Adenylate kinase 9 is essential for sperm function and male fertility in mammals.

Despite passing routine laboratory tests for semen quality, bulls used in artificial insemination exhibit significant variation in fertility. Routine analysis of fertility data identified a dairy bull with extreme subfertility (10% pregnancy rate). To characterize the subfertility phenotype, a range of in vitro, in vivo, and molecular assays were carried out. Sperm from the subfertile bull exhibited reduced motility and severely reduced caffeine-induced hyperactivation compared to controls. Ability to penetrate the zona pellucida, cleavage rate, cleavage kinetics, and blastocyst yield after IVF or AI were significantly lower than in control bulls. Whole-genome sequencing from semen and RNA sequencing of testis tissue revealed a critical mutation in adenylate kinase 9 (AK9) that impaired splicing, leading to a premature termination codon and a severely truncated protein. Mice deficient in AK9 were generated to further investigate the function of the gene; knockout males were phenotypically indistinguishable from their wild-type littermates but produced immotile sperm that were incapable of normal fertilization. These sperm exhibited numerous abnormalities, including a low ATP concentration and reduced motility. RNA-seq analysis of their testis revealed differential gene expression of components of the axoneme and sperm flagellum as well as steroid metabolic processes. Sperm ultrastructural analysis showed a high percentage of sperm with abnormal flagella. Combined bovine and murine data indicate the essential metabolic role of AK9 in sperm motility and/or hyperactivation, which in turn affects sperm binding and penetration of the zona pellucida. Thus, AK9 has been found to be directly implicated in impaired male fertility in mammals.

Herd solutions from genetic evaluations can be used as a tool to rescale the expected expression of genetic potential in cattle.

The objective of this study was to determine whether response to selection for carcass weight (CW), conformation (CC) and fat (CF), and the association between heterosis and carcass performance varied by herd environment in cattle. Following edits, carcass information was available for 4,616,761 cattle, of which the majority were some crossbred combination of the following breeds: Angus, Aubrac, Belgian Blue, Blonde d'Aquitaine, Charolais, Hereford, Holstein-Friesian, Jersey, Limousin, Saler, Shorthorn and Simmental. Herd environment was defined separately for each carcass trait using herd solutions outputted from carcass trait genetic evaluations. A total of 3,859 herds were stratified, for each trait, into one of five strata based on their corresponding percentile herd solution rank, with the response to selection and the effect of heterosis then estimated within each stratum. The response in CW and CC from selection on the respective estimated breeding values (EBV) increased between the lowest (0.71 kg and 0.89 CC score increase per unit increase in the respective EBV) and highest (0.99 kg and 1.25 CC score increase per unit increase in the respective EBV) corresponding herd stratum. The response in CF from selection on CF EBV, however, reduced between the lowest and highest CF herd stratum (respective increases of 0.93 and 0.83 CF scores per unit increase in CF EBV). In addition, the effect of a unit increase in heterosis coefficient on CW, CC and CF also varied by herd stratum. Furthermore, results (i.e. the area under relative operating characteristic curves) from the present study demonstrated that the response to selection and heterosis effects estimated for the different herd stratum can be used, along with EBVs and the herd solutions themselves, to improve the accuracy of phenotypic predictions. Results from the present study could help producers to make more informed breeding decisions that are bespoke to their herd.

Genomic regions associated with muscularity in beef cattle differ in five contrasting cattle breeds.

BACKGROUND: Linear type traits, which reflect the muscular characteristics of an animal, could provide insight into how, in some cases, morphologically very different animals can yield the same carcass weight. Such variability may contribute to differences in the overall value of the carcass since primal cuts vary greatly in price; such variability may also hinder successful genome-based association studies. Therefore, the objective of our study was to identify genomic regions that are associated with five muscularity linear type traits and to determine if these significant regions are common across five different breeds. Analyses were carried out using linear mixed models on imputed whole-genome sequence data in each of the five breeds, separately. Then, the results of the within-breed analyses were used to conduct an across-breed meta-analysis per trait. RESULTS: We identified many quantitative trait loci (QTL) that are located across the whole genome and associated with each trait in each breed. The only commonality among the breeds and traits was a large-effect pleiotropic QTL on BTA2 that contained the MSTN gene, which was associated with all traits in the Charolais and Limousin breeds. Other plausible candidate genes were identified for muscularity traits including PDE1A, PPP1R1C and multiple collagen and HOXD genes. In addition, associated (gene ontology) GO terms and KEGG pathways tended to differ between breeds and between traits especially in the numerically smaller populations of Angus, Hereford, and Simmental breeds. Most of the SNPs that were associated with any of the traits were intergenic or intronic SNPs located within regulatory regions of the genome. CONCLUSIONS: The commonality between the Charolais and Limousin breeds indicates that the genetic architecture of the muscularity traits may be similar in these breeds due to their similar origins. Conversely, there were vast differences in the QTL associated with muscularity in Angus, Hereford, and Simmental. Knowledge of these differences in genetic architecture between breeds is useful to develop accurate genomic prediction equations that can operate effectively across breeds. Overall, the associated QTL differed according to trait, which suggests that breeding for a morphologically different (e.g. longer and wider versus shorter and smaller) more efficient animal may become possible in the future.

Genome-wide association study of endo-parasite phenotypes using imputed whole-genome sequence data in dairy and beef cattle.

BACKGROUND: Quantitative genetic studies suggest the existence of variation at the genome level that affects the ability of cattle to resist to parasitic diseases. The objective of the current study was to identify regions of the bovine genome that are associated with resistance to endo-parasites. METHODS: Individual cattle records were available for Fasciola hepatica-damaged liver from 18 abattoirs. Deregressed estimated breeding values (EBV) for F. hepatica-damaged liver were generated for genotyped animals with a record for F. hepatica-damaged liver and for genotyped sires with a least one progeny record for F. hepatica-damaged liver; 3702 animals were available. In addition, individual cow records for antibody response to F. hepatica on 6388 genotyped dairy cows, antibody response to Ostertagia ostertagi on 8334 genotyped dairy cows and antibody response to Neospora caninum on 4597 genotyped dairy cows were adjusted for non-genetic effects. Genotypes were imputed to whole-sequence; after edits, 14,190,141 single nucleotide polymorphisms (SNPs) and 16,603,644 SNPs were available for cattle with deregressed EBV for F. hepatica-damaged liver and cows with an antibody response to a parasitic disease, respectively. Association analyses were undertaken using linear regression on one SNP at a time, in which a genomic relationship matrix accounted for the relationships between animals. RESULTS: Genomic regions for F. hepatica-damaged liver were located on Bos taurus autosomes (BTA) 1, 8, 11, 16, 17 and 18; each region included at least one SNP with a p value lower than 10-6. Five SNPs were identified as significant (q value < 0.05) for antibody response to N. caninum and were located on BTA21 or 25. For antibody response to F. hepatica and O. ostertagi, six and nine quantitative trait loci (QTL) regions that included at least one SNP with a p value lower than 10-6 were identified, respectively. Gene set enrichment analysis revealed a significant association between functional annotations related to the olfactory system and QTL that were suggestively associated with endo-parasite phenotypes. CONCLUSIONS: A number of novel genomic regions were suggestively associated with endo-parasite phenotypes across the bovine genome and two genomic regions on BTA21 and 25 were associated with antibody response to N. caninum.

Genome-wide association study for calving performance using high-density genotypes in dairy and beef cattle.

BACKGROUND: Calving difficulty and perinatal mortality are prevalent in modern-day cattle production systems. It is well-established that there is a genetic component to both traits, yet little is known about their underlying genomic architecture, particularly in beef breeds. Therefore, we performed a genome-wide association study using high-density genotypes to elucidate the genomic architecture of these traits and to identify regions of the bovine genome associated with them. RESULTS: Genomic regions associated with calving difficulty (direct and maternal) and perinatal mortality were detected using two statistical approaches: (1) single-SNP (single nucleotide polymorphism) regression and (2) a Bayesian approach. Data included high-density genotypes on 770 Holstein-Friesian, 927 Charolais and 963 Limousin bulls. Several novel or previously identified genomic regions were detected but associations differed by breed. For example, two genomic associations, one each on chromosomes 18 and 2 explained 2.49 % and 3.13 % of the genetic variance in direct calving difficulty in the Holstein-Friesian and Charolais populations, respectively. Imputed Holstein-Friesian sequence data was used to refine the genomic regions responsible for significant associations. Several candidate genes on chromosome 18 were identified and four highly significant missense variants were detected within three of these genes (SIGLEC12, CTU1, and ZNF615). Nevertheless, only CTU1 contained a missense variant with a putative impact on direct calving difficulty based on SIFT (0.06) and Polyphen (0.95) scores. Using imputed sequence data, we refined a genomic region on chromosome 4 associated with maternal calving difficulty in the Holstein-Friesian population and found the strongest association with an intronic variant in the PCLO gene. A meta-analysis was performed across the three breeds for each calving performance trait to identify common variants associated with these traits in the three breeds. Our results suggest that a portion of the genetic variation in calving performance is common to all three breeds. CONCLUSION: The genomic architecture of calving performance is complex and mainly influenced by many polymorphisms of small effect. We identified several associations of moderate effect size but the majority were breed-specific, indicating that breed-specific alleles exist for calving performance or that the linkage phase between genotyped allele and causal mutation varies between breeds.

Exploring definitions of daily enteric methane emission phenotypes for genetic evaluations using a population of indoor-fed multi-breed growing cattle with feed intake data.

Genetic selection has been identified as a promising approach for reducing enteric methane (CH4) emissions; a prerequisite for genetic evaluations; however, these are estimates of the necessary genetic parameters based on a population representative of where the genetic evaluations will be used. The objective of this study was, therefore, to derive genetic parameters for a series of definitions of CH4, carbon dioxide (CO2), and dry matter intake (DMI) as well as genetic correlations between CH4, CO2, and DMI in a bid to address the paucity of studies involving methane emissions measured in beef cattle using GreenFeed systems. Lastly, estimated breeding values (EBV) were generated for nine alternative definitions of CH4 using the derived genetic parameters; the EBV were validated against both phenotypic performance (adjusted for non-genetic effects) and the Legarra and Reverter method comparing EBV generated for a subset of the dataset compared to EBV generated from the entire dataset. Individual animal CH4 and CO2 records were available from a population of 1,508 multi-breed growing beef cattle using 10 GreenFeed Emission Monitoring systems. Nine trait definitions for CH4 and CO2 were derived: individual spot measures, the average of all spot measures within a 3-h, 6-h, 12-h, 1-d, 5-d, 10-d, and 15-d period and the average of all spot measures across the full test period (20 to 114 d on test). Heritability estimates from 1,155 animals, for CH4, increased as the length of the averaging period increased and ranged from 0.09 ±â€…0.03 for the individual spot measures trait to 0.43 ±â€…0.11 for the full test average trait; a similar trend existed for CO2 with the estimated heritability ranging from 0.17 ±â€…0.04 to 0.50 ±â€…0.11. Enteric CH4 was moderately to strongly genetically correlated with DMI with a genetic correlation of 0.72 ±â€…0.02 between the spot measures of CH4 and a 1-d average DMI. Correlations, adjusted for heritability, between the adjusted phenotype and (parental average) EBV ranged from 0.56 to 1.14 across CH4 definitions and the slope between the adjusted phenotype and EBV ranged from 0.92 to 1.16 (expectation = 1). Validation results from the Legarra and Reverter regression method revealed a level bias of between -0.81 and -0.45, a dispersion bias of between 0.93 and 1.17, and ratio accuracy (ratio of the partial evaluation accuracies on whole evaluation accuracies) from 0.28 to 0.38. While EBV validation results yielded no consensus, CH4 is a moderately heritable trait, and selection for reduced CH4 is achievable.

Livestock production is a significant contributor to greenhouse gas emissions. Animal breeding programs have been proposed as a sustainable mitigation strategy to reduce enteric methane emissions in livestock production. Before creating a genetic evaluation for enteric methane production, it is important to estimate how much inter-animal genetic variability contributes to the observed differences in enteric methane production. The purpose of this study was to explore multiple enteric methane phenotypes and estimate how much phenotypic variation was due to genetic differences among 1,508 growing cattle of multiple breeds and crosses; also of interest was the extent of similarity in the genetic control of enteric methane, carbon dioxide, and feed intake (i.e., the genetic correlation) and to determine if selection of animals on the estimated genetic merit for methane emissions of their parents would manifest itself in differences in actual methane produced by those animals. Between 9% and 43% of the inter-animal differences in daily enteric methane production were due to differences in the genetic composition of those animals; the genetic control influencing methane production was similar to that of feed intake (i.e., a strong genetic correlation between methane emissions and feed intake of up to 0.72).

Predicting carcass cut yields in cattle from digital images using artificial intelligence.

Deep Learning (DL) has proven to be a successful tool for many image classification problems but has yet to be applied to carcass images. The aim of this study was to train DL models to predict carcass cut yields and compare predictions to more standard machine learning (ML) methods. Three approaches were undertaken to predict the grouped carcass cut yields of Grilling cuts and Roasting cuts from a large dataset of 54,598 and 69,246 animals respectively. The approaches taken were (1) animal phenotypic data used as features for a range of ML algorithms, (2) carcass images used to train Convolutional Neural Networks, and (3) carcass dimensions measured directly from the carcass images, combined with the associated phenotypic data and used as feature data for ML algorithms. Results showed that DL models can be trained to predict carcass cuts yields but an approach that uses carcass dimensions in ML algorithms performs slightly better in absolute terms.

Detection of Genomic Imprinting for Carcass Traits in Cattle Using Imputed High-Density Genotype Data.

Genomic imprinting is an epigenetic phenomenon defined as the silencing of an allele, at least partially, at a given locus based on the sex of the transmitting parent. The objective of the present study was to detect the presence of SNP-phenotype imprinting associations for carcass weight (CW), carcass conformation (CC) and carcass fat (CF) in cattle. The data used comprised carcass data, along with imputed, high-density genotype data on 618,837 single nucleotide polymorphisms (SNPs) from 23,687 cattle; all animal genotypes were phased with respect to parent of origin. Based on the phased genotypes and a series of single-locus linear models, 24, 339, and 316 SNPs demonstrated imprinting associations with CW, CC, and CF, respectively. Regardless of the trait in question, no known imprinted gene was located within 0.5 Mb of the SNPs demonstrating imprinting associations in the present study. Since all imprinting associations detected herein were at novel loci, further investigation of these regions may be warranted. Nonetheless, knowledge of these associations might be useful for improving the accuracy of genomic evaluations for these traits, as well as mate allocations systems to exploit the effects of genomic imprinting.

Phenotypic relationship and repeatability of methane emissions and performance traits in beef cattle using a GreenFeed system.

Rumen methanogenesis results in the loss of 6% to 10% of gross energy intake in cattle and globally is the single most significant source of anthropogenic methane (CH4) emissions. The purpose of this study was to analyze greenhouse gas traits recorded in a commercial feedlot unit to gain an understanding into the relationships between greenhouse gas traits and production traits. Methane and carbon dioxide (CO2) data recorded via multiple GreenFeed Emission Monitoring (GEM), systems as well as feed intake, live weight, ultrasound scanning data, and slaughter data were available on 1,099 animals destined for beef production, of which 648 were steers, 361 were heifers, and 90 were bulls. Phenotypic relationships between GEM emission measurements with feed intake, weight traits, muscle ultrasound data, and carcass traits were estimated. Utilization of GEM systems, daily patterns of methane output, and repeatability of GEM system measurements across averaging periods were also assessed. Methane concentrations varied with visit number, duration, and time of day of visit to the GEM system. Mean CH4 and CO2 varied between sex, with mean CH4 of 256.1 g/day ± 64.23 for steers, 234.7 g/day ± 59.46 for heifers, and 156.9 g/day ± 55.98 for young bulls. A 10-d average period of GEM system measurements were required for steers and heifers to achieve a minimum repeatability of 0.60; however, higher levels of repeatability were observed in animals that attended the GEM system more frequently. In contrast, CO2 emissions reached repeatability estimates >0.6 for steers and heifers in all averaging periods greater than 2-d, suggesting that cattle have a moderately consistent CO2 emission pattern across time periods. Animals with heavier bodyweights were observed to have higher levels of CH4 (correlation = 0.30) and CO2 production (correlation = 0.61), and when assessing direct methane, higher levels of dry matter intake were associated with higher methane output (correlation = 0.31). Results suggest that reducing CH4 can have a negative impact on growth and body composition of cattle. Methane ratio traits, such as methane yield and intensity were also evaluated, and while easy to understand and compare across populations, ratio traits are undesirable in animal breeding, due to the unpredictable level of response. Methane adjusted for dry matter intake and liveweight (Residual CH4) should be considered as an alternative emission trait when selecting for reduced emissions within breeding goals.

Methane production from cattle digestion results in the loss of 6% to 10% of gross energy intake in cattle and globally is the single most significant source of anthropogenic methane (CH4) emissions. The purpose of this study was to analyze greenhouse gas traits recorded in a commercial feedlot unit to gain an understanding into the relationships between greenhouse gas traits and production traits of economic importance. Methane and carbon dioxide emissions recorded using Greenfeed systems were available on a total of 1,099 animals. In addition, performance indicators such as feed intake, live weight, ultrasound scanning data, and slaughter data were also available on all animals. Phenotypic repeatability of CH4 ranged from 0.13 to 0.74, with a CH4 repeatability of >0.6 achieved by both heifers and steers in 10-d measuring period. Due to the high repeatability of CH4 measures, an accurate portrayal of CH4 production can be observed from a 10-d measuring period when measures are averaged. Methane emission data were positively correlated with traits of economic importance. Phenotypically, animals with heavier body weights and greater feed intake had higher emissions.

The Association Between Genomic Heterozygosity and Carcass Merit in Cattle.

The objective of the present study was to quantify the association between both pedigree and genome-based measures of global heterozygosity and carcass traits, and to identify single nucleotide polymorphisms (SNPs) exhibiting non-additive associations with these traits. The carcass traits of interest were carcass weight (CW), carcass conformation (CC) and carcass fat (CF). To define the genome-based measures of heterozygosity, and to quantify the non-additive associations between SNPs and the carcass traits, imputed, high-density genotype data, comprising of 619,158 SNPs, from 27,213 cattle were used. The correlations between the pedigree-based heterosis coefficient and the three defined genomic measures of heterozygosity ranged from 0.18 to 0.76. The associations between the different measures of heterozygosity and the carcass traits were biologically small, with positive associations for CW and CC, and negative associations for CF. Furthermore, even after accounting for the pedigree-based heterosis coefficient of an animal, part of the remaining variability in some of the carcass traits could be captured by a genomic heterozygosity measure. This signifies that the inclusion of both a heterosis coefficient based on pedigree information and a genome-based measure of heterozygosity could be beneficial to limiting bias in predicting additive genetic merit. Finally, one SNP located on Bos taurus (BTA) chromosome number 5 demonstrated a non-additive association with CW. Furthermore, 182 SNPs (180 SNPs on BTA 2 and two SNPs on BTA 21) demonstrated a non-additive association with CC, while 231 SNPs located on BTA 2, 5, 11, 13, 14, 18, 19 and 21 demonstrated a non-additive association with CF. Results demonstrate that heterozygosity both at a global level and at the level of individual loci contribute little to the variability in carcass merit.

DNA sequence polymorphisms within the bovine guanine nucleotide-binding protein Gs subunit alpha (Gsα)-encoding (GNAS) genomic imprinting domain are associated with performance traits.

BACKGROUND: Genes which are epigenetically regulated via genomic imprinting can be potential targets for artificial selection during animal breeding. Indeed, imprinted loci have been shown to underlie some important quantitative traits in domestic mammals, most notably muscle mass and fat deposition. In this candidate gene study, we have identified novel associations between six validated single nucleotide polymorphisms (SNPs) spanning a 97.6 kb region within the bovine guanine nucleotide-binding protein Gs subunit alpha gene (GNAS) domain on bovine chromosome 13 and genetic merit for a range of performance traits in 848 progeny-tested Holstein-Friesian sires. The mammalian GNAS domain consists of a number of reciprocally-imprinted, alternatively-spliced genes which can play a major role in growth, development and disease in mice and humans. Based on the current annotation of the bovine GNAS domain, four of the SNPs analysed (rs43101491, rs43101493, rs43101485 and rs43101486) were located upstream of the GNAS gene, while one SNP (rs41694646) was located in the second intron of the GNAS gene. The final SNP (rs41694656) was located in the first exon of transcripts encoding the putative bovine neuroendocrine-specific protein NESP55, resulting in an aspartic acid-to-asparagine amino acid substitution at amino acid position 192. RESULTS: SNP genotype-phenotype association analyses indicate that the single intronic GNAS SNP (rs41694646) is associated (P ≤ 0.05) with a range of performance traits including milk yield, milk protein yield, the content of fat and protein in milk, culled cow carcass weight and progeny carcass conformation, measures of animal body size, direct calving difficulty (i.e. difficulty in calving due to the size of the calf) and gestation length. Association (P ≤ 0.01) with direct calving difficulty (i.e. due to calf size) and maternal calving difficulty (i.e. due to the maternal pelvic width size) was also observed at the rs43101491 SNP. Following adjustment for multiple-testing, significant association (q ≤ 0.05) remained between the rs41694646 SNP and four traits (animal stature, body depth, direct calving difficulty and milk yield) only. Notably, the single SNP in the bovine NESP55 gene (rs41694656) was associated (P ≤ 0.01) with somatic cell count--an often-cited indicator of resistance to mastitis and overall health status of the mammary system--and previous studies have demonstrated that the chromosomal region to where the GNAS domain maps underlies an important quantitative trait locus for this trait. This association, however, was not significant after adjustment for multiple testing. The three remaining SNPs assayed were not associated with any of the performance traits analysed in this study. Analysis of all pairwise linkage disequilibrium (r2) values suggests that most allele substitution effects for the assayed SNPs observed are independent. Finally, the polymorphic coding SNP in the putative bovine NESP55 gene was used to test the imprinting status of this gene across a range of foetal bovine tissues. CONCLUSIONS: Previous studies in other mammalian species have shown that DNA sequence variation within the imprinted GNAS gene cluster contributes to several physiological and metabolic disorders, including obesity in humans and mice. Similarly, the results presented here indicate an important role for the imprinted GNAS cluster in underlying complex performance traits in cattle such as animal growth, calving, fertility and health. These findings suggest that GNAS domain-associated polymorphisms may serve as important genetic markers for future livestock breeding programs and support previous studies that candidate imprinted loci may act as molecular targets for the genetic improvement of agricultural populations. In addition, we present new evidence that the bovine NESP55 gene is epigenetically regulated as a maternally expressed imprinted gene in placental and intestinal tissues from 8-10 week old bovine foetuses.

Single nucleotide polymorphisms within the bovine DLK1-DIO3 imprinted domain are associated with economically important production traits in cattle.

Previous studies show that DNA sequence variation within the mammalian DLK1-DIO3 imprinted domain influences production traits in domestic livestock, most notably the ovine callipyge phenotype. We assessed genotype-phenotype associations between 7 single nucleotide polymorphisms (SNPs) within the orthologous bovine DLK1-DIO3 domain and performance traits in 848 progeny-tested Holstein-Friesian dairy sires. One SNP (MEG3_01) located proximal to the maternally expressed 3 (MEG3/Gtl2) gene was associated with milk yield, subcutaneous fat levels, and progeny carcass conformation (P ≤ 0.01) and also tended to be associated with milk fat and protein yield (P ≤ 0.10). A single SNP (CLPG_01) within the putative CLPG1 locus was associated with progeny carcass fat (P ≤ 0.05), whereas a single SNP (PEG11_01) located proximal to the paternally expressed 11 (PEG11/Rtl) gene was associated with progeny carcass weight (P ≤ 0.05). The MEG3_01 SNP together with an additional 2 SNPs (MEG8_01 and MEG8_02) located proximal to the putative maternally expressed 8 (MEG8/Rian) ortholog were associated (P ≤ 0.05) with perinatal mortality. Finally, one SNP (MEG3_03) was associated (P ≤ 0.05) with gestation length, whereas both the CLPG_01 and MEG8_01 SNPs also tended to be associated with calving interval (P ≤ 0.10). Linkage disequilibrium analysis suggests that some phenotypic associations observed at these loci are independent. To our knowledge, this is one of the first studies demonstrating associations between the bovine DLK1-DIO3 domain and milk, carcass, fertility and, health traits in cattle. This imprinted domain may serve as a potential target for future genetic selection strategies.

Single nucleotide polymorphisms at the imprinted bovine insulin-like growth factor 2 (IGF2) locus are associated with dairy performance in Irish Holstein-Friesian cattle.

The imprinted insulin-like growth factor 2 gene (IGF2) encodes a fetal mitogenic hormone protein (IGF-II) and has previously been shown to be associated with performance in dairy cattle. In this study we assessed genotype-phenotype associations between four single nucleotide polymorphisms (SNPs) located within the bovine IGF2 locus on chromosome 29 and a range of performance traits related to milk production, animal growth and body size, fertility and progeny survival in 848 progeny-tested Irish Holstein-Friesian sires. Two of the four SNPs (rs42196909 and IGF2.g-3815A>G), which were in strong linkage disequilibrium (r2 = 0·995), were associated with milk yield (P ≤ 0·01) and milk protein yield (P ≤ 0·05); the rs42196901 SNP was also associated (P ≤ 0·05) with milk fat yield. Associations (P ≤ 0·05) with milk fat percentage and milk protein percentage were observed at the rs42196901 and IGF2.g-3815A>G SNPs, respectively. The rs42196909 and IGF2.g-3815A>G SNPs were also associated with progeny carcass conformation (P ≤ 0·05), while an association (P ≤ 0·01) with progeny carcass weight was observed at the rs42194733 SNP locus. None of the four SNPs were associated with body size, fertility and progeny survival. These findings support previous work which suggests that the IGF2 locus is an important biological regulator of milk production in dairy cattle and add to an accumulating body of research showing that imprinted genes influence many complex performance traits in cattle.

Contribution of herd characteristics to best linear unbiased estimates of slaughter traits in beef cattle.

Genetic evaluations separate phenotypes into their contributing additive genetic effects and non-(additive) genetic effects, with the former termed best linear unbiased predictions, and the latter termed best linear unbiased estimates (BLUEs). For the purpose of the present study, genetic evaluations, along with phenotypic data from 4 137 376 animals, were used to generate herd, year of slaughter and sex contemporary group BLUEs for various slaughter-related traits. These slaughter traits included carcass weight (CW), carcass conformation (CC) and carcass fat (CF). For the 4 665 herds that were consistently slaughtering ≥10 animals/year between the years 2014 and 2018, inclusive, all relevant contemporary group BLUEs were collapsed into a single herd-year value; results herein relate to these herds. The within-year herd-year BLUE correlations between CW and CC, between CW and CF, and between CC and CF were 0.51, 0.10 and -0.04, respectively. The repeatability across years of the herd-year BLUEs for CW, CC and CF was 0.66, 0.59 and 0.50, respectively. Furthermore, when the herds were stratified, within year, on the percentile rank of their herd-year BLUEs, herds had the greatest probability of remaining in the same BLUE stratum from one year to the next. In addition, results from the present study determined that various herd characteristics are associated with differences in the herd BLUEs. Results from the present study could be used to advise beef producers on the most promising strategy to improve the carcass merit of their animals.

Identification of genomic regions that exhibit sexual dimorphism for size and muscularity in cattle.

Sexual dimorphism, the phenomenon whereby males and females of the same species are distinctive in some aspect of appearance or size, has previously been documented in cattle for traits such as growth rate and carcass merit using a quantitative genetics approach. No previous study in cattle has attempted to document sexual dimorphism at a genome level; therefore, the objective of the present study was to determine whether genomic regions associated with size and muscularity in cattle exhibited signs of sexual dimorphism. Analyses were undertaken on 10 linear-type traits that describe the muscular and skeletal characteristics of both males and females of five beef cattle breeds: 1,444 Angus (AA), 6,433 Charolais (CH), 1,129 Hereford, 8,745 Limousin (LM), and 1,698 Simmental. Genome-wide association analyses were undertaken using imputed whole-genome sequence data for each sex separately by breed. For each single-nucleotide polymorphism (SNP) that was segregating in both sexes, the difference between the allele substitution effect sizes for each sex, in each breed separately, was calculated. Suggestively (P ≤ 1 × 10-5) sexually dimorphic SNPs that were segregating in both males and females were detected for all traits in all breeds, although the location of these SNPs differed by both trait and breed. Significantly (P ≤ 1 × 10-8) dimorphic SNPs were detected in just three traits in the AA, seven traits in the CH, and three traits in the LM. The vast majority of all segregating autosomal SNPs (86% in AA to 94% in LM) had the same minor allele in both males and females. Differences (P ≤ 0.05) in allele frequencies between the sexes were observed for between 36% (LM) and 66% (AA) of the total autosomal SNPs that were segregating in both sexes. Dimorphic SNPs were located within a number of genes related to muscularity and/or size including the NAB1, COL5A2, and IWS1 genes on BTA2 that are located close to, and thought to be co-inherited with, the MSTN gene. Overall, sexual dimorphism exists in cattle at the genome level, but it is not consistent by either trait or breed.

DNA sequence polymorphisms in a panel of eight candidate bovine imprinted genes and their association with performance traits in Irish Holstein-Friesian cattle.

BACKGROUND: Studies in mice and humans have shown that imprinted genes, whereby expression from one of the two parentally inherited alleles is attenuated or completely silenced, have a major effect on mammalian growth, metabolism and physiology. More recently, investigations in livestock species indicate that genes subject to this type of epigenetic regulation contribute to, or are associated with, several performance traits, most notably muscle mass and fat deposition. In the present study, a candidate gene approach was adopted to assess 17 validated single nucleotide polymorphisms (SNPs) and their association with a range of performance traits in 848 progeny-tested Irish Holstein-Friesian artificial insemination sires. These SNPs are located proximal to, or within, the bovine orthologs of eight genes (CALCR, GRB10, PEG3, PHLDA2, RASGRF1, TSPAN32, ZIM2 and ZNF215) that have been shown to be imprinted in cattle or in at least one other mammalian species (i.e. human/mouse/pig/sheep). RESULTS: Heterozygosities for all SNPs analysed ranged from 0.09 to 0.46 and significant deviations from Hardy-Weinberg proportions (P ≤ 0.01) were observed at four loci. Phenotypic associations (P ≤ 0.05) were observed between nine SNPs proximal to, or within, six of the eight analysed genes and a number of performance traits evaluated, including milk protein percentage, somatic cell count, culled cow and progeny carcass weight, angularity, body conditioning score, progeny carcass conformation, body depth, rump angle, rump width, animal stature, calving difficulty, gestation length and calf perinatal mortality. Notably, SNPs within the imprinted paternally expressed gene 3 (PEG3) gene cluster were associated (P ≤ 0.05) with calving, calf performance and fertility traits, while a single SNP in the zinc finger protein 215 gene (ZNF215) was associated with milk protein percentage (P ≤ 0.05), progeny carcass weight (P ≤ 0.05), culled cow carcass weight (P ≤ 0.01), angularity (P ≤ 0.01), body depth (P ≤ 0.01), rump width (P ≤ 0.01) and animal stature (P ≤ 0.01). CONCLUSIONS: Of the eight candidate bovine imprinted genes assessed, DNA sequence polymorphisms in six of these genes (CALCR, GRB10, PEG3, RASGRF1, ZIM2 and ZNF215) displayed associations with several of the phenotypes included for analyses. The genotype-phenotype associations detected here are further supported by the biological function of these six genes, each of which plays important roles in mammalian growth, development and physiology. The associations between SNPs within the imprinted PEG3 gene cluster and traits related to calving, calf performance and gestation length suggest that this domain on chromosome 18 may play a role regulating pre-natal growth and development and fertility. SNPs within the bovine ZNF215 gene were associated with bovine growth and body conformation traits and studies in humans have revealed that the human ZNF215 ortholog belongs to the imprinted gene cluster associated with Beckwith-Wiedemann syndrome--a genetic disorder characterised by growth abnormalities. Similarly, the data presented here suggest that the ZNF215 gene may have an important role in regulating bovine growth. Collectively, our results support previous work showing that (candidate) imprinted genes/loci contribute to heritable variation in bovine performance traits and suggest that DNA sequence polymorphisms within these genes/loci represents an important reservoir of genomic markers for future genetic improvement of dairy and beef cattle populations.

Breed- and trait-specific associations define the genetic architecture of calving performance traits in cattle.

Reducing the incidence of both the degree of assistance required at calving, as well as the extent of perinatal mortality (PM) has both economic and societal benefits. The existence of heritable genetic variability in both traits signifies the presence of underlying genomic variability. The objective of the present study was to locate regions of the genome, and by extension putative genes and mutations, that are likely to be underpinning the genetic variability in direct calving difficulty (DCD), maternal calving difficulty (MCD), and PM. Imputed whole-genome single-nucleotide polymorphism (SNP) data on up to 8,304 Angus (AA), 17,175 Charolais (CH), 16,794 Limousin (LM), and 18,474 Holstein-Friesian (HF) sires representing 5,866,712 calving events from descendants were used. Several putative quantitative trait loci (QTL) regions associated with calving performance both within and across dairy and beef breeds were identified, although the majority were both breed- and trait-specific. QTL surrounding and encompassing the myostatin (MSTN) gene were associated (P < 5 × 10-8) with DCD and PM in both the CH and LM populations. The well-known Q204X mutation was the fifth strongest association with DCD in the CH population and accounted for 5.09% of the genetic variance in DCD. In contrast, none of the 259 segregating variants in MSTN were associated (P > × 10-6) with DCD in the LM population but a genomic region 617 kb downstream of MSTN was associated (P < 5 × 10-8). The genetic architecture for DCD differed in the HF population relative to the CH and LM, where two QTL encompassing ZNF613 on Bos taurus autosome (BTA)18 and PLAG1 on BTA14 were identified in the former. Pleiotropic SNP associated with all three calving performance traits were also identified in the three beef breeds; 5 SNP were pleiotropic in AA, 116 in LM, and 882 in CH but no SNP was associated with more than one trait within the HF population. The majority of these pleiotropic SNP were on BTA2 surrounding MSTN and were associated with both DCD and PM. Multiple previously reported, but also novel QTL, associated with calving performance were detected in this large study. These also included QTL regions harboring SNP with the same direction of allele substitution effect for both DCD and MCD thus contributing to a more effective simultaneous selection for both traits.

An index framework founded on the future profit potential of female beef cattle to aid the identification of candidates for culling.

Meticulous culling decisions, coupled with careful breeding decisions, are fundamental to shifting a population distribution in the favorable direction and improving profit per cow. Nevertheless, there is a paucity of easy-to-use dynamic tools to aid in culling decisions in beef cattle. The motivation for the present study was to develop a monetary-based culling tool, here referred to as the Beef Female's Profit Potential (BFPP), to identify females for culling. The BFPP reflects the expected lifetime profitability of an individual female in a herd for the expected remainder of her lifetime; this profit included that of the beef female herself as well as her progeny. The BFPP index framework was composed of 4 subindexes reflecting the value of an animal: (1) as a nulliparae (this was voided if the cow had already calved), (2) for the remainder of her current parity, (3) summed across each of her expected remaining parities, and (4) when she is retained within the herd and not voluntarily culled. Each subindex was comprised of different components reflecting both genetic and non-genetic effects associated with each female. Transition matrices predicting the expected longevity of each female and their expected month of calving were also utilized in calculating the expected remaining lifetime profitability of each female. The BFPP index was validated on 21,102 beef cows as well as their harvested progeny from 875 herds by stratifying the cows, within herd, into 4 strata based on their BFPP. The mean of the within-herd correlation between the BFPP and the Irish national replacement (i.e., breeding) index was, on average, 0.45 indicating the shortcomings of the breeding index as a culling tool. Cows within the top BFPP stratum had a genetic expectation of accruing almost an additional €36 profit per calving, relative to cows within the worst stratum; when validated on the cow's own calving interval and survival performance as well as their progeny's carcass performance, the actual phenotypic value was estimated to be an additional €32 profit per calving. A proportion of this additional profit was due to the harvested progeny of the high BFPP cows having, on average, heavier, more conformed carcasses with less fat cover relative to their poor BFPP contemporaries. This BFPP framework is a useful and easy-to-use tool to aid in producer decision making on the choice of females to voluntarily cull but also on which replacement heifers to graduate into the mature herd.

Animal-level factors associated with the achievement of desirable specifications in Irish beef carcasses graded using the EUROP classification system.

Beef carcasses in Europe are classified on measures of carcass weight, conformation, and fat cover. These measurements provide the basis for payment to producers, with financial penalties for carcasses that do not conform to desirable characteristics. The objective of the present study was to identify animal-level factors associated with the achievement of a desirable carcass weight, conformation score, fat score, and age at harvest, as stipulated by Irish beef processors in accordance with the EUROP carcass classification system. The stipulated specifications were a EUROP conformation score ≥O=, a carcass weight between 270 and 380 kg, a EUROP fat score between 2+ and 4=, and an age at harvest ≤ 30 mo. In the present study, 59% of cattle failed to achieve at least one of these desired specifications. The logit of the probability of achieving the desired specifications was estimated using multivariable logistic regression and carcass data from 4,717,989 cattle finished and harvested in Ireland between the years 2003 and 2017. In comparison to beef-origin carcasses and after accounting for breed differences, the likelihood of dairy-origin carcasses achieving the desired age, conformation, fat, and weight specifications was 0.97, 0.88, 1.14, and 1.05, respectively. In comparison to heifer carcasses, the odds ratio (OR) of bull and steer carcasses simultaneously achieving all of the desired specifications (i.e. the overall specification) was 0.35 and 0.95, respectively. Additionally, after accounting for breed differences, heifers from the dairy herd were half as likely as heifers from the beef herd to achieve the overall specification, whereas the odds of dairy-origin bulls (OR = 3.46) and steers (OR = 2.41) achieving the overall specification was greater than that of their respective beef-origin counterparts. Finally, cattle with a greater breed proportion of Angus were most likely to achieve the overall specification. Results from the present study could provide a deeper understanding as to why animals fail to achieve desirable carcass specifications and could be implemented into the management decisions made on farm to ensure that the supply of beef carcasses that achieve the desired metrics is maximized.

The achievement of a given carcass specification is under moderate genetic control in cattle.

The objective of the present study was to estimate the genetic parameters associated with the achievement of desirable weight, conformation, and fat specifications, represented by a series of binary traits. The desired specifications were those stipulated by Irish beef processors, in accordance with the EUROP carcass grading system, and were represented by a carcass weight between 270 and 380 kg, a fat score between 2+ and 4= (between 6 and 11 on a 15-point scale), and a conformation score of O= or better (≥5 on a 15-point scale). Using data from 58,868 beef carcasses, variance components were estimated using linear mixed models for these binary traits, as well as their underlying continuous measures. Heritability estimates for the continuous traits ranged from 0.63 to 0.73; heritability estimates for the binary traits ranged from 0.05 to 0.19. An additional trait was defined to reflect if all desired carcass specifications were met. All genetic correlations between this trait and the individual contributing binary traits were positive (0.38 to 0.87), while all genetic correlations between this trait and the continuous carcass measures were negative (-0.87 to -0.07). The genetic parameters estimated in the present study signify that potential exists to breed cattle that more consistently achieve desirable carcass metrics at harvest.