Association between single nucleotide polymorphisms in the CXCR1 gene and somatic cell score in Holstein dairy cattle

In addition to its position in a quantitative trait locus for somatic cell score (SCS) and its function in the immune response, the CXCR1 chemokine receptor gene located on Bos taurus autosome 2 is an auspicious candidate gene for udder health in dairy cattle. An association analysis was conducted in the German Holstein-Friesian population to test the association between the single nucleotide polymorphism (SNP) at position +777 within the CXCR1 gene and the SNP at position −1768 in the 5′ upstream region of this gene (rs41255711) and the indicator trait SCS by using a granddaughter design. Data were analyzed for 3 families, with a total of 749 genotyped bulls and an extended pedigree of 8,071 animals from the national German bovine genome mapping project. Variance component estimation was used to determine the source of phenotypic variation in the chromosomal area of interest. A 20-cM window surrounding the 2 SNP in the CXCR1 gene was examined. Although the percentage of variance caused by the putative quantitative trait locus in the area studied was relatively large (12 and 11%, respectively), no statistically significant association of the SNP CXCR1+777 or CXCR1−1768 with SCS was found. These results contradict previously published studies.     

Short communication: Genetic association of variations in the osteopontin gene (SPP1) with lactation persistency in dairy cattle

Improving lactation persistency (LP) in dairy cattle has a beneficial effect on animal health and fertility and herd productivity. A complex trait, LP not only reflects the cow's ability to maintain milk secretion activity after the lactation peak but is also a function of the postcalving development of the mammary gland and, later on, of tissue remodeling as lactation declines. This decline is a consequence of an imbalance between cell proliferation and cell removal. In a previous study, single nucleotide polymorphisms were identified in the osteopontin (OPN) gene, SPP1. Osteopontin is a multifaceted protein that plays an important role in immune regulation and tissue remodeling. Because OPN is involved in involution, it might also have an effect on LP. The objective of the present study was to evaluate whether LP could be influenced by genetic variations in the SPP1 gene. This association with LP was analyzed in the population of 578 bulls characterized in a previous study. The population mean of estimated breeding value (EBV) for LP was 100.95 ± 5.06 units. Allele and genotype association analyses were performed by comparing the frequencies of the different genotypes and alleles with EBV for LP for the respective lactation using logistic regression. The EBV for LP at the first lactation (LP1), second lactation (LP2), and third lactation (LP3) and for overall lactation (OLP) are reported for the genotypes SPP1c.-1301G>A, SPP1c.-1251C>T, SPP1c.-430G>A, and SPP1c.*40A>C. The first single nucleotide polymorphism, SPP1c.-1301G>A, affected LP1, LP2, LP3, and OLP. Analysis of the estimated average allele substitution effects also confirmed that G is a favorable allele for LP, given the gain observed over LP1, LP2, LP3, and OLP. Differences in EBV for LP were observed between animals with different haplotypes at LP1, LP2, LP3, and OLP. Contrast analysis for OLP revealed that mean EBV is greater for block H1 (101.34 ± 0.30) than for animals that do not have H1 (98.20 ± 0.77). The gain with block H1 (GCGA) suggests the presence of the favorable allele G (first position in the block: SPP1c.-1301G). The pleiotropic roles of OPN position it at the crossroads of immune regulation, tissue remodeling, and involution. From a genetic perspective, data from the present study suggest OPN as a candidate gene associated with LP for dairy cows.     

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.     

Identification of single nucleotide polymorphisms in the bovine interleukin-12 and interleukin-23 receptor genes and their associations with health and production traits in Holstein cows

Interleukin-12 (IL-12) and interleukin-23 (IL-23) are proinflammatory cytokines produced by macrophages and dendritic cells in response to infection with intracellular pathogens. The IL-12 receptor (IL-12R) is a heterodimer composed of 2 subunits, β1 and β2. The IL-23 receptor (IL-23R) is a heterodimer composed of the IL-12Rβ1 subunit and a unique IL-23R subunit. Given the importance of IL-12 and IL-23 for modulating inflammation and the host immune response, the IL-12 and IL-23 receptor genes may be suitable candidate genes for studying disease resistance in dairy cattle. We hypothesize that single nucleotide polymorphisms (SNP) exist within these genes and that they contribute to variation in health and production traits in dairy cattle. To investigate this, a selective DNA pool was constructed using bull semen based on the estimated breeding values for somatic cell score (SCS), an indicator trait used to achieve genetic improvement for resistance to mastitis. Gene segments were amplified from this pool by PCR and the amplicons were sequenced to reveal SNP. A total of 10 SNP, including 2 in IL-12Rβ1, 5 in IL-12Rβ2, and 3 in IL-23R were identified. The SNP (n = 5) were found in the 5′ untranslated region (UTR) putative promoter regions of the genes, and SNP IL-23R c.1714A > C was a nonsynonymous SNP. Canadian Holstein bulls (n = 492) were genotyped using Sequenom MassARRAY (Sequenom Inc., San Diego, CA). No association was found with SCS based on bull deregressed estimated breeding values for SCS; however, associations of SNP in the IL-12Rβ2 gene (c.-511A > G, c.87A > G, c.2957A > C) were found with milk and protein yield. Further investigation will be required to elucidate the biological and practical relevance of these SNP.     

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.     

Short communication: Genetic variability in the predicted microRNA target sites of caprine casein genes

The main goal of the current work was to identify single nucleotide polymorphisms (SNP) that might create or disrupt microRNA (miRNA) target sites in the caprine casein genes. The 3′ untranslated regions of the goat α_S1-, α_S2-, β-, and κ-casein genes (CSN1S1, CSN1S2, CSN2, and CSN3, respectively) were resequenced in 25 individuals of the Murciano-Granadina, Cashmere, Canarian, Saanen, and Sahelian breeds. Five SNP were identified through this strategy: c.*175C > T at CSN1S1; c.*109T > C, c.*139G > C, and c.*160T > C at CSN1S2; and c.*216C > T at CSN2. Analysis with the Patrocles Finder tool predicted that all of these SNP are located within regions complementary to the seed of diverse miRNA sequences. These in silico results suggest that polymorphism at miRNA target sites might have some effect on casein expression. We explored this issue by genotyping the c.*175C > T SNP (CSN1S1) in 85 Murciano-Granadina goats with records for milk CSN1S1 concentrations. This substitution destroys a putative target site for miR-101, a miRNA known to be expressed in the bovine mammary gland. Although TT goats had higher levels (6.25 g/L) of CSN1S1 than their CT (6.05 g/L) and CC (6.04 g/L) counterparts, these differences were not significant. Experimental confirmation of the miRNA target sites predicted in the current work and performance of additional association analyses in other goat populations will be an essential step to find out if polymorphic miRNA target sites constitute an important source of variation in casein expression.     

Genomic analysis of cow mortality and milk production using a threshold-linear model

The objective of this study was to investigate the feasibility of genomic evaluation for cow mortality and milk production using a single-step methodology. Genomic relationships between cow mortality and milk production were also analyzed. Data included 883,887 (866,700) first-parity, 733,904 (711,211) second-parity, and 516,256 (492,026) third-parity records on cow mortality (305-d milk yields) of Holsteins from Northeast states in the United States. The pedigree consisted of up to 1,690,481 animals including 34,481 bulls genotyped with 36,951 SNP markers. Analyses were conducted with a bivariate threshold-linear model for each parity separately. Genomic information was incorporated as a genomic relationship matrix in the single-step BLUP. Traditional and genomic estimated breeding values (GEBV) were obtained with Gibbs sampling using fixed variances, whereas reliabilities were calculated from variances of GEBV samples. Genomic EBV were then converted into single nucleotide polymorphism (SNP) marker effects. Those SNP effects were categorized according to values corresponding to 1 to 4 standard deviations. Moving averages and variances of SNP effects were calculated for windows of 30 adjacent SNP, and Manhattan plots were created for SNP variances with the same window size. Using Gibbs sampling, the reliability for genotyped bulls for cow mortality was 28 to 30% in EBV and 70 to 72% in GEBV. The reliability for genotyped bulls for 305-d milk yields was 53 to 65% to 81 to 85% in GEBV. Correlations of SNP effects between mortality and 305-d milk yields within categories were the highest with the largest SNP effects and reached >0.7 at 4 standard deviations. All SNP regions explained less than 0.6% of the genetic variance for both traits, except regions close to the DGAT1 gene, which explained up to 2.5% for cow mortality and 4% for 305-d milk yields. Reliability for GEBV with a moderate number of genotyped animals can be calculated by Gibbs samples. Genomic information can greatly increase the reliability of predictions not only for milk but also for mortality. The existence of a common region on Bos taurus autosome 14 affecting both traits may indicate a major gene with a pleiotropic effect on milk and mortality.     

Identification of single nucleotide polymorphisms in the bovine solute carrier family 11 member 1 (SLC11A1) gene and their association with infection by Mycobacterium avium subspecies paratuberculosis

Johne's disease is a chronic enteritis caused by Mycobacterium avium ssp. paratuberculosis (MAP) that causes substantial financial losses for the cattle industry. Susceptibility to MAP infection is reported to be determined in part by genetic factors, so marker-assisted selection could help to obtain bovine populations that are increasingly resistant to MAP infection. Solute carrier family 11 member 1 (SLC11A1) was adjudged to be a potential candidate gene because of its role in innate immunity, its involvement in susceptibility to numerous intracellular infections, and its previous association with bovine MAP infection. The objectives of this study were to carry out an exhaustive process of discovery and compilation of polymorphisms in SLC11A1 gene, and to perform a population-based genetic association study to test its implication in susceptibility to MAP infection in cattle. In all, 57 single nucleotide polymorphisms (SNP) were detected, 25 of which are newly described in Bos taurus. Twenty-four SNP and two 3′-untranslated region polymorphisms, previously analyzed, were selected for a subsequent association study in 558 European Holstein-Friesian animals. The SNP c.1067C > G and c.1157-91A > T and a haplotype formed by these 2 SNP yielded significant association with susceptibility to MAP infection. The c.1067C > G is a nonsynonymous SNP that causes an amino acid change in codon 356 from proline to alanine (P356A) that could alter SLC11A1 protein function. This association study supports the involvement of SLC11A1 gene in susceptibility to MAP infection in cattle. Our results suggest that SNP c.1067C > G may be a potential causal variant, although functional studies are needed to assure this point.     

Consumption of high energy maize diets is associated with increased soluble collagen in muscle of Holstein bulls

The aim was to investigate whether energy supplementation of gazing bulls can influence collagen concentration and solubility in three different muscles: longissimus dorsi (LD), semitendinosus (ST) and supraspinatus (SS). Thirty three Holstein bulls aged 15 months and reared on grass, were randomly assigned to three treatment groups for 85 days: fed grass ad libitum (G1-control); fed grass ad libitum and supplemented with 4 kg day^− 1 of ground maize (G2); fed grass ad libitum and supplemented with 8 kg day^− 1 of ground maize (G3). Total collagen content did not differ (P > 0.05) among treatments, however, soluble (heat-labile) collagen was significantly (P < 0.001) higher in meat from G3 (34%, 23% and 25% for LD, ST and SS, respectively), compared with G1-control (24%, 18% and 17% in LD, ST and SS, respectively). Overall, these results suggest that meat tenderness of grazing bulls may be improved by supplementing with ground maize (8 kg day^− 1).     

Selection on yield and fitness traits when culling holsteins during the first three lactations

Emphasis by dairy producers on various yield and fitness traits when culling cows was documented for US Holstein calvings since 1982. Least squares differences between cows retained for additional parities and those culled were estimated for milk, fat, and protein yields; somatic cell score (SCS); days open (DO); dystocia score (DS), final score (FS), and 14 type traits. Compared with cows culled during first lactation, superiority for first-parity milk yield was 569 to 1,175 kg for cows with 2 lactations, 642 to 1,283 kg for cows with ≥2 lactations, 710 to 1,350 kg for cows with 3 lactations, and 663 to 1,331 kg for cows with ≥4 lactations. Cows retained for ≥2 lactations had first-parity SCS that were 0.34 to 0.62 lower (more favorable) than those of cows culled during first lactation; first-parity SCS for cows retained for 3 or ≥4 lactations were even more favorable than those of cows with 1 or 2 lactations. The negative genetic relationship between yield and fertility contributed to increased DO as selection for higher milk yield persisted across time despite considerable preference for early conception when culling cows. In 1982, cows retained in the herd for 2, 3, and ≥4 lactations conceived earlier during first lactation (19, 17, and 23 fewer DO, respectively) than those culled during first lactation; those differences had increased to 34, 41, and 52 fewer DO by 2000. Although DS has a negative relationship with survival, first-parity DS were only slightly lower (by 0.10 to 0.14) for survivors than for cows culled during first lactation. Cows retained for ≥2 lactations had greater first-parity FS by 1.4 to 1.9 points than those culled during first lactation. On a standardized basis, the most intense selection during first lactation was for milk and protein yields with less for fat (74 to 86% of that for milk), DO (18 to 74%), FS (22 to 38%), SCS (19 to 37%), and DS (7 to 15%). Producers continued to emphasize the same traits when culling during second and third lactations. Trait priority by producers during culling could aid in setting trait emphasis when selecting bulls for progeny test and could also be useful in developing software for index-based culling guides.     

Comparison between a sire model and an animal model for genetic evaluation of fertility traits in Danish Holstein population

Comparisons between a sire model, a sire-dam model, and an animal model were carried out to evaluate the ability of the models to predict breeding values of fertility traits, based on data including 471,742 records from the first lactation of Danish Holstein cows, covering insemination years from 1995 to 2004. The traits in the analysis were days from calving to first insemination, calving interval, days open, days from first to last insemination, number of inseminations per conception, and nonreturn rate within 56 d after first service. The correlations between sire estimated breeding value (EBV) from the animal model and the sire-dam model were close to 1 for all the traits, and those between the animal model and the sire model ranged from 0.95 to 0.97. Model ability to predict sire breeding value was assessed using 4 criteria: 1) the correlation between sire EBV from 2 data subsets (DATA_A and DATA_B); 2) the correlation between sire EBV from training data (DATA_A or DATA_B) and yield deviation from test data (DATA_B or DATA_A) in a cross-validation procedure; 3) the correlation between the EBV of proven bulls, obtained from the whole data set (DATA_T) and from a reduced set of data (DATA_C1) that contained only the first-crop daughters of sires; and 4) the reliability of sire EBV, calculated from the prediction error variance of EBV. All criteria used showed that the animal model was superior to the sire model for all the traits. The sire-dam model performed as well as the animal model and had a slightly smaller computational demand. Averaged over the 6 traits, the correlations between sire EBV from DATA_A and DATA_B were 0.61 (sire model) versus 0.64 (animal model), the correlations between EBV from DATA_T and DATA_C1 for proven bulls were 0.59 versus 0.67, the correlations between EBV and yield deviation in the cross-validation were 0.21 versus 0.24, and the reliabilities of sire EBV were 0.42 versus 0.46. Model ability to predict cow breeding value was measured by the reliability of cow EBV, which increased from 0.21 using the sire model to 0.27 using the animal model. All the results suggest that the animal model, rather than the sire model, should be used for genetic evaluation of fertility traits.     

Random regression test-day model for clinical mastitis: Genetic parameters,model comparison,and correlations with indicator traits

The objective was to study genetic (co)variance components for binary clinical mastitis (CM), test-day protein yield, and udder health indicator traits [test-day somatic cell score (SCS) and type traits of the udder composite] in the course of lactation with random regression models (RRM). The study used a data set from selected 15 large-scale contract herds including 26,651 Holstein cows. Test-day production and CM data were recorded from 2007 to 2012 and comprised parities 1 to 3. A longitudinal CM data structure was generated by assigning CM records to adjacent official test dates. Bivariate threshold-linear RRM were applied to estimate genetic (co)variance components between longitudinal binary CM (0 = healthy; 1 = diseased) and longitudinal Gaussian distributed protein yield and SCS test-day data. Heritabilities for liability to CM (heritability ~0.15 from 0 to 305 d after calving) were slightly higher than for SCS for corresponding days in milk (DIM) in the course of lactation. Daily genetic correlations between CM and SCS were moderate to high (genetic correlation ~0.70), but substantially decreased at the very end of lactation. Genetic correlations between CM at different test days were close to 1 for adjacent test days, but were close to zero for test days far apart. Daily genetic correlations between CM and protein yield were low to moderate. For identical DIM (e.g., DIM 20, 160, and 300), genetic correlations were −0.03, 0.11, and 0.18, respectively, and disproved pronounced genetic antagonisms between udder health and productivity. Correlations between estimated breeding values (EBV) for CM from the RRM and official EBV for linear type traits of the udder composite, including EBV from 74 influential sires (sires with >60 daughters), were −0.31 for front teat placement, −0.01 for rear teat placement, −0.31 for fore udder attachment, −0.32 for udder depth, and −0.08 for teat length. Estimated breeding values for CM from the RRM were compared with EBV from a multiple-trait model and with EBV from a repeatability model. For test days covering an identical time span and on a lactation level, correlations between EBV from RRM, multiple-trait model, and repeatability model were close to 1. Most relevant results suggest the routine application of threshold RRM to binary CM to (1) allow selection of genetically superior sires for distinct stages of lactation and (2) achieve higher selection response in CM compared with selection strategies based on indicator type traits or based on the indicator-trait SCS.     

Genetic evaluation and best prediction of lactation persistency

Cows with high persistency tend to produce less milk than expected at the beginning of lactation and more than expected at the end. Best prediction of persistency was calculated as a function of a trait-specific standard lactation curve and a linear regression of test-day deviations on days in milk. Regression coefficients were deviations from a balance point to make yield and persistency phenotypically uncorrelated. The objectives of this study were to calculate (co)variance components and breeding values for best predictions of persistency of milk (PM), fat (PF), protein (PP), and SCS (PSCS) in Holstein cows. Data included 8,682,138 lactations from 4,375,938 cows calving since 1997, and 39,354 sires were evaluated. Sire estimated breeding values (EBV) for PM, PF, and PP were similar and ranged from −0.70 to 0.75 for PM; EBV for PSCS ranged from −0.37 to 0.28. Regressions of sire EBV on birth year were near zero (<0.003) but positive for PM, PF, and PP, and negative for PSCS. Genetic correlations of PM, PF, and PP with PSCS were moderate and favorable, indicating that increasing SCS decreases yield traits, as expected. Genetic correlations among yield and persistency were low to moderate and ranged from −0.09 (PSCS) to 0.18 (PF). This definition of persistency may be more useful than those used in test-day models, which are often correlated with yield. Routine genetic evaluations for persistency are feasible and may allow for improved predictions of yield traits. As calving intervals increase, persistency may have greater value.     

Short communication: Jersey × Holstein crossbreds compared with pure Holsteins for production, mastitis, and body measurements during the first 3 lactations

Jersey (JE) × Holstein (HO) crossbred cows (n = 76) were compared with pure HO cows (n = 73) for 305-d milk, fat, and protein production, somatic cell score (SCS), clinical mastitis, lifetime production, and body measurements during their first 3 lactations. Cows were in 2 research herds at the University of Minnesota and calved from September 2003 to June 2008. Best prediction was used to determine actual production for 305-d lactations as well as lifetime production (to 1,220 d in the herd after first calving) from test-day observations. During first lactation, JE × HO cows and pure HO cows were not significantly different for fat plus protein production; however, JE × HO cows had significantly lower fat plus protein production during second (−25 kg) and third (−51 kg) lactation than pure HO cows. Nevertheless, JE × HO cows were not significantly different from pure HO cows for lifetime production or lifetime SCS. The JE × HO cows were not significantly different from pure HO cows for SCS and clinical mastitis during first and second lactations; however, JE × HO cows tended to have higher SCS (3.79) than pure HO cows (3.40), but significantly lower (−23.4%) clinical mastitis during third lactation. The JE × HO cows had significantly less hip height, smaller heart girth, less thurl width, and less pin width than pure HO cows during the first 3 lactations. Furthermore, JE × HO cows had significantly less udder clearance from the ground and significantly greater distance between the front teats than pure HO cows during their first 3 lactations.     

Relationships between milk yield and somatic cell score in Canadian Holsteins from simultaneous and recursive random regression models

Multiple-trait random regression animal models with simultaneous and recursive links between phenotypes for milk yield and somatic cell score (SCS) on the same test day were fitted to Canadian Holstein data. All models included fixed herd test-day effects and fixed regressions within region-age at calving-season of calving classes, and animal additive genetic and permanent environmental regressions with random coefficients. Regressions were Legendre polynomials of order 4 on a scale from 5 to 305 d in milk (DIM). Bayesian methods via Gibbs sampling were used for the estimation of model parameters. Heterogeneity of structural coefficients was modeled across (the first 3 lactations) and within (4 DIM intervals) lactation. Model comparisons in terms of Bayes factors indicated the superiority of simultaneous models over the standard multiple-trait model and recursive parameterizations. A moderate heterogeneous (both across- and within-lactation) negative effect of SCS on milk yield (from −0.36 for 116 to 265 DIM in lactation 1 to −0.81 for 5 to 45 DIM in lactation 3) and a smaller positive reciprocal effect of SCS on milk yield (from 0.007 for 5 to 45 DIM in lactation 2 to 0.023 for 46 to 115 DIM in lactation 3) were estimated in the most plausible specification. No noticeable differences among models were detected for genetic and environmental variances and genetic parameters for the first 2 regression coefficients. The curves of genetic and permanent environmental variances, heritabilities, and genetic and phenotypic correlations between milk yield and SCS on a daily basis were different for different models. Rankings of bulls and cows for 305-d milk yield, average daily SCS, and milk lactation persistency remained the same among models. No apparent benefits are expected from fitting causal phenotypic relationships between milk yield and SCS on the same test day in the random regression test-day model for genetic evaluation purposes.     

Association of the OLR1 gene with milk composition in Holstein dairy cattle

Oxidized low-density lipoprotein receptor (OLR1) is the major protein that binds, internalizes, and degrades oxidized low-density lipoprotein. The role of OLR1 in lipid metabolism and the results of previous whole-genome scan studies prompted the investigation of OLR1 as a candidate gene affecting milk composition traits. Direct cDNA and genomic sequencing of OLR1 revealed 2 single nucleotide polymorphisms (SNP) in exon 4, 5 SNP in intron 4, and 1 in the 3′ untranslated region (UTR). Four intragenic haplotypes comprising SNP positions 7,160, 7,161, 7,278, 7,381, 7,409, 7,438, 7,512, and 8,232 were inferred. Haplotype analysis showed that one of the haplotypes was associated with a significant increase in fat yield and fat percentage. Single SNP analysis showed that allele C of SNP 8,232 (in the 3′-UTR) had significant effects on fat yield and fat percentage, whereas SNP 7,160 and 7,161 (in exon 4) had no significant effects. Both single SNP and haplotype analyses indicate that SNP 8,232 in the 3′-UTR is associated with milk fat yield and percentage and it may be in linkage disequilibrium with the functional polymorphism. To provide support for the hypothesis that SNP 8,232 is responsible for OLR1 expression, OLR1 expression levels in individuals bearing different genotypes were assessed. It was found that OLR1 expression was reduced in genotype AA individuals compared with CC and AC individuals, suggesting that A at position 8,232 may be the nucleotide causing decreased OLR1 expression. The 3′-UTR polymorphism found in this study might control translation or stability of OLR1 mRNA.     

Extent of linkage disequilibrium in Holstein cattle in North America

The success of fine-scale mapping and genomic selection depends mainly on the strength of linkage disequilibrium (LD) between markers and causal mutations. With Lewontin's measure of LD (known as D′), high levels of LD that extend over several million base pairs have been reported in livestock. However, this measure of LD can be strongly biased upward by small samples and by low allele frequencies. The aim of this study was to characterize the level and extent of LD in Holstein cattle in North America (Canada and the United States for purposes of this study) by using the squared correlation of the alleles at 2 loci (r²). The Affymetrix MegAllele GeneChip Bovine Mapping 10K single nucleotide polymorphism (SNP) array was used to genotype 821 bulls, from which 497 were used in the analysis of the extent of LD. A total of 5,564 SNP were used after filtering out SNP with more than 5% of Mendelian inconsistencies, with more than 20% missing genotypes, or with a minor allele frequency of less than 10%. Analysis of syntenic pairs revealed that useful LD (measured as r² > 0.3) occurred at distances shorter than 100 kb. Linkage disequilibrium decayed very rapidly, within a few hundred kilobase pairs. In addition, no substantial LD between unlinked loci was found. Using a sliding window analysis, we observed an irregular pattern of LD across the genome. These findings suggest that to capture useful LD, which is required for whole-genome fine mapping and genomic selection, a denser SNP map would be needed.     

Preliminary investigation on reliability of genomic estimated breeding values in the Danish Holstein population

This study investigated the reliability of genomic estimated breeding values (GEBV) in the Danish Holstein population. The data in the analysis included 3,330 bulls with both published conventional EBV and single nucleotide polymorphism (SNP) markers. After data editing, 38,134 SNP markers were available. In the analysis, all SNP were fitted simultaneously as random effects in a Bayesian variable selection model, which allows heterogeneous variances for different SNP markers. The response variables were the official EBV. Direct GEBV were calculated as the sum of individual SNP effects. Initial analyses of 4 index traits were carried out to compare models with different intensities of shrinkage for SNP effects; that is, mixture prior distributions of scaling factors (standard deviation of SNP effects) assuming 5, 10, 20, or 50% of SNP having large effects and the others having very small or no effects, and a single prior distribution common for all SNP. It was found that, in general, the model with a common prior distribution of scaling factors had better predictive ability than any mixture prior models. Therefore, a common prior model was used to estimate SNP effects and breeding values for all 18 index traits. Reliability of GEBV was assessed by squared correlation between GEBV and conventional EBV (r²_{GEBV, EBV}), and expected reliability was obtained from prediction error variance using a 5-fold cross validation. Squared correlations between GEBV and published EBV (without any adjustment) ranged from 0.252 to 0.700, with an average of 0.418. Expected reliabilities ranged from 0.494 to 0.733, with an average of 0.546. Averaged over 18 traits, r²_{GEBV, EBV} was 0.13 higher and expected reliability was 0.26 higher than reliability of conventional parent average. The results indicate that genomic selection can greatly improve the accuracy of preselection for young bulls compared with traditional selection based on parent average information.     

Single-step genome-wide association for longitudinal traits of Canadian Ayrshire,Holstein, and Jersey dairy cattle

Estimating single nucleotide polymorphism (SNP) effects over time is essential to identify and validate candidate genes (or quantitative trait loci) associated with time-dependent variation of economically important traits and to better understand the underlying mechanisms of lactation biology. Therefore, in this study, we aimed to estimate time-dependent effects of SNP and identifying candidate genes associated with milk (MY), fat (FY), and protein (PY) yields, and somatic cell score (SCS) in the first 3 lactations of Canadian Ayrshire, Holstein, and Jersey breeds, as well as suggest their potential pattern of phenotypic effect over time. Random regression coefficients for the additive direct genetic effect were estimated for each animal using single-step genomic BLUP, based on 2 random regression models: one considering MY, FY, and PY in the first 3 lactations and the other considering SCS in the first 3 lactations. Thereafter, SNP solutions were obtained for random regression coefficients, which were used to estimate the SNP effects over time (from 5 to 305 d in lactation). The top 1% of SNP that showed a high magnitude of SNP effect in at least 1 d in lactation were selected as relevant SNP for further analyses of candidate genes, and clustered according to the trajectory of their SNP effects over time. The majority of SNP selected for MY, FY, and PY increased the magnitude of their effects over time, for all breeds. In contrast, for SCS, most selected SNP decreased the magnitude of their effects over time, especially for the Holstein and Jersey breeds. In general, we identified a different set of candidate genes for each breed, and similar genes were found across different lactations for the same trait in the same breed. For some of the candidate genes, the suggested pattern of phenotypic effect changed among lactations. Among the lactations, candidate genes (and their suggested phenotypic effect over time) identified for the second and third lactations were more similar to each other than for the first lactation. Well-known candidate genes with major effects on milk production traits presented different suggested patterns of phenotypic effect across breeds, traits, and lactations in which they were identified. The candidate genes identified in this study can be used as target genes in studies of gene expression.     

Association of polymorphisms at DGAT1, leptin, SCD1, CAPN1 and CAST genes with color,marbling and water holding capacity in meat from beef cattle populations in Sweden

The objective of this study was to investigate the associations of single nucleotide polymorphisms (SNPs) at five candidate genes with meat pH, color, marbling and water holding capacity (WHC) in young bulls from five beef breeds (n = 243) in Sweden. The UASMS2 polymorphism at the leptin gene and the SNPs at the Stearoyl-CoA desaturase 1 gene (SCD1.878) and μ-calpain gene (CAPN1:c.947) were associated with variation in meat color traits after 6 days of exposure to air. The K232A polymorphism at the diacylglycerol O-acyltransferase 1 (DGAT1) gene and the CAPN1:c.947 SNP were associated with level of beef marbling. There was no association between the SNP at the calpastatin gene (CAST:c.155) and meat quality traits, nor was there any association of the tested SNPs with WHC traits and pH value.