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A genome scan for homozygous haplotype deficiency coupled with whole-genome sequence data analysis is a very effective method to identify embryonic lethal mutations in cattle. Among other factors, the power of the approach depends on the availability of a greater amount of genotyping and sequencing data. In the present study, we analyzed the largest known panel of Illumina BovineSNP50 (Illumina Inc., San Diego, CA) genotypes, comprising 401,896 Holstein animals, and we report the mapping of a new embryonic lethal haplotype on chromosome 27, called HH7. We fine mapped the locus in a 2.0-Mb interval using an identical-by-descent approach and analyzed genome sequence data from 4 carrier and 143 noncarrier Holstein bulls to identify the causative mutation. We detected a strong candidate variant in the gene encoding centromere protein U (CENPU), a centromere component essential for proper chromosome segregation during mitosis. The mutant allele is a deletion of 4 nucleotides located at position +3 to +6 bp after the splicing donor site of exon 11. Cross-species nucleotide alignment revealed that the nucleotide at position +3 is entirely conserved among vertebrates, suggesting that it plays an important role in the regulation of CENPU splicing. For verification, we genotyped the candidate variant in 232,775 Holstein individuals and did not observe any homozygotes, whereas 16 were expected (Poisson P -value = 1.1 × 10−7; allele frequency = 0.8%). In addition, genotyping of 250,602 animals from 19 additional breeds revealed that the mutant allele is restricted to animals of Holstein descent. Finally, we estimated the effect of the candidate variant on 2 fertility traits in at-risk mating (i.e., between carrier bulls and daughters of carrier bulls) versus non-risk mating. In agreement with a recessive lethal inheritance pattern, we observed a marked reduction in both conception rate and 56-d nonreturn rate in heifers and cows. The effect on 56-d nonreturn rate suggests that a substantial proportion of homozygous mutants die before 35 d after insemination, which is consistent with the early embryonic death previously reported in CENPU−/− mouse embryos. In conclusion, we demonstrate that with more than 400,000 genotypes, we can map very rare recessive lethal mutations segregating at a frequency below 1% in the population. We recommend performing new analyses regularly as data are accumulating. [ABSTRACT FROM AUTHOR]

Single-breed genomic selection (GS) based on medium single nucleotide polymorphism (SNP) density (~50,000; 50K) is now routinely implemented in several large cattle breeds. However, building large enough reference populations remains a challenge for many medium or small breeds. The high-density BovineHD BeadChip (HD chip; Illumina Inc., San Diego, CA) containing 777,609 SNP developed in 2010 is characterized by short-distance linkage disequilibrium expected to be maintained across breeds. Therefore, combining reference populations can be envisioned. A population of 1,869 influential ancestors from 3 dairy breeds (Holstein, Montbéliarde, and Normande) was genotyped with the HD chip. Using this sample, 50K genotypes were imputed within breed to high-density genotypes, leading to a large HD reference population. This population was used to develop a multi-breed genomic evaluation. The goal of this paper was to investigate the gain of multi-breed genomic evaluation for a small breed. The advantage of using a large breed (Normande in the present study) to mimic a small breed is the large potential validation population to compare alternative genomic selection approaches more reliably. In the Normande breed, 3 training sets were defined with 1,597, 404, and 198 bulls, and a unique validation set included the 394 youngest bulls. For each training set, estimated breeding values (EBV) were computed using pedigree-based BLUP, single-breed BayesC, or multi-breed BayesC for which the reference population was formed by any of the Normande training data sets and 4,989 Holstein and 1,788 Montbéliarde bulls. Phenotypes were standardized by within-breed genetic standard deviation, the proportion of polygenic variance was set to 30%, and the estimated number of SNP with a nonzero effect was about 7,000. The 2 genomic selection (GS) approaches were performed using either the 50K or HD genotypes. The correlations between EBV and observed daughter yield deviations (DYD) were computed for 6 traits and using the different prediction approaches. Compared with pedigree-based BLUP, the average gain in accuracy with GS in small populations was 0.057 for the single-breed and 0.086 for multi-breed approach. This gain was up to 0.193 and 0.209, respectively, with the large reference population. Improvement of EBV prediction due to the multi-breed evaluation was higher for animals not closely related to the reference population. In the case of a breed with a small reference population size, the increase in correlation due to multi-breed GS was 0.141 for bulls without their sire in reference population compared with 0.016 for bulls with their sire in reference population. These results demonstrate that multi-breed GS can contribute to increase genomic evaluation accuracy in small breeds. [ABSTRACT FROM AUTHOR]

The list of standard abbreviations for JDS is available at adsa.org/jds-abbreviations-24. Nonstandard abbreviations are available in the Notes. The performance of an adult dairy cow may be influenced by events that occur before her birth. The present study investigated the potential effects of 2 prenatal groups of factors, assisted reproductive technologies and maternal characteristics (e.g., dam parity), on offspring performance during their first lactation in populations of 2 dairy cow breeds: French Holstein and Montbéliarde. The different assisted reproductive technologies studied included the type of semen (conventional or X-sorted) used for AI and the technology of conception used (AI, embryo transfer, or in vitro fertilization). Three maternal characteristics were considered: (1) the dam age at first calving, (2) dam parity number, and (3) indicators of dam udder health during gestation (SCS and events of clinical mastitis). First, we investigated whether heifer survival from 3 d to 18 mo old was associated with any of the prenatal factors considered. We then estimated the associations of these prenatal factors with 8 traits of commercial interest: (1) stature, (2–4) milk, fat, and protein yields, (5) SCS, (6) clinical mastitis, and (7–8) heifer and cow conception rate, all measured on genotyped cows. Linear models were used for this study with the prenatal factors as covariates in the model, and for the 8 traits, phenotypes were adjusted for their corresponding genomic EBV. The results indicated that the survival rate of heifers born from embryo transfer was significantly higher than that of heifers born from AI (probably due to preferential management practices), and the other prenatal factors did not explain large differences in heifer survival. Among the Montbéliarde cows born from AI, those born from X-sorted semen showed a lightly but significantly lower milk yield than those born without X-sorting of the semen (−52 kg of milk in the first lactation). Among the Holstein cows, those born from embryo transfer presented significantly lower milk performance than cows born from AI. Regarding the maternal characteristics, none or very weak associations were found between the dam age at first calving and the offspring performance in both breeds. Dam parity, on the other hand, was associated with offspring performance for milk, fat, and protein yield in both breeds, but not in the same direction. In the Holstein breed, an increase in dam parity was favorable for offspring performance for milk, fat, and protein yield, whereas in the Montbéliarde breed, an increase in dam parity was associated with lower milk and protein yield and no association was found for fat yield. The udder health of the dam during gestation was not or only weakly associated with the traits studied in the offspring. Although some significant associations were identified due to the large sample size, the effects were modest, typically less than 1% of the phenotypic mean, and were not consistently observed across the 2 breeds. [ABSTRACT FROM AUTHOR]