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K A Weigel - One of the best experts on this subject based on the ideXlab platform.
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short communication genetic evaluation of stillbirth in us brown swiss and Jersey Cattle
Journal of Dairy Science, 2014Co-Authors: C Yao, K A Weigel, J B ColeAbstract:Stillbirth (SB) often results in reduced milk yield, compromised reproductive performance, and decreased dam longevity. Corrective mating can be used as a short-term solution to the problem, but long-term improvement of the population requires the routine calculation of genetic evaluations. Breeding values for SB have been available for Holstein (HO) bulls since 2006, but not for Brown Swiss (BS) or Jersey (JE) bulls. In this study, a multi-breed sire-maternal grandsire threshold model was used to perform genetic evaluations for SB of BS, JE, and HO bulls using more than 14 million purebred and crossbred calving records. Phenotypically, the percentage of SB (%SB) across all lactations were 3.7% in JE, 5.1% in BS, and 6.3% in HO. Direct heritabilities for BS, JE, and HO were 0.008, 0.007, and 0.008, and maternal heritabilities were 0.002, 0.016, and 0.021, respectively. Compared with HO, crossbred calvings from BS and JE bulls bred to HO cows lowered %SB by 1.5 and 1.2%, respectively. In general, %SB increased considerably as calving difficulty increased in all 3 breeds; however, in JE, %SB was constant for dystocia scores of 3 (needed assistance), 4 (considerable force), and 5 (extreme difficulty). Compared with purebred HO calvings, purebred BS and JE calvings had lower phenotypic %SB by up to 5.5 and 7.8%, respectively, and BS × HO and JE × HO crossbred calvings decreased %SB by up to 3.8 and 4.1%, respectively. As expected, SB rates in primiparous cows were higher than those in multiparous cows. Female calves had greater %SB than male calves in all parities for JE and in second-and-later parities for BS. Favorable (decreasing) phenotypic and genetic trends from 1999 to 2009 were observed in all 3 breeds. Heterosis of SB for BS and JE was −0.026 and −0.149, respectively, on the underlying scale, which corresponds to effects on service-sire SB (SSB) and daughter SB (DSB) predicted transmitting ability (PTA) of −0.3 and −0.5% in BS, and −1.5 and −2.7% in JE. Overall, in the current population, BS bulls had the most desirable average SSB PTA of 4.8%, compared with 5.6% for JE and 5.5% for HO. Brown Swiss and JE bulls both had average DSB PTA of 6.5%, lower than that of 7.7% in HO. Average reliabilities of SSB and DSB in 3 breeds ranged from 45 to 50%. The use of a BS-JE-HO multibreed genetic evaluation for SB in the United States is feasible, and the addition of SSB and DSB to the lifetime net merit selection index will help improve the profitability of BS and JE Cattle in the United States.
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accuracy of direct genomic values derived from imputed single nucleotide polymorphism genotypes in Jersey Cattle
Journal of Dairy Science, 2010Co-Authors: K A Weigel, G De Los Campos, Ana I Vazquez, Guilherme J M Rosa, Daniel Gianola, C P Van TassellAbstract:The objective of the present study was to evaluate the predictive ability of direct genomic values for economically important dairy traits when genotypes at some single nucleotide polymorphism (SNP) loci were imputed rather than measured directly. Genotypic data consisted of 42,552 SNP genotypes for each of 1,762 Jersey sires. Phenotypic data consisted of predicted transmitting abilities (PTA) for milk yield, protein percentage, and daughter pregnancy rate from May 2006 for 1,446 sires in the training set and from April 2009 for 316 sires in the testing set. The SNP effects were estimated using the Bayesian least absolute selection and shrinkage operator (LASSO) method with data of sires in the training set, and direct genomic values (DGV) for sires in the testing set were computed by multiplying these estimates by corresponding genotype dosages for sires in the testing set. The mean correlation across traits between DGV (before progeny testing) and PTA (after progeny testing) for sires in the testing set was 70.6% when all 42,552 SNP genotypes were used. When genotypes for 93.1, 96.6, 98.3, or 99.1% of loci were masked and subsequently imputed in the testing set, mean correlations across traits between DGV and PTA were 68.5, 64.8, 54.8, or 43.5%, respectively. When genotypes were also masked and imputed for a random 50% of sires in the training set, mean correlations across traits between DGV and PTA were 65.7, 63.2, 53.9, or 49.5%, respectively. Results of this study indicate that if a suitable reference population with high-density genotypes is available, a low-density chip comprising 3,000 equally spaced SNP may provide approximately 95% of the predictive ability observed with the BovineSNP50 Beadchip (Illumina Inc., San Diego, CA) in Jersey Cattle. However, if fewer than 1,500 SNP are genotyped, the accuracy of DGV may be limited by errors in the imputed genotypes of selection candidates.
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prediction of unobserved single nucleotide polymorphism genotypes of Jersey Cattle using reference panels and population based imputation algorithms
Journal of Dairy Science, 2010Co-Authors: K A Weigel, P M Vanraden, C P Van Tassell, Jeffrey R Oconnell, G.r. WiggansAbstract:The availability of dense single nucleotide polymorphism (SNP) genotypes for dairy Cattle has created exciting research opportunities and revolutionized practical breeding programs. Broader application of this technology will lead to situations in which genotypes from different low-, medium-, or high-density platforms must be combined. In this case, missing SNP genotypes can be imputed using family- or population-based algorithms. Our objective was to evaluate the accuracy of imputation in Jersey Cattle, using reference panels comprising 2,542 animals with 43,385 SNP genotypes and study samples of 604 animals for which genotypes were available for 1, 2, 5, 10, 20, 40, or 80% of loci. Two population-based algorithms, fastPHASE 1.2 (P. Scheet and M. Stevens; University of Washington TechTransfer Digital Ventures Program, Seattle, WA) and IMPUTE 2.0 (B. Howie and J. Marchini; Department of Statistics, University of Oxford, UK), were used to impute genotypes on Bos taurus autosomes 1, 15, and 28. The mean proportion of genotypes imputed correctly ranged from 0.659 to 0.801 when 1 to 2% of genotypes were available in the study samples, from 0.733 to 0.964 when 5 to 20% of genotypes were available, and from 0.896 to 0.995 when 40 to 80% of genotypes were available. In the absence of pedigrees or genotypes of close relatives, the accuracy of imputation may be modest (generally 40,000 SNP) from a reference population. Accurate imputation of high-density genotypes from inexpensive low- or medium-density platforms could greatly enhance the efficiency of whole-genome selection programs in dairy Cattle.
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assessment of the impact of somatic cell count on functional longevity in holstein and Jersey Cattle using survival analysis methodology
Journal of Dairy Science, 2005Co-Authors: D Z Caraviello, G E Shook, K A Weigel, P L RueggAbstract:Survival analysis in a Weibull proportional hazards model was used to evaluate the impact of somatic cell count (SCC) on the involuntary culling rate of US Holstein and Jersey cows with first calvings from 1990 to 2000. The full data set, consisting of records from 978,043 Holstein and 250,835 Jersey cows, was divided into subsets (5 for Holsteins and 3 for Jerseys) based on herd average lactation SCC values. Functional longevity (also known as herd life or length of productive life) was defined as days from first calving until culling or censoring, after correcting for milk production. Our model included the time-dependent effects of herd-year-season, parity by stage of lactation interaction, within-herd-year quintile ranking for mature equivalent production, and lactation average SCC (rounded to the nearest 50,000 cells/mL), as well as the time-independent effect of age at first calving. Parameters of the Weibull distribution, as well as variance components for herd-year-season effects, were estimated within each group of herds. Mean failure and censoring times decreased as herd average SCC increased, and a nonlinear relationship was observed between SCC and longevity in all groups. The risk of culling for Holstein cows with lactation average SCC > 700,000 cells/mL was 3.4, 2.7, or 2.3 times greater, respectively, than that of Holstein cows with SCC of 200,000 to 250,000 cells/mL in herds with low, medium, or high average SCC. Likewise, the risk of culling for Jersey cows with lactation average SCC > 700,000 cells/mL was 4.0, 2.9, or 2.2 times greater, respectively, than that of Jersey cows with SCC of 200,000 to 250,000 cells/mL in low, medium, or high SCC herds. These trends may reflect more stringent culling of high SCC cows in herds with few mastitis problems. In addition, cows with lactation average SCC <100,000 cells/mL had a slightly higher risk of culling than cows with SCC of 100,000 to 200,000 cells/mL in both breeds, particularly in herds with high average SCC, where exposure to mastitis pathogens was likely.
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analysis of the relationship between type traits inbreeding and functional survival in Jersey Cattle using a weibull proportional hazards model
Journal of Dairy Science, 2003Co-Authors: D Z Caraviello, K A Weigel, Daniel GianolaAbstract:A Weibull proportional hazards model was used to analyze the effects of 13 linear type traits, final score, and inbreeding on the functional survival of 268,008 US Jersey cows in 2416 herds with first calving from 1981 to 2000. Functional survival was defined as the number of days from first calving until involuntary culling or censoring. The statistical model included the time-dependent effects of herd-year-season of calving, parity by stage of lactation interaction, and within-herd-year quintile for mature equivalent milk yield, as well as the time-independent effects of inbreeding, age at first calving, and linear type traits or final score (analyzed one at a time). Each type trait was divided into 10 classes, and the relative risk of involuntary culling was calculated for animals in each class after accounting for the aforementioned management factors. Type traits with the greatest contribution to the likelihood function were udder depth, fore udder attachment, front teat placement, and udder support. Cows with low scores for these traits had a risk of culling that was 1.3 to 1.8 times that of cows with intermediate scores. Cows with high scores for udder depth and udder support had a risk of culling only 0.7 to 0.85 as great as that of cows with intermediate scores. Intermediate scores were desirable for rear leg set, dairy form, and strength, but stature, rump angle, and rump width had negligible effects on survival. Cows with low final scores had a risk of culling that was 1.35 times that of cows with intermediate scores, whereas cows with high final scores had a risk of culling that was 0.8 times that of cows with intermediate scores. Animals with inbreeding coefficients greater than 10% had a slightly higher risk of culling than animals with inbreeding coefficients less than 5%.
B W Kirkpatrick - One of the best experts on this subject based on the ideXlab platform.
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short communication heritability estimates for susceptibility to mycobacterium avium subspecies paratuberculosis infection defined by elisa and fecal culture test results in Jersey Cattle
Journal of Dairy Science, 2014Co-Authors: Yalda Zare, G E Shook, Michael Collins, B W KirkpatrickAbstract:Abstract Paratuberculosis (Johne's disease), an enteric disorder in ruminants caused by Mycobacterium avium ssp. paratuberculosis , causes economic losses in excess of $200 million annually to the US dairy industry. Costly diagnostic testing, cumbersome control programs, incurability, and ineffective vaccination all make M. avium ssp. paratuberculosis susceptibility a good candidate for genetic studies and genetic selection a potentially useful adjunct to management-based control programs. No report has been published for heritability of susceptibility to M. avium ssp. paratuberculosis infection in Jersey Cattle. The objective of this study was to estimate variance components and heritability for susceptibility to M. avium ssp. paratuberculosis infection in US Jersey Cattle. Data consisted of complete serum ELISA and partial fecal culture results on a total of 2,861 Jersey cows from 23 commercial herds throughout the United States after editing. Four M. avium ssp. paratuberculosis susceptibility phenotypes were defined using (1) ELISA sample-to-positive ratios as a continuous trait, (2) ELISA results as a binary trait (positive=1, negative=0), (3) ELISA results as an ordered categorical trait, and (4) a combined test in which ELISA and fecal culture results were both taken into account in a binary analysis. Three statistical models, including linear, binary threshold, and ordered threshold sire models, were used to analyze the data. All analyses were executed using the restricted maximum likelihood method in ASReml 3 software. The heritability estimates were low to moderate and ranged from 0.08 (±0.03) to 0.27 (±0.11) based on different trait definitions. The nonzero heritability indicates that susceptibility to M. avium ssp. paratuberculosis infection in Jersey Cattle is influenced by genetic factors. Therefore, selection of the least susceptible animals could decrease genetic predisposition to M. avium ssp. paratuberculosis infection in Jersey populations in future generations.
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genome wide association analysis and genomic prediction of mycobacterium avium subspecies paratuberculosis infection in us Jersey Cattle
PLOS ONE, 2014Co-Authors: Yalda Zare, G E Shook, Michael Collins, B W KirkpatrickAbstract:Paratuberculosis (Johne’s disease), an enteric disorder in ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), causes economic losses in excess of $200 million annually to the US dairy industry. To identify genomic regions underlying susceptibility to MAP infection in Jersey Cattle, a case-control genome-wide association study (GWAS) was performed. Blood and fecal samples were collected from ∼5,000 mature cows in 30 commercial Jersey herds from across the US. Discovery data consisted of 450 cases and 439 controls genotyped with the Illumina BovineSNP50 BeadChip. Cases were animals with positive ELISA and fecal culture (FC) results. Controls were animals negative to both ELISA and FC tests that matched cases on birth date and herd. Validation data consisted of 180 animals including 90 cases (positive to FC) and 90 controls (negative to ELISA and FC), selected from discovery herds and genotyped by Illumina BovineLD BeadChip (∼7K SNPs). Two analytical approaches were used: single-marker GWAS using the GRAMMAR-GC method and Bayesian variable selection (Bayes C) using GenSel software. GRAMMAR-GC identified one SNP on BTA7 at 68 megabases (Mb) surpassing a significance threshold of 5×10−5. ARS-BFGL-NGS-11887 on BTA23 (27.7 Mb) accounted for the highest percentage of genetic variance (3.3%) in the Bayes C analysis. SNPs identified in common by GRAMMAR-GC and Bayes C in both discovery and combined data were mapped to BTA23 (27, 29 and 44 Mb), 3 (100, 101, 106 and 107 Mb) and 17 (57 Mb). Correspondence between results of GRAMMAR-GC and Bayes C was high (70–80% of most significant SNPs in common). These SNPs could potentially be associated with causal variants underlying susceptibility to MAP infection in Jersey Cattle. Predictive performance of the model developed by Bayes C for prediction of infection status of animals in validation set was low (55% probability of correct ranking of paired case and control samples).
G E Shook - One of the best experts on this subject based on the ideXlab platform.
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short communication heritability estimates for susceptibility to mycobacterium avium subspecies paratuberculosis infection defined by elisa and fecal culture test results in Jersey Cattle
Journal of Dairy Science, 2014Co-Authors: Yalda Zare, G E Shook, Michael Collins, B W KirkpatrickAbstract:Abstract Paratuberculosis (Johne's disease), an enteric disorder in ruminants caused by Mycobacterium avium ssp. paratuberculosis , causes economic losses in excess of $200 million annually to the US dairy industry. Costly diagnostic testing, cumbersome control programs, incurability, and ineffective vaccination all make M. avium ssp. paratuberculosis susceptibility a good candidate for genetic studies and genetic selection a potentially useful adjunct to management-based control programs. No report has been published for heritability of susceptibility to M. avium ssp. paratuberculosis infection in Jersey Cattle. The objective of this study was to estimate variance components and heritability for susceptibility to M. avium ssp. paratuberculosis infection in US Jersey Cattle. Data consisted of complete serum ELISA and partial fecal culture results on a total of 2,861 Jersey cows from 23 commercial herds throughout the United States after editing. Four M. avium ssp. paratuberculosis susceptibility phenotypes were defined using (1) ELISA sample-to-positive ratios as a continuous trait, (2) ELISA results as a binary trait (positive=1, negative=0), (3) ELISA results as an ordered categorical trait, and (4) a combined test in which ELISA and fecal culture results were both taken into account in a binary analysis. Three statistical models, including linear, binary threshold, and ordered threshold sire models, were used to analyze the data. All analyses were executed using the restricted maximum likelihood method in ASReml 3 software. The heritability estimates were low to moderate and ranged from 0.08 (±0.03) to 0.27 (±0.11) based on different trait definitions. The nonzero heritability indicates that susceptibility to M. avium ssp. paratuberculosis infection in Jersey Cattle is influenced by genetic factors. Therefore, selection of the least susceptible animals could decrease genetic predisposition to M. avium ssp. paratuberculosis infection in Jersey populations in future generations.
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genome wide association analysis and genomic prediction of mycobacterium avium subspecies paratuberculosis infection in us Jersey Cattle
PLOS ONE, 2014Co-Authors: Yalda Zare, G E Shook, Michael Collins, B W KirkpatrickAbstract:Paratuberculosis (Johne’s disease), an enteric disorder in ruminants caused by Mycobacterium avium subspecies paratuberculosis (MAP), causes economic losses in excess of $200 million annually to the US dairy industry. To identify genomic regions underlying susceptibility to MAP infection in Jersey Cattle, a case-control genome-wide association study (GWAS) was performed. Blood and fecal samples were collected from ∼5,000 mature cows in 30 commercial Jersey herds from across the US. Discovery data consisted of 450 cases and 439 controls genotyped with the Illumina BovineSNP50 BeadChip. Cases were animals with positive ELISA and fecal culture (FC) results. Controls were animals negative to both ELISA and FC tests that matched cases on birth date and herd. Validation data consisted of 180 animals including 90 cases (positive to FC) and 90 controls (negative to ELISA and FC), selected from discovery herds and genotyped by Illumina BovineLD BeadChip (∼7K SNPs). Two analytical approaches were used: single-marker GWAS using the GRAMMAR-GC method and Bayesian variable selection (Bayes C) using GenSel software. GRAMMAR-GC identified one SNP on BTA7 at 68 megabases (Mb) surpassing a significance threshold of 5×10−5. ARS-BFGL-NGS-11887 on BTA23 (27.7 Mb) accounted for the highest percentage of genetic variance (3.3%) in the Bayes C analysis. SNPs identified in common by GRAMMAR-GC and Bayes C in both discovery and combined data were mapped to BTA23 (27, 29 and 44 Mb), 3 (100, 101, 106 and 107 Mb) and 17 (57 Mb). Correspondence between results of GRAMMAR-GC and Bayes C was high (70–80% of most significant SNPs in common). These SNPs could potentially be associated with causal variants underlying susceptibility to MAP infection in Jersey Cattle. Predictive performance of the model developed by Bayes C for prediction of infection status of animals in validation set was low (55% probability of correct ranking of paired case and control samples).
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assessment of the impact of somatic cell count on functional longevity in holstein and Jersey Cattle using survival analysis methodology
Journal of Dairy Science, 2005Co-Authors: D Z Caraviello, G E Shook, K A Weigel, P L RueggAbstract:Survival analysis in a Weibull proportional hazards model was used to evaluate the impact of somatic cell count (SCC) on the involuntary culling rate of US Holstein and Jersey cows with first calvings from 1990 to 2000. The full data set, consisting of records from 978,043 Holstein and 250,835 Jersey cows, was divided into subsets (5 for Holsteins and 3 for Jerseys) based on herd average lactation SCC values. Functional longevity (also known as herd life or length of productive life) was defined as days from first calving until culling or censoring, after correcting for milk production. Our model included the time-dependent effects of herd-year-season, parity by stage of lactation interaction, within-herd-year quintile ranking for mature equivalent production, and lactation average SCC (rounded to the nearest 50,000 cells/mL), as well as the time-independent effect of age at first calving. Parameters of the Weibull distribution, as well as variance components for herd-year-season effects, were estimated within each group of herds. Mean failure and censoring times decreased as herd average SCC increased, and a nonlinear relationship was observed between SCC and longevity in all groups. The risk of culling for Holstein cows with lactation average SCC > 700,000 cells/mL was 3.4, 2.7, or 2.3 times greater, respectively, than that of Holstein cows with SCC of 200,000 to 250,000 cells/mL in herds with low, medium, or high average SCC. Likewise, the risk of culling for Jersey cows with lactation average SCC > 700,000 cells/mL was 4.0, 2.9, or 2.2 times greater, respectively, than that of Jersey cows with SCC of 200,000 to 250,000 cells/mL in low, medium, or high SCC herds. These trends may reflect more stringent culling of high SCC cows in herds with few mastitis problems. In addition, cows with lactation average SCC <100,000 cells/mL had a slightly higher risk of culling than cows with SCC of 100,000 to 200,000 cells/mL in both breeds, particularly in herds with high average SCC, where exposure to mastitis pathogens was likely.
Goutam Sahana - One of the best experts on this subject based on the ideXlab platform.
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Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey Cattle
Journal of Dairy Science, 2020Co-Authors: Md Mesbah-uddin, Bernt Guldbrandtsen, Mogens Lund, Goutam SahanaAbstract:Haplotypes that are common in a population but not observed as homotypes in living animals may harbor lethal alleles that compromise embryo survival. In this study, we searched for homozygous-deficient haplotypes in the genomes of 19,309 Nordic Red Dairy (RDC) and 4,291 Danish Jersey (JER) Cattle genotyped using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). For statistically significant deficient haplotypes, we evaluated the effect on nonreturn rate in at-risk matings (mating between carrier bull and daughter of carrier sire) versus not-at-risk matings (mating between noncarrier bull and daughter of noncarrier sire). Next, we analyzed whole-genome sequence variants from the 1000 Bull Genomes Project to identify putative causal variants underlying these haplotypes. In RDC, we identified 3 homozygous-deficient regions (HDR) that overlapped with known recessive lethal mutations: a 662-kb deletion on chromosome 12 in RDC [Online Mendelian Inheritance in Animals (OMIA) 001901-9913), a missense mutation in TUBD1, g.11063520T>C, in Braunvieh Cattle (OMIA 0019399913), and a 525-kb deletion on chromosome 23 in RDC (OMIA 001991-9913)]. In addition, we identified 15 novel HDR and their tag haplotypes for the underlying causative variants. The tag haplotype located between 39.2 and 40.3 Mbp on chromosome 18 had a negative effect on nonreturn rate in at-risk mating, confirming embryonic lethality. In Danish Jersey, we identified 12 novel HDR and their tag haplotypes for underlying causative variants. For 3 of these 12 tag haplotypes, insemination records of at-risk mating showed a negative effect on nonreturn rate, confirming the association with early embryonic mortality. Cattle that had both genotype and whole-genome sequence data were analyzed to detect the causative variants underlying each tag haplotype. However, none of the functional variants or deletions showed concordance with carrier status of the novel tag haplotypes. Carrier status of these detected haplotypes can be used to select bulls to reduce the frequencies of lethal alleles in the population and to avoid at-risk matings.
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genetic dissection of milk yield traits and mastitis resistance quantitative trait loci on chromosome 20 in dairy Cattle
Journal of Dairy Science, 2015Co-Authors: Naveen Kumar Kadri, Bernt Guldbrandtsen, Mogens Sando Lund, Goutam SahanaAbstract:Intense selection to increase milk yield has had negative consequences for mastitis incidence in dairy Cattle. Due to low heritability of mastitis resistance and an unfavorable genetic correlation with milk yield, a reduction in mastitis through traditional breeding has been difficult to achieve. Here, we examined quantitative trait loci (QTL) that segregate for clinical mastitis and milk yield on Bos taurus autosome 20 (BTA20) to determine whether both traits are affected by a single polymorphism (pleiotropy) or by multiple closely linked polymorphisms. In the latter but not the former situation, undesirable genetic correlation could potentially be broken by selecting animals that have favorable variants for both traits. First, we performed a within-breed association study using a haplotype-based method in Danish Holstein Cattle (HOL). Next, we analyzed Nordic Red dairy Cattle (RDC) and Danish Jersey Cattle (JER) with the goal of determining whether these QTL identified in Holsteins were segregating across breeds. Genotypes for 12,566 animals (5,966 HOL, 5,458 RDC, and 1,142 JER) were determined by using the Illumina Bovine SNP50 BeadChip (50K; Illumina, San Diego, CA), which identifies 1,568 single nucleotide polymorphisms on BTA20. Data were combined, phased, and clustered into haplotype states, followed by within- and across-breed haplotype-based association analyses using a linear mixed model. Association signals for both clinical mastitis and milk yield peaked in the 26- to 40-Mb region on BTA20 in HOL. Single-variant association analyses were carried out in the QTL region using whole sequence level variants imputed from references of 2,036 HD genotypes (BovineHD BeadChip; Illumina) and 242 whole-genome sequences. The milk QTL were also segregating in RDC and JER on the BTA20-targeted region; however, an indication of differences in the causal factor(s) was observed across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone receptor gene showed strong association with milk, fat, and protein yields. In HOL, the highest peaks for milk yield and susceptibility to mastitis were separated by over 3.5 Mb (3.8 Mb by haplotype analysis, 3.6 Mb by single nucleotide polymorphism analysis), suggesting separate genetic variants for the traits. Further analysis yielded 2 candidate mutations for the mastitis QTL, at 33,642,072 bp (rs378947583) in an intronic region of the caspase recruitment domain protein 6 gene and 35,969,994 bp (rs133596506) in an intronic region of the leukemia-inhibitory factor receptor gene. These findings suggest that it may be possible to separate these beneficial and detrimental genetic factors through targeted selective breeding.
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genome wide association study using high density single nucleotide polymorphism arrays and whole genome sequences for clinical mastitis traits in dairy Cattle1
Journal of Dairy Science, 2014Co-Authors: Goutam Sahana, Bernt Guldbrandtsen, Bo Thomsen, Larserik Holm, Frank Panitz, R F Brondum, Christian Bendixen, M S LundAbstract:Mastitis is a mammary disease that frequently affects dairy Cattle. Despite considerable research on the development of effective prevention and treatment strategies, mastitis continues to be a significant issue in bovine veterinary medicine. To identify major genes that affect mastitis in dairy Cattle, 6 chromosomal regions on Bos taurus autosome (BTA) 6, 13, 16, 19, and 20 were selected from a genome scan for 9 mastitis phenotypes using imputed high-density single nucleotide polymorphism arrays. Association analyses using sequence-level variants for the 6 targeted regions were carried out to map causal variants using whole-genome sequence data from 3 breeds. The quantitative trait loci (QTL) discovery population comprised 4,992 progeny-tested Holstein bulls, and QTL were confirmed in 4,442 Nordic Red and 1,126 Jersey Cattle. The targeted regions were imputed to the sequence level. The highest association signal for clinical mastitis was observed on BTA 6 at 88.97 Mb in Holstein Cattle and was confirmed in Nordic Red Cattle. The peak association region on BTA 6 contained 2 genes: vitamin D-binding protein precursor (GC) and neuropeptide FF receptor 2 (NPFFR2), which, based on known biological functions, are good candidates for affecting mastitis. However, strong linkage disequilibrium in this region prevented conclusive determination of the causal gene. A different QTL on BTA 6 located at 88.32 Mb in Holstein Cattle affected mastitis. In addition, QTL on BTA 13 and 19 were confirmed to segregate in Nordic Red Cattle and QTL on BTA 16 and 20 were confirmed in Jersey Cattle. Although several candidate genes were identified in these targeted regions, it was not possible to identify a gene or polymorphism as the causal factor for any of these regions.
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a genome wide association study for milk production traits in danish Jersey Cattle using a 50k single nucleotide polymorphism chip
Journal of Animal Science, 2010Co-Authors: M D Mai, Goutam Sahana, F B Christiansen, Bernt GuldbrandtsenAbstract:Quantitative trait loci for milk production traits in Danish Jersey Cattle were mapped by a genome-wide association analysis using a mixed model. The analysis incorporated 1,039 bulls and 33,090 SNP and resulted in 98 detected combinations of QTL and traits on 27 BTA. These QTL comprised 30 for milk index, 50 for fat index, and 18 for protein index. The evidence presents 33 genome-wide QTL on 14 BTA. Of these, 7 had effects on milk index, 21 on fat index, and 5 on protein index. Among the genome-wide QTL, 26 have been previously reported, 2 on BTA4 and BTA5 were new for milk index, and 5 on BTA4, BTA5, BTA13, BTA20, and BTA29 were new QTL for fat index. We found 7 pleiotropic or very closely linked QTL. Most of the QTL were associated with polymorphisms within narrow regions and several may represent the effects of polymorphisms of genes: DGAT1, casein, ARFGAP3, CYP11B1, and CDC-like kinase 4. By a chromosome-wide threshold, 65 additional QTL were detected. Many of them are likely to represent QTL. The results are interesting from a breeding perspective and contribute to the search for the genes causing the polymorphisms important for milk production traits.
Bernt Guldbrandtsen - One of the best experts on this subject based on the ideXlab platform.
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Novel haplotypes responsible for prenatal death in Nordic Red and Danish Jersey Cattle
Journal of Dairy Science, 2020Co-Authors: Md Mesbah-uddin, Bernt Guldbrandtsen, Mogens Lund, Goutam SahanaAbstract:Haplotypes that are common in a population but not observed as homotypes in living animals may harbor lethal alleles that compromise embryo survival. In this study, we searched for homozygous-deficient haplotypes in the genomes of 19,309 Nordic Red Dairy (RDC) and 4,291 Danish Jersey (JER) Cattle genotyped using the Illumina BovineSNP50 BeadChip (Illumina Inc., San Diego, CA). For statistically significant deficient haplotypes, we evaluated the effect on nonreturn rate in at-risk matings (mating between carrier bull and daughter of carrier sire) versus not-at-risk matings (mating between noncarrier bull and daughter of noncarrier sire). Next, we analyzed whole-genome sequence variants from the 1000 Bull Genomes Project to identify putative causal variants underlying these haplotypes. In RDC, we identified 3 homozygous-deficient regions (HDR) that overlapped with known recessive lethal mutations: a 662-kb deletion on chromosome 12 in RDC [Online Mendelian Inheritance in Animals (OMIA) 001901-9913), a missense mutation in TUBD1, g.11063520T>C, in Braunvieh Cattle (OMIA 0019399913), and a 525-kb deletion on chromosome 23 in RDC (OMIA 001991-9913)]. In addition, we identified 15 novel HDR and their tag haplotypes for the underlying causative variants. The tag haplotype located between 39.2 and 40.3 Mbp on chromosome 18 had a negative effect on nonreturn rate in at-risk mating, confirming embryonic lethality. In Danish Jersey, we identified 12 novel HDR and their tag haplotypes for underlying causative variants. For 3 of these 12 tag haplotypes, insemination records of at-risk mating showed a negative effect on nonreturn rate, confirming the association with early embryonic mortality. Cattle that had both genotype and whole-genome sequence data were analyzed to detect the causative variants underlying each tag haplotype. However, none of the functional variants or deletions showed concordance with carrier status of the novel tag haplotypes. Carrier status of these detected haplotypes can be used to select bulls to reduce the frequencies of lethal alleles in the population and to avoid at-risk matings.
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genetic dissection of milk yield traits and mastitis resistance quantitative trait loci on chromosome 20 in dairy Cattle
Journal of Dairy Science, 2015Co-Authors: Naveen Kumar Kadri, Bernt Guldbrandtsen, Mogens Sando Lund, Goutam SahanaAbstract:Intense selection to increase milk yield has had negative consequences for mastitis incidence in dairy Cattle. Due to low heritability of mastitis resistance and an unfavorable genetic correlation with milk yield, a reduction in mastitis through traditional breeding has been difficult to achieve. Here, we examined quantitative trait loci (QTL) that segregate for clinical mastitis and milk yield on Bos taurus autosome 20 (BTA20) to determine whether both traits are affected by a single polymorphism (pleiotropy) or by multiple closely linked polymorphisms. In the latter but not the former situation, undesirable genetic correlation could potentially be broken by selecting animals that have favorable variants for both traits. First, we performed a within-breed association study using a haplotype-based method in Danish Holstein Cattle (HOL). Next, we analyzed Nordic Red dairy Cattle (RDC) and Danish Jersey Cattle (JER) with the goal of determining whether these QTL identified in Holsteins were segregating across breeds. Genotypes for 12,566 animals (5,966 HOL, 5,458 RDC, and 1,142 JER) were determined by using the Illumina Bovine SNP50 BeadChip (50K; Illumina, San Diego, CA), which identifies 1,568 single nucleotide polymorphisms on BTA20. Data were combined, phased, and clustered into haplotype states, followed by within- and across-breed haplotype-based association analyses using a linear mixed model. Association signals for both clinical mastitis and milk yield peaked in the 26- to 40-Mb region on BTA20 in HOL. Single-variant association analyses were carried out in the QTL region using whole sequence level variants imputed from references of 2,036 HD genotypes (BovineHD BeadChip; Illumina) and 242 whole-genome sequences. The milk QTL were also segregating in RDC and JER on the BTA20-targeted region; however, an indication of differences in the causal factor(s) was observed across breeds. A previously reported F279Y mutation (rs385640152) within the growth hormone receptor gene showed strong association with milk, fat, and protein yields. In HOL, the highest peaks for milk yield and susceptibility to mastitis were separated by over 3.5 Mb (3.8 Mb by haplotype analysis, 3.6 Mb by single nucleotide polymorphism analysis), suggesting separate genetic variants for the traits. Further analysis yielded 2 candidate mutations for the mastitis QTL, at 33,642,072 bp (rs378947583) in an intronic region of the caspase recruitment domain protein 6 gene and 35,969,994 bp (rs133596506) in an intronic region of the leukemia-inhibitory factor receptor gene. These findings suggest that it may be possible to separate these beneficial and detrimental genetic factors through targeted selective breeding.
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genome wide association study using high density single nucleotide polymorphism arrays and whole genome sequences for clinical mastitis traits in dairy Cattle1
Journal of Dairy Science, 2014Co-Authors: Goutam Sahana, Bernt Guldbrandtsen, Bo Thomsen, Larserik Holm, Frank Panitz, R F Brondum, Christian Bendixen, M S LundAbstract:Mastitis is a mammary disease that frequently affects dairy Cattle. Despite considerable research on the development of effective prevention and treatment strategies, mastitis continues to be a significant issue in bovine veterinary medicine. To identify major genes that affect mastitis in dairy Cattle, 6 chromosomal regions on Bos taurus autosome (BTA) 6, 13, 16, 19, and 20 were selected from a genome scan for 9 mastitis phenotypes using imputed high-density single nucleotide polymorphism arrays. Association analyses using sequence-level variants for the 6 targeted regions were carried out to map causal variants using whole-genome sequence data from 3 breeds. The quantitative trait loci (QTL) discovery population comprised 4,992 progeny-tested Holstein bulls, and QTL were confirmed in 4,442 Nordic Red and 1,126 Jersey Cattle. The targeted regions were imputed to the sequence level. The highest association signal for clinical mastitis was observed on BTA 6 at 88.97 Mb in Holstein Cattle and was confirmed in Nordic Red Cattle. The peak association region on BTA 6 contained 2 genes: vitamin D-binding protein precursor (GC) and neuropeptide FF receptor 2 (NPFFR2), which, based on known biological functions, are good candidates for affecting mastitis. However, strong linkage disequilibrium in this region prevented conclusive determination of the causal gene. A different QTL on BTA 6 located at 88.32 Mb in Holstein Cattle affected mastitis. In addition, QTL on BTA 13 and 19 were confirmed to segregate in Nordic Red Cattle and QTL on BTA 16 and 20 were confirmed in Jersey Cattle. Although several candidate genes were identified in these targeted regions, it was not possible to identify a gene or polymorphism as the causal factor for any of these regions.
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genomic selection strategies in a small dairy Cattle population evaluated for genetic gain and profit
Journal of Dairy Science, 2014Co-Authors: Jorn Rind Thomasen, C Eggerdanner, Alfons Willam, Bernt Guldbrandtsen, M S Lund, A C SorensenAbstract:Abstract The objective of this study was to evaluate a genomic breeding scheme in a small dairy Cattle population that was intermediate in terms of using both young bulls (YB) and progeny-tested bulls (PB). This scheme was compared with a conventional progeny testing program without use of genomic information and, as the extreme case, a juvenile scheme with genomic information, where all bulls were used before progeny information was available. The population structure, cost, and breeding plan parameters were chosen to reflect the Danish Jersey Cattle population, being representative for a small dairy Cattle population. The population consisted of 68,000 registered cows. Annually, 1,500 bull dams were screened to produce the 500 genotyped bull calves from which 60 YB were selected to be progeny tested. Two unfavorably correlated traits were included in the breeding goal, a production trait ( h 2 =0.30) and a functional trait ( h 2 =0.04). An increase in reliability of 5 percentage points for each trait was used in the default genomic scenario. A deterministic approach was used to model the different breeding programs, where the primary evaluation criterion was annual monetary genetic gain (AMGG). Discounted profit was used as an indicator of the economic outcome. We investigated the effect of varying the following parameters: (1) increase in reliability due to genomic information, (2) number of genotyped bull calves, (3) proportion of bull dam sires that are young bulls, and (4) proportion of cow sires that are young bulls. The genomic breeding scheme was both genetically and economically superior to the conventional breeding scheme, even in a small dairy Cattle population where genomic information causes a relatively low increase in reliability of breeding values. Assuming low reliabilities of genomic predictions, the optimal breeding scheme according to AMGG was characterized by mixed use of YB and PB as bull sires. Exclusive use of YB for production cows increased AMGG up to 3 percentage points. The results from this study supported our hypothesis that strong interaction effects exist. The strongest interaction effects were obtained between increased reliabilities of genomic estimated breeding values and more intensive use of YB. The juvenile scheme was genetically inferior when the increase in reliability was low (5 percentage points), but became genetically superior at higher reliabilities of genomic estimated breeding values. The juvenile scheme was always superior according to discounted profit because of the shorter generation interval and minimizing costs for housing and feeding waiting bulls.
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a genome wide association study for milk production traits in danish Jersey Cattle using a 50k single nucleotide polymorphism chip
Journal of Animal Science, 2010Co-Authors: M D Mai, Goutam Sahana, F B Christiansen, Bernt GuldbrandtsenAbstract:Quantitative trait loci for milk production traits in Danish Jersey Cattle were mapped by a genome-wide association analysis using a mixed model. The analysis incorporated 1,039 bulls and 33,090 SNP and resulted in 98 detected combinations of QTL and traits on 27 BTA. These QTL comprised 30 for milk index, 50 for fat index, and 18 for protein index. The evidence presents 33 genome-wide QTL on 14 BTA. Of these, 7 had effects on milk index, 21 on fat index, and 5 on protein index. Among the genome-wide QTL, 26 have been previously reported, 2 on BTA4 and BTA5 were new for milk index, and 5 on BTA4, BTA5, BTA13, BTA20, and BTA29 were new QTL for fat index. We found 7 pleiotropic or very closely linked QTL. Most of the QTL were associated with polymorphisms within narrow regions and several may represent the effects of polymorphisms of genes: DGAT1, casein, ARFGAP3, CYP11B1, and CDC-like kinase 4. By a chromosome-wide threshold, 65 additional QTL were detected. Many of them are likely to represent QTL. The results are interesting from a breeding perspective and contribute to the search for the genes causing the polymorphisms important for milk production traits.