were combined., Conclusions: Four analytical approaches utilizing both single and multi-marker association methods revealed common genomic regions associated with BRDC susceptibility that can be further characterized and used for genomic selection. Moderate heritability estimates were observed for BRDC susceptibility in pre-weaned Holstein calves, thereby supporting the application of genomic selection to reduce the prevalence of BRDC in U.S. Holsteins.