Prevalence of Autosomal Monosomy and Trisomy Estimated Using Single Nucleotide Polymorphism Genotype Intensity Chip Information in a Large Population of Juvenile Dairy and Beef Cattle.

Aneuploidy, a genetic condition characterised by the deletion (monosomy) or duplication (trisomy) of a chromosome, has been extensively studied in humans, particularly in the context of trisomy on chromosome 21, also known as Down syndrome. Research on autosomal aneuploidy in live-born cattle has been limited to case reports, resulting in a lack of prevalence estimates of aneuploidy in cattle. Furthermore, the viability or lethality of aneuploidy on specific autosomes in cattle has not been well documented. The objective of this study was to estimate the prevalence of autosomal aneuploidy in a large population of new-born and juvenile beef and dairy cattle using single nucleotide polymorphism (SNP) chip genotype intensity data. Of the population of 779,138 cattle genotyped when younger than 15 months of age, 139 cattle (i.e., 0.017%) were diagnosed with one case of autosomal trisomy. Trisomy in only 10 different autosomes were detected (BTA 4, 6, 12, 15, 20, 24, 26, 27, 28 and 29) albeit the one case of trisomy detected on Bos taurus autosome (BTA) 4 was in an additional population of 341,927 cattle that were genotyped at > 15 months of age and was therefore excluded from prevalence estimates to minimise bias. The prevalence of trisomy per chromosome was generally inversely related to the length of the chromosome. Although the number of affected individuals was few, there was no evidence of differences in prevalence by breed, inbreeding level or parental age. The parental origin of the detected cases of trisomy was maternal for 92% of the cases. No cases of monosomy were detected despite the large dataset, which included calves genotyped at birth, indicating the potential lethal nature of monosomy in cattle. Cytogenetic testing was used to verify three of the animals with detected autosomal trisomy who were still alive. Eighteen of the 139 animals identified with autosomal trisomy were recorded as being stillborn, resulting in a prevalence of autosomal aneuploidy in live-born cattle of 0.015%. Of the 121 live-born cattle with autosomal trisomy, a total of 68 died on farm at, on average (standard deviation), 6.8 (8.7) months of age. All animals with autosomal trisomy on BTA 6, 12, 15, 20 or 24 were either stillborn or died on farm within 15 days of birth. This study is the first report of trisomy on BTA 4, 6, 15, 20 and 27 in live-born cattle, as well as the first to document fertile cows with trisomy on BTA 4, 27 or 28. Given that genotype intensity SNP data from SNP-chips are readily available, identifying animals affected with autosomal aneuploidy as well as quantifying and monitoring the incidence can be easily undertaken.

Prevalence of sex-chromosome aneuploidy estimated using SNP genotype intensity information in a large population of juvenile dairy and beef cattle.

Aneuploidy is a genetic condition characterized by the loss or gain of one or more chromosomes. Aneuploidy affecting the sex chromosomes can lead to infertility in otherwise externally phenotypically normal cattle. Early identification of cattle with sex chromosomal aneuploidy is important to minimize the costs associated with rearing infertile cattle and futile breeding attempts. As most livestock breeding programs routinely genotype their breeding populations using single nucleotide polymorphism (SNP) arrays, this study aimed to assess the feasibility of integrating an aneuploidy screening tool into the existing pipelines that handle dense SNP genotype data. A further objective was to estimate the prevalence of sex chromosome aneuploidy in a population of 146,431 juvenile cattle using available genotype intensity data. Three genotype intensity statistics were used: the LogR Ratio (LRR), R-value (the sum of X and Y SNP probe intensities), and B-allele frequency (BAF) measurements. Within the female-verified population of 124,958 individuals, the estimated prevalence rate was 0.0048% for XO, 0.0350% for XXX, and 0.0004% for XXY. The prevalence of XXY in the male-verified population was 0.0870% (i.e., 18 out of 20,670 males). Cytogenetic testing was used to verify 2 of the XXX females who were still alive. The proposed approach can be readily integrated into existing genomic pipelines, serving as an efficient, large-scale screening tool for aneuploidy. Its implementation could enable the early identification of infertile animals with sex-chromosome aneuploidy.

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.

Genetic control of temperament traits across species: association of autism spectrum disorder risk genes with cattle temperament.

BACKGROUND: Temperament traits are of high importance across species. In humans, temperament or personality traits correlate with psychological traits and psychiatric disorders. In cattle, they impact animal welfare, product quality and human safety, and are therefore of direct commercial importance. We hypothesized that genetic factors that contribute to variation in temperament among individuals within a species will be shared between humans and cattle. Using imputed whole-genome sequence data from 9223 beef cattle from three cohorts, a series of genome-wide association studies was undertaken on cattle flight time, a temperament phenotype measured as the time taken for an animal to cover a short-fixed distance after release from an enclosure. We also investigated the association of cattle temperament with polymorphisms in bovine orthologs of risk genes for neuroticism, schizophrenia, autism spectrum disorders (ASD), and developmental delay disorders in humans. RESULTS: Variants with the strongest associations were located in the bovine orthologous region that is involved in several behavioural and cognitive disorders in humans. These variants were also partially validated in independent cattle cohorts. Genes in these regions (BARHL2, NDN, SNRPN, MAGEL2, ABCA12, KIFAP3, TOPAZ1, FZD3, UBE3A, and GABRA5) were enriched for the GO term neuron migration and were differentially expressed in brain and pituitary tissues in humans. Moreover, variants within 100 kb of ASD susceptibility genes were associated with cattle temperament and explained 6.5% of the total additive genetic variance in the largest cattle cohort. The ASD genes with the most significant associations were GABRB3 and CUL3. Using the same 100 kb window, a weak association was found with polymorphisms in schizophrenia risk genes and no association with polymorphisms in neuroticism and developmental delay disorders risk genes. CONCLUSIONS: Our analysis showed that genes identified in a meta-analysis of cattle temperament contribute to neuron development functions and are differentially expressed in human brain tissues. Furthermore, some ASD susceptibility genes are associated with cattle temperament. These findings provide evidence that genetic control of temperament might be shared between humans and cattle and highlight the potential for future analyses to leverage results between species.

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).

Associations between polymorphisms in the myostatin gene with calving difficulty and carcass merit in cattle.

A fully functional myostatin gene inhibits muscle fiber growth. The objective of the present study was to quantify the association between 21 known myostatin mutations with both calving and carcass traits in 12 cattle breeds. The myostatin genotypes of 32,770 dam-progeny combinations were used in the association analysis of calving dystocia, with the genotypes of 129,803 animals used in the mixed model association analyses of carcass weight, conformation, and fat score. The mixed model included additive genetic, maternal, and permanent environmental effects where appropriate. The mutant genotypes of nt821, Q204X, and F94L were all associated (P < 0.01) with more calving difficulty when present in either the dam or the progeny. The nt821 deletion had the greatest association with calving difficulty when the homozygous deletion was present in either the calf (0.37 points greater calving difficulty score relative to calves carrying no copies of the deletion based on a one to four scale) or the dam (1.30 points greater calving difficulty score relative to dams carrying no copies of the deletion), although the association between the calf's nt821 genotype and calving difficulty differed depending on the nt821 genotype of the dam. With the exception of nt748_78, nt414, and nt374_51, all other seven segregating myostatin variants were associated (range of allele substitution effect size relative to animals with no copies of the mutant allele) with carcass weight (2.36 kg lighter to 15.56 kg heavier), all 10 segregating variants with conformation (0.15 units less conformed to 2.24 units more conformed assessed on a scale of 1 to 15), and all segregating variants other than E226X with carcass fat (0.23 units less carcass fat cover to 3.85 units more carcass fat cover assessed on a scale of 1 to 15). Of these, the F94L, Q204X, and nt821 mutations generally had the greatest association with all three carcass traits, giving rise to heavier and more conformed carcasses. Despite the antagonistic genetic relationship between calving difficulty and carcass traits, the nt374_51, F94L, and E226X mutations were all associated with improved carcass merit while having minimal expected consequences on calving difficulty. Thus, animals carrying these mutation(s) may have favorable genetic merit for calving difficulty and carcass merit. Furthermore, depending on the dam genotype, a bull with two copies of the nt821 mutation can produce progeny with improved carcass merit while minimizing calving problems.

The objective of the present study was to quantify the association between 21 known myostatin mutations with calving difficulty, carcass fat, carcass conformation, and carcass weight in 12 prominent cattle breeds. Out of all segregating myostatin variants, the nt821 deletion had the greatest observed association with calving difficulty when the homozygous deletion was carried by either the calf or the dam. However, the association between the calf's nt821 genotype and calving difficulty varied depending on the nt821 genotype of the dam. The F94L, Q204X, and nt821 mutations generally had the greatest association with all three carcass traits, resulting in heavier and more conformed carcasses. The nt374_51, F94L, and E226X mutations were all associated with improved carcass merit while having minimal expected consequences on calving difficulty; therefore, animals carrying these mutations could potentially have desirable genetic merit for both calving difficulty and carcass merit. Similarly, depending on the genotype of the dam, a bull carrying two copies of the nt821 deletion could give rise to progeny that have improved carcass merit while minimizing the associated risk of calving difficulty.

Runs of homozygosity and population history in cattle.

BACKGROUND: Runs of homozygosity (ROH) are contiguous lengths of homozygous genotypes that are present in an individual due to parents transmitting identical haplotypes to their offspring. The extent and frequency of ROHs may inform on the ancestry of an individual and its population. Here we use high density (n = 777,962) bi-allelic SNPs in a range of cattle breed samples to correlate ROH with the pedigree-based inbreeding coefficients and to validate subsequent analyses using 54,001 SNP genotypes. This study provides a first testing of the inference drawn from ROH through comparison with estimates of inbreeding from calculations based on the detailed pedigree data available for several breeds. RESULTS: All animals genotyped on the HD panel displayed at least one ROH that was between 1-5 Mb in length with certain regions of the genome more likely to be involved in a ROH than others. Strong correlations (r = 0.75, p < 0.0001) existed between the pedigree-based inbreeding coefficient and a statistic based on sum of ROH of length > 0.5 KB and suggests that in the absence of an animal's pedigree data, the extent of a genome under ROH may be used to infer aspects of recent population history even from relatively few samples. CONCLUSIONS: Our findings suggest that ROH are frequent across all breeds but differing patterns of ROH length and burden illustrate variations in breed origins and recent management.

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.

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.

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.

Genomic Regions Associated With Skeletal Type Traits in Beef and Dairy Cattle Are Common to Regions Associated With Carcass Traits, Feed Intake and Calving Difficulty.

Linear type traits describing the skeletal characteristics of an animal are moderately to strongly genetically correlated with a range of other performance traits in cattle including feed intake, reproduction traits and carcass merit; thus, type traits could also provide useful insights into the morphological differences among animals underpinning phenotypic differences in these complex traits. The objective of the present study was to identify genomic regions associated with five subjectively scored skeletal linear traits, to determine if these associated regions are common in multiple beef and dairy breeds, and also to determine if these regions overlap with those proposed elsewhere to be associated with correlated performance traits. Analyses were carried out using linear mixed models on imputed whole genome sequence data separately in 1,444 Angus, 1,129 Hereford, 6,433 Charolais, 8,745 Limousin, 1,698 Simmental, and 4,494 Holstein-Friesian cattle, all scored for the linear type traits. There was, on average, 18 months difference in age at assessment of the beef versus the dairy animals. While the majority of the identified quantitative trait loci (QTL), and thus genes, were both trait-specific and breed-specific, a large-effect pleiotropic QTL on BTA6 containing the NCAPG and LCORL genes was associated with all skeletal traits in the Limousin population and with wither height in the Angus. Other than that, little overlap existed in detected QTLs for the skeletal type traits in the other breeds. Only two QTLs overlapped the beef and dairy breeds; both QTLs were located on BTA5 and were associated with height in both the Angus and the Holstein-Friesian, despite the difference in age at assessment. Several detected QTLs in the present study overlapped with QTLs documented elsewhere that are associated with carcass traits, feed intake, and calving difficulty. While most breeding programs select for the macro-traits like carcass weight, carcass conformation, and feed intake, the higher degree of granularity with selection on the individual linear type traits in a multi-trait index underpinning the macro-level goal traits, presents an opportunity to help resolve genetic antagonisms among morphological traits in the pursuit of the animal with optimum performance metrics.

Genomic Regions Associated With Gestation Length Detected Using Whole-Genome Sequence Data Differ Between Dairy and Beef Cattle.

While many association studies exist that have attempted to relate genomic markers to phenotypic performance in cattle, very few have considered gestation length as a phenotype, and of those that did, none used whole genome sequence data from multiple breeds. The objective of the present study was therefore to relate imputed whole genome sequence data to estimated breeding values for gestation length using 22,566 sires (representing 2,262,706 progeny) of multiple breeds [Angus (AA), Charolais (CH), Holstein-Friesian (HF), and Limousin (LM)]. The associations were undertaken within breed using linear mixed models that accounted for genomic relatedness among sires; a separate association analysis was undertaken with all breeds analysed together but with breed included as a fixed effect in the model. Furthermore, the genome was divided into 500 kb segments and whether or not segments harboured a single nucleotide polymorphism (SNP) with a P ≤ 1 × 10-4 common to different combinations of breeds was determined. Putative quantitative trait loci (QTL) regions associated with gestation length were detected in all breeds; significant associations with gestation length were only detected in the HF population and in the across-breed analysis of all 22,566 sires. Twenty-five SNPs were significantly associated (P ≤ 5 × 10-8) with gestation length in the HF population. Of the 25 significant SNPs, 18 were located within three QTLs on Bos taurus autosome number (BTA) 18, six were in two QTL on BTA19, and one was located within a QTL on BTA7. The strongest association was rs381577268, a downstream variant of ZNF613 located within a QTL spanning from 58.06 to 58.19 Mb on BTA18; it accounted for 1.37% of the genetic variance in gestation length. Overall there were 11 HF animals within the edited dataset that were homozygous for the T allele at rs381577268 and these had a 3.3 day longer (P < 0.0001) estimated breeding value (EBV) for gestation length than the heterozygous animals and a 4.7 day longer (P < 0.0001) EBV for gestation length than the homozygous CC animals. The majority of the 500 kb windows harboring a SNP with a P ≤ 1 × 10-4 were unique to a single breed and no window was shared among all four breeds for gestation length, suggesting any QTLs identified are breed-specific associations.

Characterization of copy number variants in a large multibreed population of beef and dairy cattle using high-density single nucleotide polymorphism genotype data.

Copy number variants (CNVs) are a form of genomic variation that changes the structure of the genome through deletion or duplication of stretches of DNA. The objective of the present study was to characterize CNVs in a large multibreed population of beef and dairy bulls. The CNVs were called on the autosomes of 5,551 cattle from 22 different beef and dairy breeds, using 2 freely available software suites, QuantiSNP and PennCNV. All CNVs were classified into either deletions or duplications. The median concordance between PennCNV and QuantiSNP, per animal, was 18.5% for deletions and 0% for duplications. The low concordance rate between PennCNV and QuantiSNP indicated that neither algorithm, by itself, could identify all CNVs in the population. In total, PennCNV and QuantiSNP collectively identified 747,129 deletions and 432,523 duplications; 80.2% of all duplications and 69.1% of all deletions were present only once in the population. Only 0.154% of all CNVs identified were present in more than 50 animals in the population. The distribution of the percentage of the autosomes that were composed of deletions, per animal, was positively skewed, as was the distribution for the percentage of the autosomes that were composed of duplications, per animal. The first quartile, median, and third quartile of the distribution of the percentage of the autosomes that were composed of deletions were 0.019%, 0.037%, and 0.201%, respectively. The first quartile, median, and third quartile of the distribution of the percentage of the autosomes that were composed of duplications were 0.013%, 0.028%, and 0.076%, respectively. The distributions of the number of deletions and duplications per animal were both positively skewed. The interquartile range for the number of deletions per animal in the population was between 16 and 117, whereas for duplications it was between 8 and 23. Per animal, there tended to be twice as many deletions as duplications. The distribution of the length of deletions was positively skewed, as was the distribution of the length of duplications. The interquartile range for the length of deletions in the population was between 25 and 101 kb, and for duplications the interquartile range was between 46 and 235 kb. Per animal, duplications tended to be twice as long as deletions. This study provides a description of the characteristics and distribution of CNVs in a large multibreed population of beef and dairy cattle.

Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals.

Stature is affected by many polymorphisms of small effect in humans 1 . In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10-8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.

The distribution of runs of homozygosity and selection signatures in six commercial meat sheep breeds.

Domestication and the subsequent selection of animals for either economic or morphological features can leave a variety of imprints on the genome of a population. Genomic regions subjected to high selective pressures often show reduced genetic diversity and frequent runs of homozygosity (ROH). Therefore, the objective of the present study was to use 42,182 autosomal SNPs to identify genomic regions in 3,191 sheep from six commercial breeds subjected to selection pressure and to quantify the genetic diversity within each breed using ROH. In addition, the historical effective population size of each breed was also estimated and, in conjunction with ROH, was used to elucidate the demographic history of the six breeds. ROH were common in the autosomes of animals in the present study, but the observed breed differences in patterns of ROH length and burden suggested differences in breed effective population size and recent management. ROH provided a sufficient predictor of the pedigree inbreeding coefficient, with an estimated correlation between both measures of 0.62. Genomic regions under putative selection were identified using two complementary algorithms; the fixation index and hapFLK. The identified regions under putative selection included candidate genes associated with skin pigmentation, body size and muscle formation; such characteristics are often sought after in modern-day breeding programs. These regions of selection frequently overlapped with high ROH regions both within and across breeds. Multiple yet uncharacterised genes also resided within putative regions of selection. This further substantiates the need for a more comprehensive annotation of the sheep genome as these uncharacterised genes may contribute to traits of interest in the animal sciences. Despite this, the regions identified as under putative selection in the current study provide an insight into the mechanisms leading to breed differentiation and genetic variation in meat production.

Novel Graphical Analyses of Runs of Homozygosity among Species and Livestock Breeds.

Runs of homozygosity (ROH), uninterrupted stretches of homozygous genotypes resulting from parents transmitting identical haplotypes to their offspring, have emerged as informative genome-wide estimates of autozygosity (inbreeding). We used genomic profiles based on 698 K single nucleotide polymorphisms (SNPs) from nine breeds of domestic cattle (Bos taurus) and the European bison (Bison bonasus) to investigate how ROH distributions can be compared within and among species. We focused on two length classes: 0.5-15 Mb to investigate ancient events and >15 Mb to address recent events (approximately three generations). For each length class, we chose a few chromosomes with a high number of ROH, calculated the percentage of times a SNP appeared in a ROH, and plotted the results. We selected areas with distinct patterns including regions where (1) all groups revealed an increase or decrease of ROH, (2) bison differed from cattle, (3) one cattle breed or groups of breeds differed (e.g., dairy versus meat cattle). Examination of these regions in the cattle genome showed genes potentially important for natural and human-induced selection, concerning, for example, meat and milk quality, metabolism, growth, and immune function. The comparative methodology presented here permits visual identification of regions of interest for selection, breeding programs, and conservation.