Interactions of human chorionic gonadotropin with genotype and parity on fertility responses of lactating dairy cows

Fertility-promoting effects of treatment of lactating dairy cattle with human chorionic gonadotropin (hCG) after artificial insemination (AI) have been variable. Here, we tested whether fertility response to hCG in lactating Holstein cows interacts with genotype and parity. Primiparous (n = 538) and multiparous (n = 613) cows were treated with hCG (3,300 IU) or vehicle 5 d after AI. Pregnancy was diagnosed on d 32 and 60 after AI. A subset of cows (n = 593–701) was genotyped for 4 single nucleotide polymorphisms (SNP) previously associated with fertility. Treatment with hCG increased progesterone concentration on d 12 after AI regardless of genotype or parity. Pregnancy per AI was improved by hCG in primiparous cows but not in multiparous cows. Moreover, hCG treatment interacted with a SNP in coenzyme Q9 (COQ9) to affect fertility. Fertility of cows treated with vehicle was greatest for the AA allele, whereas fertility was lowest for the same genotype among cows treated with hCG. Pregnancy per AI was also affected by genotype for heat shock protein A1-like (HSPA1L) and progesterone receptor (PGR), but no interactions were observed with treatment. Genotype for a SNP in prostate androgen-regulated mucin-like protein 1 (PARM1) was not associated with fertility. Overall, results show that variation in response to hCG treatment on fertility depends on parity and interacts with a SNP in COQ9.     

Candidate genes associated with the heritable humoral response to Mycobacterium avium ssp. paratuberculosis in dairy cows have factors in common with gastrointestinal diseases in humans

Infection of cattle with bovine paratuberculosis (i.e., Johne's disease) is caused by Mycobacterium avium ssp. paratuberculosis (MAP) and results in a chronic incurable gastroenteritis. This disease, which has economic ramifications for the cattle industry, is increasing in detected prevalence globally; subclinically infected animals can silently shed the bacterium into the environment for years, exposing contemporaries and hampering disease-control programs. The objective of the present study was to first quantify the genetic parameters for humoral response to MAP in dairy cattle. This was followed by a genome-based association analysis and subsequent downstream bioinformatic analyses from imputed whole genome sequence SNP data. After edits, ELISA test records were available on 136,767 cows; analyses were also undertaken on a subset of 33,818 of these animals from herds with at least 5 MAP ELISA-positive cows, with at least 1 of those positive cows being homebred. Variance components were estimated using univariate animal and sire linear mixed models. The heritability calculated from the animal model for humoral response to MAP using alternative phenotype definitions varied from 0.02 (standard error = 0.003) to 0.05 (standard error = 0.008). The genome-based associations were undertaken within a mixed model framework using weighted deregressed estimated breeding values as a dependent variable on 1,883 phenotyped animals that were ≥87.5% Holstein-Friesian. Putative susceptibility quantitative trait loci (QTL) were identified on Bos taurus autosome 1, 3, 5, 6, 8, 9, 10, 11, 13, 14, 18, 21, 23, 25, 26, 27, and 29; mapping the most significant SNP to genes within and overlapping these QTL revealed that the most significant associations were with the 10 functional candidate genes KALRN, ZBTB20, LPP, SLA2, FI3A1, LRCH3, DNAJC6, ZDHHC14, SNX1, and HAS2. Pathway analysis failed to reveal significantly enriched biological pathways, when both bovine-specific pathway data and human ortholog data were taken into account. The existence of genetic variation for MAP susceptibility in a large data set of dairy cows signifies the potential of breeding programs for reducing MAP susceptibility. Furthermore, the identification of susceptible QTL facilitates greater biological understanding of bovine paratuberculosis and potential therapeutic targets for future investigation. The novel molecular similarities identified between bovine paratuberculosis and human inflammatory bowel disease suggest potential for human therapeutic interventions to be translated to veterinary medicine and vice versa.     

Association of lipid-related genes implicated in conceptus elongation with female fertility traits in dairy cattle

Elongation of the preimplantation conceptus is a requirement for pregnancy success in ruminants, and failures in this process are highly associated with subfertility in dairy cattle. Identifying genetic markers that are related to early conceptus development and survival and utilizing these markers in selective breeding can improve the reproductive efficiency of dairy herds. Here, we evaluated the association of 1,679 SNP markers within or close to 183 candidate genes involved in lipid metabolism of the elongating conceptus with different fertility traits in US Holstein cattle. A total of 27,371 bulls with predicted transmitting ability records for daughter pregnancy rate, cow conception rate, and heifer conception rate were used as the discovery population. The associations found in the discovery population were validated using 2 female populations (1,122 heifers and 2,138 lactating cows) each with 4 fertility traits, including success to first insemination, number of services per conception, age at first conception for heifers, or days open for cows. Marker effects were estimated using a linear mixed model with SNP genotype as a linear covariate and a random polygenic effect. After multiple testing correction, 39 SNP flagging 27 candidate genes were associated with at least one fertility trait in the discovery population. Of these 39 markers, 3 SNP were validated in the heifer population and 4 SNP were validated in the cow population. The 3 SNP validated in heifers are located within or near genes CAT, MYOF, and RBP4, and the 4 SNP validated in lactating cows are located within or close to genes CHKA, GNAI1, and HMOX2. These validated genes seem to be relevant for reducing pregnancy losses, and the SNP within these genes are excellent candidates for inclusion in genomic tests to improve reproductive performance in dairy cattle.     

Short communication: Validation of somatic cell score–associated loci identified in a genome-wide association study in German Holstein cattle

Recently, we identified 6 genomic loci affecting daughter yield deviations (DYD) for somatic cell score (SCS) in a genome-wide association study (GWAS) performed with German Holstein bulls. In the current study, we tested if these loci were associated with SCS in cows using their own performance data. The study was performed with 1,412 German Holstein cows, of which 483 were daughters of 71 bulls that had been used in the GWAS. We tested 10 single nucleotide polymorphisms (SNP) representing 6 genomic regions that were associated with DYD for SCS in bulls. All tested SNP were significant in cows. Seven of them, located on Bos taurus autosomes (BTA) 6, 13, and 19, had the same direction of effect as those previously reported in the bull population. The most significant associations were detected on BTA6 and BTA19, accounting for 1.8% of the total genetic variance. The major allele of the 2 SNP on BTA6 and the minor allele of the 2 SNP on BTA19 were favorable for lower SCS. The differences between the homozygous genotype classes were up to 15,000 cells/mL. The verification of SNP associated with SCS in this study provides further evidence for the functional role of the linked genomic regions for immune response and contributes to identification of causative mutations. In particular, SNP with minor frequency of the favorable allele possess high potential to reduce SCS in German Holstein cattle by selection.     

Genome-wide association study for milk production traits in a Brazilian Holstein population

Advances in the molecular area of selection have expanded knowledge of the genetic architecture of complex traits through genome-wide association studies (GWAS). Several GWAS have been performed so far, but confirming these results is not always possible due to several factors, including environmental conditions. Thus, our objective was to identify genomic regions associated with traditional milk production traits, including milk yield, somatic cell score, fat, protein and lactose percentages, and fatty acid composition in a Holstein cattle population producing under tropical conditions. For this, 75,228 phenotypic records from 5,981 cows and genotypic data of 56,256 SNP from 1,067 cows were used in a weighted single-step GWAS. A total of 46 windows of 10 SNP explaining more than 1% of the genetic variance across 10 Bos taurus autosomes (BTA) harbored well-known and novel genes. The MGST1 (BTA5), ABCG2 (BTA6), DGAT1 (BTA14), and PAEP (BTA11) genes were confirmed within some of the regions identified in our study. Potential novel genes involved in tissue damage and repair of the mammary gland (COL18A1), immune response (LTTC19), glucose homeostasis (SLC37A1), synthesis of unsaturated fatty acids (LTBP1), and sugar transport (SLC37A1 and MFSD4A) were found for milk yield, somatic cell score, fat percentage, and fatty acid composition. Our findings may assist genomic selection by using these regions to design a customized SNP array to improve milk production traits on farms with similar environmental conditions.     

Identification of functional candidate variants and genes for feed efficiency in Holstein and Jersey cattle breeds using RNA-sequencing

The identification of functional genetic variants and associated candidate genes linked to feed efficiency may help improve selection for feed efficiency in dairy cattle, providing economic and environmental benefits for the dairy industry. This study used RNA-sequencing data obtained from liver tissue from 9 Holstein cows [n = 5 low residual feed intake (RFI), n = 4 high RFI] and 10 Jersey cows (n = 5 low RFI, n = 5 high RFI), which were selected from a single population of 200 animals. Using RNA-sequencing, 3 analyses were performed to identify: (1) variants within low or high RFI Holstein cattle; (2) variants within low or high RFI Jersey cattle; and (3) variants within low or high RFI groups, which are common across both Holstein and Jersey cattle breeds. From each analysis, all variants were filtered for moderate, modifier, or high functional effect, and co-localized quantitative trait loci (QTL) classes, enriched biological processes, and co-localized genes related to these variants, were identified. The overlapping of the resulting genes co-localized with functional SNP from each analysis in both breeds for low or high RFI groups were compared. For the first two analyses, the total number of candidate genes associated with moderate, modifier, or high functional effect variants fixed within low or high RFI groups were 2,810 and 3,390 for Holstein and Jersey breeds, respectively. The major QTL classes co-localized with these variants included milk and reproduction QTL for the Holstein breed, and milk, production, and reproduction QTL for the Jersey breed. For the third analysis, the common variants across both Holstein and Jersey breeds, uniquely fixed within low or high RFI groups were identified, revealing a total of 86,209 and 111,126 functional variants in low and high RFI groups, respectively. Across all 3 analyses for low and high RFI cattle, 12 and 31 co-localized genes were overlapping, respectively. Among the overlapping genes across breeds, 9 were commonly detected in both the low and high RFI groups (INSRR, CSK, DYNC1H1, GAB1, KAT2B, RXRA, SHC1, TRRAP, PIK3CB), which are known to play a key role in the regulation of biological processes that have high metabolic demand and are related to cell growth and regeneration, metabolism, and immune function. The genes identified and their associated functional variants may serve as candidate genetic markers and can be implemented into breeding programs to help improve the selection for feed efficiency in dairy cattle.     

A genome-wide association study for left-sided displacement of the abomasum using a high-density single nucleotide polymorphism array

Left-sided displacement of the abomasum (LDA) is a frequent disease in dairy cattle causing significant financial losses for dairy farmers. Heritability (h²) of this complex disease was estimated at up to 0.5 in German Holstein (GH) cattle. Using the Bovine High Density BeadChip (Illumina Inc., San Diego, CA) comprising 588,753 single nucleotide polymorphisms (SNP) after quality control for 126 LDA cases and 280 population-based controls, we used a mixed linear model analysis in a genome-wide association study (GWAS). We identified 6 genomic regions for LDA on bovine chromosomes 2, 8, 13, 20, 24, and X that were significantly associated with LDA. Each of these regions was covered by 4 to 12 LDA-associated SNP. Single SNP within these regions explained up to 7.3% of the phenotypic variance. An independent sample of 1,554 GH cows, including 539 controls and 1,015 cases, were genotyped for 8 SNP highly associated with LDA on Bos taurus autosomes (BTA) 2, 8, 13, and 24, as well as 6 SNP located in previously identified LDA regions on BTA1, 5, 11, and 27 using competitive allele-specific PCR genotyping technology (KASP). The analysis using the KASP genotypes confirmed LDA-associated loci on BTA2, 8, 13, and 27. These genomic regions may contribute to the susceptibility to LDA in Holstein cows and may harbor functional variants for LDA.     

Association analysis for young stock survival index with imputed whole-genome sequence variants in Nordic Holstein cattle

Identification of the genetic variants associated with calf survival in dairy cattle will aid in the elimination of harmful mutations from the cattle population and the reduction of calf and young stock mortality rates. We used de-regressed estimated breeding values for the young stock survival (YSS) index as response variables in a genome-wide association study with imputed whole-genome sequence variants. A total of 4,610 bulls with estimated breeding values were genotyped with the Illumina BovineSNP50 (Illumina, San Diego, CA) single nucleotide polymorphism (SNP) genotyping array. Genotypes were imputed to whole-genome sequence variants. After quality control, 15,419,550 SNP on 29 Bos taurus autosomes (BTA) were used for association analysis. A modified mixed-model association analysis was used for a genome scan, followed by a linear mixed-model analysis for selected genetic variants. We identified 498 SNP on BTA5 and BTA18 that were associated with the YSS index in Nordic Holstein. The SNP rs440345507 (Chr5:94721790) on BTA5 was the putative causal mutation affecting YSS. Two haplotype-based models were used to identify haplotypes with the largest detrimental effects on YSS index. For each association signal, 1 haplotype region with harmful effects and the lead associated SNP were identified. Detected haplotypes on BTA5 and BTA18 explained 1.16 and 1.20%, respectively, of genetic variance for the YSS index. We examined whether YSS quantitative trait loci (QTL) on BTA5 and BTA18 were associated with stillbirth. YSS QTL on BTA18 overlapped a QTL region for stillbirth, but most likely 2 different causal variants were responsible for these 2 QTL. Four component traits of the YSS index, defined by sex and age, were analyzed separately by the modified mixed-model approach. The same genomic regions were associated with both bull and heifer calf mortality. Several genes (EPS8, LOC100138951, and KLK family genes) contained a lead associated SNP or were included in haplotypes with large detrimental effects on YSS in Nordic Holstein cattle.     

Short communication: Effects of the progesterone receptor variants on fertility traits in cattle

The progesterone receptor (PGR) gene is a key factor in the initiation and maintenance of pregnancy and in embryo development. Currently, it is unknown what variants of the PGR gene are related to fertility traits in cattle. Identification of such variants would allow the implementation of marker-assisted selection in breeding schemes. The objective of this study was to investigate the association of single nucleotide polymorphisms (SNP) of PGR with fertility traits in Holstein dairy cattle. An in vitro fertilization system was used to maximize the efficiency of the identification of genetic factors affecting fertility. This in vitro fertilization system would allow the assessment of fertilization and embryonic survival rates independently of influences from the uterine environment. A total of 5,566 fertilization attempts were performed, and a total of 3,679 embryos were produced using oocytes from 324 Holstein cows and semen from 10 Holstein bulls. Sequencing of pooled DNA samples from ovaries revealed an SNP (G/C) in intron 3 of PGR. A generalized linear model was used to analyze the association of this SNP with fertilization and embryonic survival rates for each ovary. Oocytes obtained from CC ovaries showed a 61% fertilization rate, compared with 68 and 69% for GC and GG ovaries, respectively. The survival rate of embryos produced from GG ovaries was 5 and 6% higher than that of GC and CC ovaries. These results indicate that the PGR SNP could be used in marker-assisted selection breeding programs in Holstein dairy cattle.     

On the genomic regions associated with milk lactose in Fleckvieh cattle

Lactose is a sugar uniquely found in mammals' milk and it is the major milk solid in bovines. Lactose yield (LY, kg/d) is responsible for milk volume, whereas lactose percentage (LP) is thought to be more related to epithelial integrity and thus to udder health. There is a paucity of studies that have investigated lactose at the genomic level in dairy cows. This paper aimed to improve our knowledge on LP and LY, providing new insights into the significant genomic regions affecting these traits. A genome-wide association study for LP and LY was carried out in Fleckvieh cattle by using bulls' deregressed estimated breeding values of first lactation as pseudo-phenotypes. Heritabilities of first-lactation test-day LP and LY estimated using linear animal models were 0.38 and 0.25, respectively. A total of 2,854 bulls genotyped with a 54K SNP chip were available for the genome-wide association study; a linear mixed model approach was adopted for the analysis. The significant SNP of LP were scattered across the whole genome, with signals on chromosomes 1, 2, 3, 7, 12, 16, 18, 19, 20, 28, and 29; the top 4 significant SNP explained 4.90% of the LP genetic variance. The signals were mostly in regions or genes with involvement in molecular intra- or extracellular transport; for example, CDH5, RASGEF1C, ABCA6, and SLC35F3. A significant region within chromosome 20 was previously shown to affect mastitis or somatic cell score in cattle. As regards LY, the significant SNP were concentrated in fewer regions (chromosomes 6 and 14), related to mastitis/somatic cell score, immune response, and transport mechanisms. The 5 most significant SNP for LY explained 8.45% of genetic variance and more than one-quarter of this value has to be attributed to the variant within ADGRB1. Significant peaks in target regions remained even after adjustment for the 2 most significant variants previously detected on BTA6 and BTA14. The present study is a prelude for deeper investigations into the biological role of lactose for milk secretion and volume determination, stressing the connection with genes regulating intra- or extracellular trafficking and immune and inflammatory responses in dairy cows. Also, these results improve the knowledge on the relationship between lactose and udder health; they support the idea that LP and its derived traits are potential candidates as indicators of udder health in breeding programs aimed to enhance cows' resistance to mastitis.     

Associations between CXCR1 polymorphisms and pathogen-specific incidence rate of clinical mastitis,test-day somatic cell count,and test-day milk yield

The CXCR1 gene plays an important role in the innate immunity of the bovine mammary gland. Associations between single nucleotide polymorphisms (SNP) CXCR1c.735C>G and c.980A>G and udder health have been identified before in small populations. A fluorescent multiprobe PCR assay was designed specifically and validated to genotype both SNP simultaneously in a reliable and cost-effective manner. In total, 3,106 cows from 50 commercial Flemish dairy herds were genotyped using this assay. Associations between genotype and detailed phenotypic data, including pathogen-specific incidence rate of clinical mastitis (IRCM), test-day somatic cell count, and test-day milk yield (MY) were analyzed. Staphylococcus aureus IRCM tended to associate with SNP c.735C>G. Cows with genotype c.735GG had lower Staph. aureus IRCM compared with cows with genotype c.735CC (rate ratio = 0.35, 95% confidence interval = 0.14–0.90). Additionally, a parity-specific association between Staph. aureus IRCM and SNP c.980A>G was detected. Heifers with genotype c.980GG had a lower Staph. aureus IRCM compared with heifers with genotype c.980AG (rate ratio = 0.15, 95% confidence interval = 0.04–0.56). Differences were less pronounced in multiparous cows. Associations between CXCR1 genotype and somatic cell count were not detected. However, MY was associated with SNP c.735C>G. Cows with genotype c.735GG out-produced cows with genotype c.735CC by 0.8 kg of milk/d. Results provide a basis for further research on the relation between CXCR1 polymorphism and pathogen-specific mastitis resistance and MY.     

Novel strategies to minimize progeny inbreeding while maximizing genetic gain using genomic information

In this study, 3 strategies for controlling progeny inbreeding in mating plans were compared. The strategies used information from pedigree inbreeding coefficients, genomic relationships, or shared runs of homozygosity. The strategies were compared for the reduction in genetic gain and progeny inbreeding that would be expected from selected matings, and for the decrease of homozygosity of deleterious recessive alleles. Using real pedigree, genotype [43,115 single nucleotide polymorphism (SNP) markers], and estimated breeding value data from Holstein cattle, mating plans were derived for herds of 300 cows with 20 sires available for mating, replicated 50 times. Each of the 300 individuals allocated as dams were matched to 1 of 20 sires to maximize genetic merit minus the penalty for estimated progeny inbreeding, and given the restriction that the sire could not be mated to more than 10% of the cows. The strategy that used a genomic relationship matrix (GRM) was the most effective in reducing average progeny inbreeding; this strategy also resulted in fewer homozygous SNP out of 1,000 low-frequency SNP compared with the strategy using pedigree information. In the future, large numbers of cattle may be genotyped for low-density SNP panels. A GRM constructed using 3,123 SNP produced results similar to a GRM constructed using the full 43,115 SNP. These results demonstrate that using GRM information, a 1% reduction in progeny inbreeding (valued at around $5 per cow) can be made with very little compromise in the overall breeding objective. These results and the availability of low-cost, low-density genotyping make it attractive to apply mating plans that use genomic information in commercial dairy herds.     

Genome-wide association study of normal and atypical progesterone profiles in Holstein-Friesian dairy cows

Female fertility has a major role in dairy production and affects the profitability of dairy cattle. The genetic progress obtained by traditional selection can be slow because of the low heritability of classical fertility traits. Endocrine fertility traits based on progesterone concentration in milk have higher heritability and more directly reflect the cow's own reproductive physiology. The aim of our study was to identify genomic regions for 7 endocrine fertility traits in dairy cows by performing a genome-wide association study with 54,000 SNP. The next step was to fine-map targeted genomic regions with significant SNP using imputed sequences to identify potential candidate genes associated with the normal and atypical progesterone profiles. The association between a SNP and a phenotype was assessed by a single SNP analysis, using a linear mixed model that included a random polygenic effect. Phenotypes and genotypes were available for 1,126 primiparous and multiparous Holstein-Friesian cows from research herds in Ireland, the Netherlands, Sweden, and the United Kingdom. In total, 44 significant SNP associated with 7 endocrine fertility traits were identified on Bos taurus autosome (BTA) 1–4, 6, 8–9, 11–12, 14–17, 19, 21–24, and 29. Three chromosomes, BTA8, BTA17, and BTA23, were imputed from 54,000 SNP genotypes to the whole-genome sequence level with Beagle version 4.1. The fine-mapping identified several significant associations with delayed cyclicity, cessation of cyclicity, commencement of luteal activity, and inter-ovulatory interval. These associations may contribute to an index of markers for genetic improvement of fertility. Several potential candidate genes reported to affect reproduction were also identified in the targeted genomic regions. However, due to high linkage disequilibrium, it was not possible to identify putative causal genes or polymorphisms for any of the regions.     

Estimation of genetic parameters and single-step genome-wide association studies for milk urea nitrogen in Holstein cattle

The main objectives of this study were to estimate genetic parameters for milk urea nitrogen (MUN) in Holstein cattle and to conduct a single-step (ss)GWAS to identify candidate genes associated with MUN. Phenotypic measurements from 24,435 Holstein cows were collected from March 2013 to July 2019 in 9 dairy farms located in the Beijing area, China. A total of 2,029 cows were genotyped using the Illumina 150K Bovine Bead Chip, containing 121,188 SNP. A single-trait repeatability model was used to evaluate the genetic background of MUN. We found that MUN is a trait with low heritability (0.06 ± 0.004) and repeatability (0.12). Considering similar milk production levels, a lower MUN concentration indicates higher nitrogen digestibility. The genetic correlations between MUN and milk yield, net energy concentration, fat percentage, protein percentage, and lactose percentage were positive and ranged from 0.02 to 0.26. The genetic correlation between MUN and somatic cell score (SCS) was negative (?0.18), indicating that animals with higher MUN levels tend to have lower SCS. Both ssGWAS and pathway enrichment analyses were used to explore the genetic mechanisms underlying MUN. A total of 18 SNP (located on BTA11, BTA12, BTA14, BTA17, and BTA18) were found to be significantly associated with MUN. The genes CFAP77, CAMSAP1, CACNA1B, ADGRB1, FARP1, and INTU are considered to be candidate genes for MUN. These candidate genes are associated with important biological processes such as protein and lipid metabolism and binding to specific proteins. This set of candidate genes, metabolic pathways, and their functions provide a better understanding of the genomic architecture and physiological mechanisms underlying MUN in Holstein cattle.     

Proofs for genotype by environment interactions considering pedigree and genomic data from organic and conventional cow reference populations

The aim of the present study was to prove genotype by environment interactions (G × E) for production, longevity, and health traits considering conventional and organic German Holstein dairy cattle subpopulations. The full data set included 141,778 Holstein cows from 57 conventional herds and 7,915 cows from 9 organic herds. The analyzed traits were first-lactation milk yield and fat percentage (FP), the length of productive life (LPL) and the health traits mastitis, ovarian cycle disorders, and digital dermatitis in first lactation. A subset of phenotyped cows was genotyped and used for the implementation of separate cow reference populations. After SNP quality controls, the cow reference sets considered 40,830 SNP from 19,700 conventional cows and the same 40,830 SNP from 1,282 organic cows. The proof of possible G × E was made via multiple-trait model applications, considering same traits from the conventional and organic population as different traits. In this regard, pedigree (A), genomic (G) and combined relationship (H) matrices were constructed. For the production traits, heritabilities were very similar in both organic and conventional populations (i.e., close to 0.70 for FP and close to 0.40 for milk yield). For low heritability health traits and LPL, stronger heritability fluctuations were observed, especially for digital dermatitis with 0.05 ± 0.01 (organic, A matrix) to 0.33 ± 0.04 (conventional, G matrix). Quite large genetic correlations between same traits from the 2 environments were estimated for production traits, especially for high heritability FP. For LPL, the genetic correlation was 0.67 (A matrix) and 0.66 (H matrix). The genetic correlation between LPL organic with LPL conventional was 0.94 when considering the G matrix, but only 213 genotyped cows were included. For health traits, genetic correlations were throughout lower than 0.80, indicating possible G × E. Genetic correlations from the different matrices A, G, and H for health and production traits followed the same pattern, but the estimates from G for health traits were associated with quite large standard errors. In genome-wide association studies, significantly associated SNP for production traits overlapped in the conventional and organic population. In contrast, for low heritability LPL and health traits, significantly associated SNP and annotated potential candidate genes differed in both populations. In this regard, significantly associated SNP for mastitis from conventional cows were located on Bos taurus autosomes 6 and 19, but on Bos taurus autosomes 1, 10, and 22 in the organic population. For the remaining health traits and LPL, different potential candidate genes were annotated, but the different genes reflect similar physiological pathways. We found evidence of G × E for low heritability functional traits, suggesting different breeding approaches in organic and conventional populations. Nevertheless, for a verification of results and implementation of alternative breeding strategies, it is imperative to increase the organic cow reference population.     

Genetic parameters and weighted single-step genome-wide association study for supernumerary teats in Holstein cattle

Supernumerary teats (SNT) are a common epidermal abnormality of udders in mammals. The SNT negatively affect machine milking ability, udder health, and animal welfare and sometimes act as reservoirs for undesirable bacteria, resulting in economic losses on calves and lactating cows due to the cost of SNT removal surgery, early culling, and low milk yield. This study aimed to analyze the incidence and genetic parameter of SNT and detect SNT-related genes in Chinese Holstein cattle. In this study, the incidence of SNT was recorded in 4,670 Chinese Holstein cattle (born between 2008 and 2017) from 2 farms, including 734 genotyped cows with 114,485 SNPs. The SNT had a total frequency of 9.8% and estimated heritability of 0.22 (SE = 0.07), which were obtained using a threshold model in the studied Chinese Holstein population. Furthermore, we calculated approximate genetic correlations between SNT and the following indicator traits: 12 milk production, 28 body conformation, 5 fertility and reproduction, 5 health, and 9 longevity. Generally, the estimated correlations, such as 305-d milk yield for third parity (−0.55; SE = 0.02) and age at first calving in heifer (0.19; SE = 0.03), were low to moderate. A single-step GWAS was implemented, and 10 genes associated with SNT located in BTA4 were identified. The region (112.70–112.90 Mb) on BTA4 showed the highest genetic variance for SNT. The quantitative trait loci on BTA4 was mapped into the RARRES2 gene, which was previously shown to affect adipogenesis and hormone secretion. The WIF1 gene, which was located in BTA5, was also considered as a candidate gene for SNT. Overall, these findings provide useful information for breeders who are interested in reducing SNT.     

Production effects of pathogens causing bovine leukosis, bovine viral diarrhea, paratuberculosis, and neosporosis

The primary purpose of this research was to determine associations among seropositivity for bovine leukemia virus (BLV), bovine viral diarrhea virus (BVDV), Mycobacterium avium ssp. paratuberculosis (MAP), and Neospora caninum (NC) and each of 3 outcome variables (305-d milk, fat, and protein production) in Canadian dairy cattle. Serum samples from up to 30 randomly selected cows from 342 herds on monthly milk testing were tested for antibodies against BLV (IDEXX ELISA; IDEXX Corporation, Westbrook, ME), MAP (IDEXX or Biocor ELISA; Biocor Animal Health, Inc., Omaha, NE), and NC (IDEXX or Biovet ELISA; Biovet Inc., St. Hyacinthe, Quebec, Canada). Up to 5 unvaccinated cattle over 6 mo of age were tested for virus-neutralizing antibodies to the Singer strain of type 1 BVDV. Dairy Herd Improvement records were obtained electronically for all sampled cows. Linear mixed models with herd and cow as random variables were fit, with significant restricted maximum likelihood estimates of outcome effects being obtained, while controlling for potential confounding variables. Bovine leukemia virus seropositivity was not associated with 305-d milk, 305-d fat, or 305-d protein production. Cows in BVDV-seropositive herds (at least one unvaccinated animal with a titer ≥1:64) had reductions in 305-d milk, fat, and protein of 368, 10.2, and 9.5 kg, respectively, compared with cows in BVDV-seronegative herds. Mycobacterium avium ssp. paratuberculosis seropositivity was associated with lower 305-d milk of 212 kg in 4+-lactation cows compared with MAP-seronegative 4+-lactation cows. Neospora caninum seropositivity in primiparous cows was associated with lower 305-d milk, fat, and protein of 158, 5.5, and 3.3 kg, respectively, compared with NC-seronegative primiparous cows. There were no interactions among seropositivity for any of the pathogens and their effects on any of the outcomes examined, although the low MAP seroprevalence limited this analysis. Results from this research will contribute to understanding the economic impacts of these pathogens and justify their control.     

Controlling bovine leukemia virus in dairy herds by identifying and removing cows with the highest proviral load and lymphocyte counts

The objective of this field trial was to reduce bovine leukemia virus (BLV) transmission and prevalence in commercial dairy herds using proviral load (PVL) and lymphocyte count (LC) measurements as indicators of the most infectious animals for culling or segregation. Bovine leukemia virus causes lymphoma in <5% of infected cattle, and increased lymphocyte counts (lymphocytosis) in about one-third. Recent research has shown that dairy cows infected with BLV have altered immune function associated with decreases in milk production and lifespan. Recent findings show that a minority of infected cattle have PVL concentrations in blood and other body fluids of over 1,000 times that of other infected cattle. In combination with a high LC, these animals are thought to be responsible for most transmission of BLV in a herd. Milk or blood samples from adult cows in our 3 Midwestern dairy farm field trials were tested semiannually with ELISA for BLV antibodies, and ELISA-positive cattle were then retested using a blood LC and a quantitative PCR test for PVL to identify the animals presumed to be most infectious. Herd managers were encouraged to consider PVL and LC status when making cull decisions, and to segregate cows with the highest PVL and LC from their BLV ELISA-negative herd mates where possible. After 2 to 2.5 yr of this intervention, the incidence risk of new infections decreased in all 3 herds combined, from 13.8 to 2.2, and the overall herd prevalence decreased in all 3 herds combined from 62.0 to 20.7%, suggesting that this approach can efficiently reduce BLV transmission as well as prevalence. This is encouraging, because a very low prevalence of BLV infection would make it economically feasible to cull the remaining ELISA-positive cattle, as was achieved in national eradication programs in other countries decades ago.