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Sun C.,National Association of Animal Breeders | VanRaden P.M.,U.S. Department of Agriculture | O'Connell J.R.,University of Maryland, Baltimore | Weigel K.A.,University of Wisconsin - Madison | Gianola D.,University of Wisconsin - Madison
Journal of Dairy Science | Year: 2013

Computerized mating programs using genomic information are needed by breed associations, artificial-insemination organizations, and on-farm software providers, but such software is already challenged by the size of the relationship matrix. As of October 2012, over 230,000 Holsteins obtained genomic predictions in North America. Efficient methods of storing, computing, and transferring genomic relationships from a central database to customers via a web query were developed for approximately 165,000 genotyped cows and the subset of 1,518 bulls whose semen was available for purchase at that time. This study, utilizing 3 breeds, investigated differences in sire selection, methods of assigning mates, the use of genomic or pedigree relationships, and the effect of including dominance effects in a mating program. For both Jerseys and Holsteins, selection and mating programs were tested using the top 50 marketed bulls for genomic and traditional lifetime net merit as well as 50 randomly selected bulls. The 500 youngest genotyped cows in the largest herd in each breed were assigned mates of the same breed with limits of 10 cows per bull and 1 bull per cow (only 79 cows and 8 bulls for Brown Swiss). A dominance variance of 4.1 and 3.7% was estimated for Holsteins and Jerseys using 45,187 markers and management group deviation for milk yield. Sire selection was identified as the most important component of improving expected progeny value, followed by managing inbreeding and then inclusion of dominance. The respective percentage gains for milk yield in this study were 64, 27, and 9, for Holsteins and 73, 20, and 7 for Jerseys. The linear programming method of assigning a mate outperformed sequential selection by reducing genomic or pedigree inbreeding by 0.86 to 1.06 and 0.93 to 1.41, respectively. Use of genomic over pedigree relationship information provided a larger decrease in expected progeny inbreeding and thus greater expected progeny value. Based on lifetime net merit, the economic value of using genomic relationships was >$3 million per year for Holsteins when applied to all genotyped females, assuming that each will provide 1 replacement. Previous mating programs required transferring only a pedigree file to customers, but better service is possible by incorporating genomic relationships, more precise mate allocation, and dominance effects. Economic benefits will continue to grow as more females are genotyped. © 2013 American Dairy Science Association.

Sun C.,National Association of Animal Breeders | VanRaden P.M.,U.S. Department of Agriculture
PLoS ONE | Year: 2014

Long-term response of genomic selection can be improved by considering allele frequencies of selected markers or quantitative trait loci (QTLs). A previous formula to weight allele frequency of favorable minor alleles was tested, and 2 new formulas were developed. The previous formula used nonlinear weights based on square root of frequency of the favorable allele. The new formulas included a parameter δ to balance long- and short-term progress; one used square root and the other used simple linear weights. The formulas were tested by simulation of 20 generations (population size of 3,000 for each generation) with direct selection on 3,000 QTLs (100 per chromosome). A QTL distribution with normally distributed allele effects and a heavy-tailed distribution were tested. Optimum δ from simulation was applied to data from Holstein, Jersey and Brown Swiss dairy cattle to compare differences of adjusted and official genomic evaluations. From simulation, optimum δ was 0.4 for the heavy-tailed QTL distribution but only 0.1 or 0.2 for a normal distribution. The previous formula had slower response than unweighted selection in early generations and did not recover by generation 20. Long-term response was slightly greater with the new formulas than with unweighted selection; the linear formula may be best for routine use because of more progress in early generations compared to nonlinear formula. Official and adjusted U.S. evaluations based on actual genotypes and estimated marker effects were correlated by 0.994 for Holsteins and Jerseys and 0.989 for Brown Swiss using linear weighting of allele frequency, which was higher than nonlinear weighting. The difference between adjusted and official evaluations was highly correlated negatively with an animal's average genomic relationship to the population. Thus, strategies to reduce genomic inbreeding may achieve almost as much long-term progress as selection of favorable minor alleles.

VanRaden P.M.,U.S. Department of Agriculture | Olson K.M.,National Association of Animal Breeders | Null D.J.,U.S. Department of Agriculture | Hutchison J.L.,U.S. Department of Agriculture
Journal of Dairy Science | Year: 2011

Five new recessive defects were discovered in Holsteins, Jerseys, and Brown Swiss by examining haplotypes that had a high population frequency but were never homozygous. The method required genotypes only from apparently normal individuals and not from affected embryos. Genotypes from the BovineSNP50 BeadChip (Illumina, San Diego, CA) were examined for 58,453 Holsteins, 5,288 Jerseys, and 1,991 Brown Swiss with genotypes in the North American database. Haplotypes with a length of ≤75 markers were obtained. Eleven candidate haplotypes were identified, with the earliest carrier born before 1980; 7 to 90 homozygous haplotypes were expected, but none were observed in the genomic data. Expected numbers were calculated using either the actual mating pattern or assuming random mating. Probability of observing no homozygotes ranged from 0.0002 for 7 to 10 -45 for 90 expected homozygotes. Phenotypic effects were confirmed for 5 of the 11 candidate haplotypes using 14,911,387 Holstein, 830,391 Jersey, and 68,443 Brown Swiss records for conception rate. Estimated effect for interaction of carrier service sire with carrier maternal grandsire ranged from -3.0 to -3.7 percentage points, which was slightly smaller than the -3.9 to -4.6 percentage points expected for lethal recessives but slightly larger than estimated effects for previously known lethal alleles of -2.5 percentage points for brachyspina and -2.9 percentage points for complex vertebral malformation. Conception rate was coded as a success only if the gestation went to term or the cow was confirmed to be pregnant. Estimated effect of carrier interaction for stillbirth rate based on 10,876,597 Holstein and 25,456 Jersey records was small. Thus, lethal effects may include conception, gestation, and stillbirth losses. Carrier frequency has been >20% for many years for the confirmed defect in Jerseys and is currently 16% for the defect in Brown Swiss. The 3 defects discovered in Holsteins have carrier frequencies of 2.7 to 6.4% in the current population. For previously known defects, map locations and lack of homozygotes were consistent with the literature and lethal recessive inheritance, but numbers of expected homozygotes for some were small because of low frequency. Very large genotypic and phenotypic data sets allow efficient detection of smaller and less frequent effects. Haplotype tests can help breeders avoid carrier matings for such defects and reduce future frequencies. © 2011 American Dairy Science Association.

Sun C.,National Association of Animal Breeders | VanRaden P.M.,U.S. Department of Agriculture | Cole J.B.,U.S. Department of Agriculture | O'Connell J.R.,University of Maryland Baltimore County
PLoS ONE | Year: 2014

Dominance may be an important source of non-additive genetic variance for many traits of dairy cattle. However, nearly all prediction models for dairy cattle have included only additive effects because of the limited number of cows with both genotypes and phenotypes. The role of dominance in the Holstein and Jersey breeds was investigated for eight traits: milk, fat, and protein yields; productive life; daughter pregnancy rate; somatic cell score; fat percent and protein percent. Additive and dominance variance components were estimated and then used to estimate additive and dominance effects of single nucleotide polymorphisms (SNPs). The predictive abilities of three models with both additive and dominance effects and a model with additive effects only were assessed using ten-fold cross-validation. One procedure estimated dominance values, and another estimated dominance deviations; calculation of the dominance relationship matrix was different for the two methods. The third approach enlarged the dataset by including cows with genotype probabilities derived using genotyped ancestors. For yield traits, dominance variance accounted for 5 and 7% of total variance for Holsteins and Jerseys, respectively; using dominance deviations resulted in smaller dominance and larger additive variance estimates. For nonyield traits, dominance variances were very small for both breeds. For yield traits, including additive and dominance effects fit the data better than including only additive effects; average correlations between estimated genetic effects and phenotypes showed that prediction accuracy increased when both effects rather than just additive effects were included. No corresponding gains in prediction ability were found for non-yield traits. Including cows with derived genotype probabilities from genotyped ancestors did not improve prediction accuracy. The largest additive effects were located on chromosome 14 near DGAT1 for yield traits for both breeds; those SNPs also showed the largest dominance effects for fat yield (both breeds) as well as for Holstein milk yield.

Wiggans G.R.,U.S. Department of Agriculture | Cooper T.A.,U.S. Department of Agriculture | VanRaden P.M.,U.S. Department of Agriculture | Olson K.M.,National Association of Animal Breeders | Tooker M.E.,U.S. Department of Agriculture
Journal of Dairy Science | Year: 2012

Genomic evaluations using genotypes from the Illumina Bovine3K BeadChip (3K) became available in September 2010 and were made official in December 2010. The majority of 3K-genotyped animals have been Holstein females. Approximately 5% of male 3K genotypes and between 3.7 and 13.9%, depending on registry status, of female genotypes had sire conflicts. The chemistry used for the 3K is different from that of the Illumina BovineSNP50 BeadChip (50K) and causes greater variability in the accuracy of the genotypes. Approximately 2% of genotypes were rejected due to this inaccuracy. A single nucleotide polymorphism (SNP) was determined to be not usable for genomic evaluation based on percentage missing, percentage of parent-progeny conflicts, and Hardy-Weinberg equilibrium discrepancies. Those edits left 2,683 of the 2,900 3K SNP for use in genomic evaluations. The mean minor allele frequencies (MAF) for Holstein, Jersey, and Brown Swiss were 0.32, 0.28, and 0.29, respectively. Eighty-one SNP had both a large number of missing genotypes and a large number of parent-progeny conflicts, suggesting a correlation between call rate and accuracy. To calculate a genomic predicted transmitting ability (GPTA) the genotype of an animal tested on a 3K is imputed to the 45,187 SNP included in the current genomic evaluation based on the 50K. The accuracy of imputation increases as the number of genotyped parents increases from none to 1 to both. The average percentage of imputed genotypes that matched the corresponding actual 50K genotypes was 96.3%. The correlation of a GPTA calculated from a 3K genotype that had been imputed to 50K and GPTA from its actual 50K genotype averaged 0.959 across traits for Holsteins and was slightly higher for Jerseys at 0.963. The average difference in GPTA from the 50K- and 3K-based genotypes across trait was close to 0. The evaluation system has been modified to accommodate the characteristics of the 3K. The low cost of the 3K has greatly increased genotyping of females. Prior to the availability of the 3K (August 2010), female genotyping accounted for 38.7% of the genotyped animals. In the past year, the portion of total genotypes from females across all chip types rose to 59.0%. © 2012 American Dairy Science Association.

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