An autosomal recessive variant in PYGM causes myophosphorylase deficiency in Red Angus composite cattle.

BACKGROUND: Between 2020 and 2022, eight calves in a Nebraska herd (composite Simmental, Red Angus, Gelbvieh) displayed exercise intolerance during forced activity. In some cases, the calves collapsed and did not recover. Available sire pedigrees contained a paternal ancestor within 2-4 generations in all affected calves. Pedigrees of the calves' dams were unavailable, however, the cows were ranch-raised and retained from prior breeding seasons, where bulls used for breeding occasionally had a common ancestor. Therefore, it was hypothesized that a de novo autosomal recessive variant was causative of exercise intolerance in these calves. RESULTS: A genome-wide association analysis utilizing SNP data from 6 affected calves and 715 herd mates, followed by whole-genome sequencing of 2 affected calves led to the identification of a variant in the gene PYGM (BTA29:g.42989581G > A). The variant, confirmed to be present in the skeletal muscle transcriptome, was predicted to produce a premature stop codon (p.Arg650*). The protein product of PYGM, myophosphorylase, breaks down glycogen in skeletal muscle. Glycogen concentrations were fluorometrically assayed as glucose residues demonstrating significantly elevated glycogen concentrations in affected calves compared to cattle carrying the variant and to wild-type controls. The absence of the PYGM protein product in skeletal muscle was confirmed by immunohistochemistry and label-free quantitative proteomics analysis; muscle degeneration was confirmed in biopsy and necropsy samples. Elevated skeletal muscle glycogen persisted after harvest, resulting in a high pH and dark-cutting beef, which is negatively perceived by consumers and results in an economic loss to the industry. Carriers of the variant did not exhibit differences in meat quality or any measures of animal well-being. CONCLUSIONS: Myophosphorylase deficiency poses welfare concerns for affected animals and negatively impacts the final product. The association of the recessive genotype with dark-cutting beef further demonstrates the importance of genetics to not only animal health but to the quality of their product. Although cattle heterozygous for the variant may not immediately affect the beef industry, identifying carriers will enable selection and breeding strategies to prevent the production of affected calves.

Variance component estimates for growth traits in beef cattle using selected variants from imputed low-pass sequence data.

A beef cattle population (n = 2,343) was used to assess the impact of variants identified from the imputed low-pass sequence (LPS) on the estimation of variance components and genetic parameters of birth weight (BWT) and post-weaning gain (PWG). Variants were selected based on functional impact and were partitioned into four groups (low, modifier, moderate, high) based on predicted functional impact and re-partitioned based on the consequence of mutation, such as missense and untranslated region variants, into six groups (G1-G6). Each subset was used to construct a genomic relationship matrix (GRM) for univariate animal models. Multiple analyses were conducted to compare the proportion of additive genetic variation explained by the different subsets individually and collectively, and these estimates were benchmarked against all LPS variants in a single GRM and array (e.g., GeneSeek Genomic Profiler 100K) genotypes. When all variants were included in a single GRM, heritability estimates for BWT and PWG were 0.43 ±â€…0.05 and 0.38 ±â€…0.05, respectively. Heritability estimates for BWT ranged from 0.10 to 0.42 dependent on which variant subsets were included. Similarly, estimates for PWG ranged from 0.05 to 0.38. Results showed that variants in the subsets modifier and G1 (untranslated region) yielded the highest heritability estimates and were similar to the inclusion of all variants, while estimates from GRM containing only variants in the categories High, G4 (non-coding transcript exon), and G6 (start and stop loss/gain) were the lowest. All variants combined provided similar heritability estimates to chip genotypes and provided minimal to no additional information when combined with chip data. This suggests that the chip single nucleotide polymorphisms and the variants from LPS predicted to be less consequential are in relatively high linkage disequilibrium with the underlying causal variants as a whole and sufficiently spread throughout the genome to capture larger proportions of additive genetic variation.

Animals from a crossbred beef cattle population were sequenced at low depth (i.e., 0.5×) and different subsets of selected imputed variants were investigated relative to their ability to explain variation in birth weight (BWT) and post-weaning gain (PWG). Variants were classified by both their predicted functional impact and by the consequence of the mutation and partitioned into subsets within these two criteria. When ~ 1 million variants were included in the same genomic relationship matrix, heritability estimates were similar to a 100k chip array. Heritability estimates for BWT ranged from 0.10 to 0.42 dependent on which variant subsets were included. Similarly, estimates for PWG ranged from 0.05 to 0.38. Differences in minor allele frequency were observed among subsets and these differences likely contributed to differences in heritability estimates. Results suggest that linkage disequilibrium between the variants categorized as being less consequential and underlying causal variants is high as indicated by the high percentage of variation explained.

The Influence of Presbylarynx Status on Objective Measures of the Aging Voice.

OBJECTIVE: The primary objective of this study was to assess objective voice measures in an elderly population representative of those seen in a tertiary laryngology practice, stratified by sex and presbylarynx status, and compare their measures to each other and to a cohort of young adult patients aged 40 years or less. The secondary objectives of this study were to evaluate and compare the strobovideolaryngoscopy findings across all groups and compare the voice complaints and subjective questionnaire results between the presbylarynx and non-presbylarynx groups. METHODS: Two hundred and eighty-six adult voice patients (147 females/139 males) were included in this study and stratified into one of three groups: (1) young adults aged 40 years or less (n = 122), (2) patients over the age of 60 without presbylarynx (n = 78), and (3) patients over the age of 60 with a diagnosis of presbylarynx (n = 86). The acoustic analysis included fundamental frequency (F0), voice intensity, standard deviation of the fundamental frequency (SDFF), jitter (Jitt), relative average perturbation (RAP), shimmer (Shim), noise-to-harmonic ratio (NHR), and others. The aerodynamic and pulmonary assessment included maximum phonation time (MPT), S/Z ratio, mean flow rate (MFR), forced expiratory volume in 1 second (FEV1), and maximal mid-expiratory flow (FEF25-75). Coexisting vocal fold conditions and pathologies were also characterized and compared. Statistical analysis was performed using SPSS 28.0.0.0 (IBM, Armonk, NY). All tests were performed in two-tailed, and a P value of less than 0.05 was considered statistically significant. RESULTS: Assessment of vocal fold features revealed a significantly higher prevalence of benign vocal fold lesions in the young adult group for males and females compared to both elderly groups but significantly lower prevalence of vocal fold edema only in young adult females compared to the elderly female groups. Among males, young adults differed significantly from both elderly groups with regard to SDFF, Shim, FEV1, and FEF25-75. However, Jitt and RAP only differed significantly between the young adult and presbylarynx groups. Among females, young adults differed significantly from both elderly groups for F0, SDFF, Jitt, RAP, NHR, CPP, MFR, FEV1, and FEF25-75. However, the non-presbylarynx group had a significantly lower S/Z ratio than the young adult and presbylarynx groups. A comparison of voice complaints between elderly groups revealed breathiness to be significantly more common in the presbylarynx group compared to the non-presbylarynx group, but no other significant differences were found in voice complaints or questionnaire scores. CONCLUSION: When interpreting objective voice measures, it is critical to consider differences in vocal fold features alongside age-related changes. In addition, sex-related differences in anatomy and the aging process may explain discrepancies in significant findings between young adults and elderly patients stratified by presbylarynx status. However, presbylarynx status alone appears insufficient to generate significant differences in most objective voice measures among the elderly. Yet, presbylarynx status may be sufficient to generate differences in perceptual voice symptoms.

Patient perspectives on peritoneal dialysis (PD) and the PD catheter: Strategies and Solutions.

INTRODUCTION: Peritoneal dialysis (PD) catheter complications reduce quality of life and increase risks for hospitalizations, for unplanned transitions to haemodialysis and for death. Patient PD catheter management is crucial for safe, sustained PD. Patient perspectives on strategies for living with PD and using a PD catheter may inform efforts to reduce PD catheter complications, increase individual patient PD modality persistence, and thus increase overall home dialysis prevalence. METHODS: We interviewed 32 adult PD patients in Nashville, Tennessee. Qualitative analyses included (1) isolation of themes, (2) development of a coding system and (3) creation of a conceptual framework using an inductive-deductive approach. RESULTS: Challenges identified by patients as important included drain pain, difficulty eating and sleeping, and fear of peritonitis. Coping strategies included repositioning while draining, adjusting eating patterns, and development of PD patient and helper knowledge and confidence, especially at home after initial training. Patients described a trial-and-error iterative process of trying multiple strategies with input from multiple sources, which led to individualised solutions. CONCLUSIONS: The trial-and-error process may be crucial for maintaining PD. Individual patient success with PD may be promoted by creating expectations during training that a solution may require multiple attempts, and by a reimbursement policy that supports robust nursing support for safe progression through the trial-and-error process, particularly in the first few months for incident patients. Interventions to support patient motivation and optimal coping behaviour may also support an increase in PD modality duration for individual patients, and thus increase overall PD prevalence.

Strategies for accommodating gene-edited sires and their descendants in genetic evaluations.

Gene editing has the potential to expedite the rate of genetic gain for complex traits. However, changing nucleotides (i.e., QTN) in the genome can affect the additive genetic relationship among individuals and, consequently, impact genetic evaluations. Therefore, the objectives of this study were to estimate the impact of including gene-edited individuals in the genetic evaluation and investigate modeling strategies to mitigate potential errors. For that, a beef cattle population was simulated for nine generations (N = 13,100). Gene-edited sires (1, 25, or 50) were introduced in generation 8. The number of edited QTN was 1, 3, or 13. Genetic evaluations were performed using pedigree, genomic data, or a combination of both. Relationships were weighted based on the effect of the edited QTN. Comparisons were made using the accuracy, average absolute bias, and dispersion of the estimated breeding values (EBV). In general, the EBV of the first generation of progeny of gene-edited sires were associated with greater average absolute bias and overdispersion than the EBV of the progeny of non-gene-edited sires (P ≤ 0.001). Weighting the relationship matrices increased (P ≤ 0.001) the accuracy of EBV when the gene-edited sires were introduced by 3% and decreased (P ≤ 0.001) the average absolute bias and dispersion for the progeny of gene-edited sires. For the second generation of descendants of gene-edited sires, the absolute bias increased as the number of edited alleles increased; however, the rate of increase in absolute bias was 0.007 for each allele edited when the relationship matrices were weighted compared with 0.10 when the relationship matrices were not weighted. Overall, when gene-edited sires are included in genetic evaluations, error is introduced in the EBV, such that the EBV of progeny of gene-edited sires are underestimated. Hence, the progeny of gene-edited sires would be less likely to be selected to be parents of the next generation than what was expected based on their true genetic merit. Therefore, modeling strategies such as weighting the relationship matrices are essential to avoid incorrect selection decisions if animals that have been edited for QTN underlying complex traits are introduced into genetic evaluations.

Coupling gene editing, a technology with the potential to make specific changes to DNA sequence (e.g., quantitative trait nucleotide, QTN), with genomic selection can generate faster genetic gain in economically important traits. However, gene editing would impact the genetic relationship among individuals and, consequently, genetic evaluations. The objectives of this study were to understand how gene editing impacts genetic prediction and develop strategies to mitigate potential errors in estimated breeding values (EBV). A beef cattle population was simulated (N = 13,100; nine generations) with the introduction of gene-edited sires in generation 8. Genetic evaluations were performed using pedigree and genomic data. Relationships were weighted based on the effect of the edited QTN. In general, the EBV of the first generation of progeny of gene-edited sires were associated with greater average absolute bias and overdispersion than the EBV of the progeny of non-gene-edited sires. Weighting the relationship matrices decreased the average absolute bias and dispersion for the progeny of gene-edited sires. For the second generation of descendants of gene-edited sires, the absolute bias increased by 0.10 for each allele edited. By weighting the relationship matrices, the rate of increase in absolute bias per allele decreased to 0.007. Therefore, when gene-edited sires are included in genetic evaluations, strategies such as weighting the relationship matrices should be considered to avoid incorrect selection decisions.

A novel role for trithorax in the gene regulatory network for a rapidly evolving fruit fly pigmentation trait.

Animal traits develop through the expression and action of numerous regulatory and realizator genes that comprise a gene regulatory network (GRN). For each GRN, its underlying patterns of gene expression are controlled by cis-regulatory elements (CREs) that bind activating and repressing transcription factors. These interactions drive cell-type and developmental stage-specific transcriptional activation or repression. Most GRNs remain incompletely mapped, and a major barrier to this daunting task is CRE identification. Here, we used an in silico method to identify predicted CREs (pCREs) that comprise the GRN which governs sex-specific pigmentation of Drosophila melanogaster. Through in vivo assays, we demonstrate that many pCREs activate expression in the correct cell-type and developmental stage. We employed genome editing to demonstrate that two CREs control the pupal abdomen expression of trithorax, whose function is required for the dimorphic phenotype. Surprisingly, trithorax had no detectable effect on this GRN's key trans-regulators, but shapes the sex-specific expression of two realizator genes. Comparison of sequences orthologous to these CREs supports an evolutionary scenario where these trithorax CREs predated the origin of the dimorphic trait. Collectively, this study demonstrates how in silico approaches can shed novel insights on the GRN basis for a trait's development and evolution.

Genetic and phenotypic associations of mitochondrial DNA copy number, SNP, and haplogroups with growth and carcass traits in beef cattle.

Mitochondrial DNA copy number (mtDNA CN) is heritable and easily obtained from low-pass sequencing (LPS). This study investigated the genetic correlation of mtDNA CN with growth and carcass traits in a multi-breed and crossbred beef cattle population. Blood, leucocyte, and semen samples were obtained from 2,371 animals and subjected to LPS that resulted in nuclear DNA (nuDNA) and mtDNA sequence reads. Mitochondrial DNA CN was estimated as the ratio of mtDNA to nuDNA coverages. Variant calling was performed from mtDNA, and 11 single nucleotide polymorphisms (SNP) were identified in the population. Samples were classified in taurine haplogroups. Haplogroup and mtDNA type were further classified based on the 11 segregating SNP. Growth and carcass traits were available for between 7,249 and 60,989 individuals. Associations of mtDNA CN, mtDNA haplogroups, mtDNA types, and mtDNA SNP with growth and carcass traits were estimated with univariate animal models, and genetic correlations were estimated with a bivariate animal model based on pedigree. Mitochondrial DNA CN tended (P-value ≤0.08) to be associated with birth weight and weaning weight. There was no association (P-value >0.10) between mtDNA SNP, haplogroups, or types with growth and carcass traits. Genetic correlation estimates of mtDNA CN were -0.30 ± 0.16 with birth weight, -0.31 ± 0.16 with weaning weight, -0.15 ± 0.14 with post-weaning gain, -0.11 ± 0.19 with average daily dry-matter intake, -0.04 ± 0.22 with average daily gain, -0.29 ± 0.13 with mature cow weight, -0.11 ± 0.13 with slaughter weight, -0.14 ± 0.13 with carcass weight, -0.07 ± 0.14 with carcass backfat, 0.14 ± 0.14 with carcass marbling, and -0.06 ± 0.14 with ribeye area. In conclusion, mtDNA CN was negatively correlated with most traits investigated, and the genetic correlation was stronger with growth traits than with carcass traits.

This study investigated mitochondrial DNA copy number (mtDNA CN) as a potential genetic indicator of growth and carcass traits in a composite beef cattle population. Mitochondrial DNA CN was previously shown to be under genetic control. The current study estimated the genetic relationship of mtDNA CN with growth and carcass traits. Blood, leucocyte, and semen samples were obtained from 2,371 animals and subjected to whole-genome sequencing at a low depth that resulted in nuclear DNA and mtDNA sequence reads. Mitochondrial DNA CN was estimated as the ratio of mtDNA to nuclear DNA coverages. Growth and carcass traits were available for between 7,249 and 60,989 individuals. Genetic parameters were estimated from an animal model based on pedigree. Genetic correlation estimates of mtDNA CN with growth and carcass traits were low to moderate and mostly negative. These indicate that selection for lower mtDNA would be associated with an increase in birth weight, weaning weight, post-weaning gain, average daily dry-matter intake, mature cow weight, slaughter weight, and carcass weight. Therefore, the by-product of whole-genome sequencing at a low depth could be used as an indicator trait for growth and carcass traits in genetic evaluations, but the genetic relationships are not likely strong enough to prioritize mtDNA ahead of routinely used indicator traits.

Breeding Sustainable Beef Cows: Reducing Weight and Increasing Productivity.

Programs for sustainable beef production are established, but the specific role of beef cows in these systems is not well defined. This work characterized cows for two traits related to sustainability, cow weight (CW) and cumulative weight weaned (WtW). Cow weight indicates nutrient requirements and enteric methane emissions. Cumulative weight weaned reflects reproductive performance and avoidance of premature culling for characteristics related to animal health, welfare, and worker safety. Both traits were evaluated with random regression models with records from a crossbred population representing 18 breeds that conduct US national cattle evaluations. The genomic REML analyses included additive and dominance components, with relationships among 22,776 animals constructed from genotypes of 181,286 potentially functional variants imputed from a low-pass sequence. Projected to 8 years of age, the additive heritability estimate for CW was 0.57 and 0.11 for WtW. Dominance heritability was 0.02 for CW and 0.19 for WtW. Many variants with significant associations with CW were within previously described quantitative trait loci (QTL) for growth-related production, meat, and carcass traits. Significant additive WtW variants were covered by QTL for traits related to reproduction and structural soundness. All breeds contributed to groups of cows with high and low total genetic values (additive + dominance effects) for both traits. The high WtW cows and cows above the WtW mean but below the CW mean had larger heterosis values and fewer bases in runs of homozygosity. The high additive heritability of CW and dominance effects on WtW indicate that breeding to improve beef cow sustainability should involve selection to reduce CW and mate selection to maintain heterosis and reduce runs of homozygosity.

DNA methylation profile in beef cattle is influenced by additive genetics and age.

DNA methylation (DNAm) has been considered a promising indicator of biological age in mammals and could be useful to increase the accuracy of phenotypic prediction in livestock. The objectives of this study were to estimate the heritability and age effects of site-specific DNAm (DNAm level) and cumulative DNAm across all sites (DNAm load) in beef cattle. Blood samples were collected from cows ranging from 217 to 3,192 days (0.6 to 8.7 years) of age (n = 136). All animals were genotyped, and DNAm was obtained using the Infinium array HorvathMammalMethylChip40. Genetic parameters for DNAm were obtained from an animal model based on the genomic relationship matrix, including the fixed effects of age and breed composition. Heritability estimates of DNAm levels ranged from 0.18 to 0.72, with a similar average across all regions and chromosomes. Heritability estimate of DNAm load was 0.45. The average age effect on DNAm level varied among genomic regions. The DNAm level across the genome increased with age in the promoter and 5' UTR and decreased in the exonic, intronic, 3' UTR, and intergenic regions. In addition, DNAm level increased with age in regions enriched in CpG and decreased in regions deficient in CpG. Results suggest DNAm profiles are influenced by both genetics and the environmental effect of age in beef cattle.

A Five Year Randomized Controlled Trial to Assess the Efficacy and Antibody Responses to a Commercial and Autogenous Vaccine for the Prevention of Infectious Bovine Keratoconjunctivitis.

A randomized control trial was performed over a five-year period to assess the efficacy and antibody response induced by autogenous and commercial vaccine formulations against infectious bovine keratoconjunctivitis (IBK). Calves were randomly assigned each year to one of three arms: an autogenous vaccine treatment that included Moraxella bovis (M. bovis), Moraxella bovoculi, and Mycoplasma bovoculi antigens, a commercial M. bovis vaccine treatment, or a sham vaccine treatment that consisted only of adjuvant. A total of 1198 calves were enrolled in the study. Calves were administered the respective vaccines approximately 21 days apart, just prior to turnout on summer pastures. Treatment effects were analyzed for IBK incidence, retreatment incidence, 205-day adjusted weaning weights, and antibody response to the type IV pilus protein (pili) of M. bovis as measured by a novel indirect enzyme-linked immunosorbent screening assay (ELISA). Calves vaccinated with the autogenous formulation experienced a decreased cumulative incidence of IBK over the entire study compared to those vaccinated with the commercial and sham formulations (24.5% vs. 30.06% vs. 30.3%, respectively, p = 0.25), and had less IBK cases that required retreatment compared to the commercial and sham formulations (21.4% vs. 27.9% vs. 34.3%, respectively, p = 0.15), but these differences were not significant. The autogenous formulation induced a significantly stronger antibody response than the commercial (p = 0.022) and sham formulations (p = 0.001), but antibody levels were not significantly correlated with IBK protection (p = 0.37).

Using pooled data for genomic prediction in a bivariate framework with missing data.

Pooling samples to derive group genotypes can enable the economically efficient use of commercial animals within genetic evaluations. To test a multivariate framework for genetic evaluations using pooled data, simulation was used to mimic a beef cattle population including two moderately heritable traits with varying genetic correlations, genotypes and pedigree data. There were 15 generations (n = 32,000; random selection and mating), and the last generation was subjected to genotyping through pooling. Missing records were induced in two ways: (a) sequential culling and (b) random missing records. Gaps in genotyping were also explored whereby genotyping occurred through generation 13 or 14. Pools of 1, 20, 50 and 100 animals were constructed randomly or by minimizing phenotypic variation. The EBV was estimated using a bivariate single-step genomic best linear unbiased prediction model. Pools of 20 animals constructed by minimizing phenotypic variation generally led to accuracies that were not different than using individual progeny data. Gaps in genotyping led to significantly different EBV accuracies (p < .05) for sires and dams born in the generation nearest the pools. Pooling of any size generally led to larger accuracies than no information from generation 15 regardless of the way missing records arose, the percentage of records available or the genetic correlation. Pooling to aid in the use of commercial data in genetic evaluations can be utilized in multivariate cases with varying relationships between the traits and in the presence of systematic and randomly missing phenotypes.

Influence of environmental factors and genetic variation on mitochondrial DNA copy number.

Mitochondrial DNA copy number (mtDNA CN) has been shown to be highly heritable and associated with traits of interest in humans. However, studies are lacking in the literature for livestock species such as beef cattle. In this study, 2,371 individuals from a crossbred beef population comprising the Germplasm Evaluation program from the U.S. Meat Animal Research Center had samples of blood, leucocyte, or semen collected for low-pass sequencing (LPS) that resulted in both nuclear DNA (nuDNA) and mitochondrial DNA (mtDNA) sequence reads. Mitochondrial DNA CN was estimated based on the ratio of mtDNA to nuDNA coverages. Genetic parameters for mtDNA CN were estimated from an animal model based on a genomic relationship matrix (~87K SNP from the nuDNA). Different models were used to test the effects of tissue, sex, age at sample collection, heterosis, and breed composition. Maternal effects, assessed by fitting a maternal additive component and by fitting eleven SNP on the mtDNA, were also obtained. As previously reported, mtDNA haplotypes were used to classify individuals into Taurine haplogroups (T1, T2, T3/T4, and T5). Estimates of heritability when fitting fixed effects in addition to the intercept were moderate, ranging from 0.11 to 0.31 depending on the model. From a model ignoring contemporary group, semen samples had the lowest mtDNA CN, as expected, followed by blood and leucocyte samples (P ≤ 0.001). The effect of sex and the linear and quadratic effects of age were significant (P ≤ 0.02) depending on the model. When significant, females had greater mtDNA CN than males. The effects of heterosis and maternal heterosis were not significant (P ≥ 0.47). The estimates of maternal and mtDNA heritability were near zero (≤0.03). Most of the samples (98%) were classified as haplogroup T3. Variation was observed in the mtDNA within Taurine haplogroups, which enabled the identification of 24 haplotypes. These results suggest that mtDNA CN is under nuclear genetic control and would respond favorably to selection.

Mitochondrial DNA copy number (mtDNA CN) is related to mitochondrial function and thus may be indicative of energy efficiency. This study investigated the genetic and non-genetic factors associated with mtDNA CN in a beef cattle population of 2,371 animals using whole-genome sequencing at low depth. Blood, leucocyte, and semen samples were subjected to whole-genome sequencing, resulting in mtDNA and nuclear DNA to estimate mtDNA CN. Findings revealed that 11% to 31% of the variation in mtDNA CN is under genetic control. Non-genetic effects of tissue type, age, and sex were significantly associated with mtDNA CN. Semen samples had the lowest mtDNA CN, followed by blood and leucocyte samples. Younger and older ages were associated with a greater mtDNA CN than intermediate ages. Females had greater mtDNA CN than males. Heterosis and breed composition were not significantly associated with mtDNA CN. These results suggest that mtDNA CN is heritable and would respond favorably to genetic selection.

Imputation of non-genotyped F1 dams to improve genetic gain in swine crossbreeding programs.

This study investigated using imputed genotypes from non-genotyped animals which were not in the pedigree for the purpose of genetic selection and improving genetic gain for economically relevant traits. Simulations were used to mimic a 3-breed crossbreeding system that resembled a modern swine breeding scheme. The simulation consisted of three purebred (PB) breeds A, B, and C each with 25 and 425 mating males and females, respectively. Males from A and females from B were crossed to produce AB females (n = 1,000), which were crossed with males from C to produce crossbreds (CB; n = 10,000). The genome consisted of three chromosomes with 300 quantitative trait loci and ~9,000 markers. Lowly heritable reproductive traits were simulated for A, B, and AB (h2 = 0.2, 0.2, and 0.15, respectively), whereas a moderately heritable carcass trait was simulated for C (h2 = 0.4). Genetic correlations between reproductive traits in A, B, and AB were moderate (rg = 0.65). The goal trait of the breeding program was AB performance. Selection was practiced for four generations where AB and CB animals were first produced in generations 1 and 2, respectively. Non-genotyped AB dams were imputed using FImpute beginning in generation 2. Genotypes of PB and CB were used for imputation. Imputation strategies differed by three factors: 1) AB progeny genotyped per generation (2, 3, 4, or 6), 2) known or unknown mates of AB dams, and 3) genotyping rate of females from breeds A and B (0% or 100%). PB selection candidates from A and B were selected using estimated breeding values for AB performance, whereas candidates from C were selected by phenotype. Response to selection using imputed genotypes of non-genotyped animals was then compared to the scenarios where true AB genotypes (trueGeno) or no AB genotypes/phenotypes (noGeno) were used in genetic evaluations. The simulation was replicated 20 times. The average increase in genotype concordance between unknown and known sire imputation strategies was 0.22. Genotype concordance increased as the number of genotyped CB increased with little additional gain beyond 9 progeny. When mates of AB were known and more than 4 progeny were genotyped per generation, the phenotypic response in AB did not differ (P > 0.05) from trueGeno yet was greater (P < 0.05) than noGeno. Imputed genotypes of non-genotyped animals can be used to increase performance when 4 or more progeny are genotyped and sire pedigrees of CB animals are known.

In swine breeding, phenotypic information is often gathered from elite purebred (PB) breeding stock and occasionally terminal crossbred animals (CB). Using economically relevant traits expressed by dams of CB (F1) in genetic evaluations is not common due to the lack of pedigree and/or genomic relationships to relate phenotypes of F1 to PB selection candidates. Since swine often have large litters, this study aimed to develop strategies to incorporate phenotypes of F1 into genetic evaluations by imputing F1 genotypes. Using simulation, we investigated the impact of CB pedigree completeness, the number of CB genotyped progeny, the number of parities (and thus mates) a F1 had, and genomic diversity in PB breeds on imputation accuracy and the response to selection in F1 performance. When mates of F1 were in the pedigree and 4 or more CB progeny were genotyped per generation, imputation accuracy was high and the phenotypic response in F1 did not differ compared to when true F1 genotypes were used. Our results show that imputed genotypes can be used to increase performance in swine breeding programs, but the magnitude depends upon the number of CB progeny genotyped, the number of F1 mates, and the completeness of the pedigree.

Genetic parameters, heterosis, and breed effects for body condition score and mature cow weight in beef cattle.

Understanding the genetic relationship between mature cow weight (MWT) and body condition score (BCS) is useful to implement selection programs focused on cow efficiency. The objectives of this study were to estimate genetic parameters, heterosis, and breed effects for MWT and BCS. In total, 25,035 and 24,522 overlapping records were available for MWT and BCS on 6,138 and 6,131 cows, respectively, from the Germplasm Evaluation program, a crossbred beef population at the U.S. Meat Animal Research Center. Pedigree was available for 48,013 individuals. Univariate animal models were used to estimate heritabilities for each trait by parity. Bivariate animal models were used to estimate genetic correlations between parities within a trait and between traits within parities. Bivariate repeatability animal models were used to estimate genetic correlations between traits across parities. Estimates of heritability for different parities ranged from 0.43 ±â€…0.05 to 0.55 ±â€…0.07 for MWT and from 0.12 ±â€…0.03 to 0.25 ±â€…0.04 for BCS and were lower with the repeatability model at 0.40 ±â€…0.02 and 0.11 ±â€…0.01 for MWT and BCS, respectively. Estimates of repeatability were high for MWT (0.67 ±â€…0.005) and low for BCS (0.22 ±â€…0.006). Estimates of genetic correlation for MWT and BCS between parities were, in general, high, especially between consecutive parities. Estimates of genetic correlation between MWT and BCS were positive and moderate, ranging from 0.32 ±â€…0.09 to 0.68 ±â€…0.14. The direct heterosis estimates were 21.56 ±â€…3.53 kg (P ≤ 0.001) for MWT and 0.095 ±â€…0.034 (P ≤ 0.001) for BCS. Ordered by decreasing MWT, the breeds ranked Brahman, Charolais, Angus, Simmental, Salers, Hereford, Santa Gertrudis, Chiangus, Brangus, Red Angus, Shorthorn, Maine-Anjou, Gelbvieh, Beefmaster, Limousin, and Braunvieh. Ordered by decreasing BCS, the breeds ranked Brahman, Red Angus, Charolais, Angus, Hereford, Brangus, Beefmaster, Chiangus, Salers, Simmental, Maine-Anjou, Limousin, Santa Gertrudis, Shorthorn, Gelbvieh, and Braunvieh. Estimates of breed differences for MWT were also adjusted for BCS (AMWT), and in general, AMWT depicted smaller differences between breeds with some degree of re-ranking (r = 0.59). These results suggest that MWT and BCS are at least moderately genetically correlated and that they would respond favorably to selection. Estimates of breed differences and heterotic effects could be used to parameterize multibreed genetic evaluations for indicators of cow maintenance energy requirements.

The current study estimated the genetic relationship between mature cow weight (MWT) and body condition score (BCS), heterosis, and breed effects for these traits in a crossbred beef population. In total, 25,035 and 24,522 overlapping records were available for MWT and BCS, respectively. Pedigree was available for 48,013 individuals. Heritability and genetic correlations were estimated within a trait between parities, between traits within parities, and between traits across parities. Estimates of heritability ranged from 0.40 ±â€…0.02 to 0.55 ±â€…0.07 for MWT and from 0.11 ±â€…0.01 to 0.25 ±â€…0.04 for BCS. Genetic correlations within a trait and between parities were, in general, high. Estimates of genetic correlation between MWT and BCS were positive and moderate, ranging from 0.32 ±â€…0.09 to 0.68 ±â€…0.14. Heterosis effects were 21.56 ±â€…3.53 kg for MWT and 0.095 ±â€…0.034 for BCS. For both traits, Brahman and Braunvieh were associated with the highest and lowest breed effects, respectively. These results suggest that MWT and BCS would respond favorably to selection and are moderately genetically correlated. Breed differences and heterotic effects could be used to parameterize multibreed genetic evaluations for indicators of cow maintenance energy requirements.

Bias in variance component estimation in swine crossbreeding schemes using selective genotyping and phenotyping strategies.

Selective genotyping of crossbred (CB) animals to include in traditionally purebred (PB) dominated genetic evaluations has been shown to provide an increase in the response to selection for CB performance. However, the inclusion of phenotypes from selectively genotyped CB animals, without the phenotypes of their non-genotyped cohorts, could cause bias in estimated variance components (VC) and subsequent estimated breeding values (EBV). The objective of the study was to determine the impact of selective CB genotyping on VC estimates and subsequent bias in EBV when non-genotyped CB animals are not included in genetic evaluations. A swine crossbreeding scheme producing 3-way CB animals was simulated to create selectively genotyped datasets. The breeding scheme consisted of three PB breeds each with 25 males and 450 females, F1 crosses with 1200 females and 12,000 CB progeny. Eighteen chromosomes each with 100 QTL and 4k SNP markers were simulated. Both PB and CB performances were considered to be moderately heritable (h2 = 0.4). Factors evaluated were as follows: 1) CB phenotype and genotype inclusion of 15% (n = 1800) or 35% (n = 4200), 2) genetic correlation between PB and CB performance (rpc = 0.1, 0.5, or 0.7), and 3) selective genotyping strategy. Genotyping strategies included the following: 1) Random: random CB selection, 2) Top: highest CB phenotype, and 3) Extreme: half highest and half lowest CB phenotypes. Top and Extreme selective genotyping strategies were considered by selecting animals in full-sib (FS) families or among the CB population (T). In each generation, 4320 PB selection candidates contributed phenotypic and genotypic records. Each scenario was replicated 15 times. VC were estimated for PB and CB performance utilizing bivariate models using pedigree relationships with dams of CB animals considered to be unknown. Estimated values of VC for PB performance were not statistically different from true values. Top selective genotyping strategies produced deflated estimates of phenotypic VC for CB performance compared to true values. When using estimated VC, Top_T and Extreme_T produced the most biased EBV, yet EBV of PB selection candidates for CB performance were most accurate when using Extreme_T. Results suggest that randomly selecting CB animals to genotype or selectively genotyping Top or Extreme CB animals within full-sib families can lead to accurate estimates of additive genetic VC for CB performance and unbiased EBV.

Genetic parameter estimates for bull prolificacy and its relationship with scrotal circumference in a commercial beef cattle population.

The commercial beef cattle industry relies heavily on the use of natural service sires. When artificial insemination is deemed difficult to implement, multisire breeding pastures are used to increase reproductive rates in large breeding herds or to safe-guard against bull injury during the breeding season. Although each bull might be given an equal opportunity to produce offspring, evidence suggest that there is substantial variation in the number of calves sired by each bull in a breeding pasture. With the use of DNA-based paternity testing, correctly assigning calves to their respective sires in multisire pastures is possible and presents an opportunity to investigate the degree to which this trait complex is under genetic control. Field data from a large commercial ranch was used to estimate genetic parameters for calf count (CC; 574 records from 443 sires) and yearling scrotal circumference (SC; n = 1961) using univariate and bivariate animal models. Calf counts averaged 12.2 ± 10.7 and SC averaged 35.4 ± 2.30 cm. Bulls had an average of 1.30 records and there were 23.9 ± 11.1 bulls per contemporary group. The model for CC included fixed effects of age during the breeding season (in years) and contemporary group (concatenation of breeding pasture and year). Random effects included additive genetic and permanent environmental effects, and a residual. The model for SC included fixed effects of age (in days) and contemporary group (concatenation of month and year of measurement). Random effects included an additive genetic effect and a residual. Univariate model heritability estimates for CC and SC were 0.178 ± 0.142 and 0.455 ± 0.072, respectively. Similarly, the bivariate model resulted in heritability estimates for CC and SC of 0.184 ± 0.142 and 0.457 ± 0.072, respectively. Repeatability estimates for CC from univariate and bivariate models were 0.315 ± 0.080 and 0.317 ± 0.080, respectively. The estimate of genetic correlation between CC and SC was 0.268 ± 0.274. Heritability estimates suggest that both CC and SC would respond favorably to selection. Moreover, CC is lowly repeatable and although favorably correlated, SC appears to be weakly associated with CC.

Breed and heterotic effects for mature weight in beef cattle.

Cow mature weight (MWT) is heritable and affects the costs and efficiency of a breeding operation. Cow weight is also influenced by the environment, and the relationship between the size and profitability of a cow varies depending on production system. Producers, therefore, need tools to incorporate MWT in their selection of cattle breeds and herd replacements. The objective of this study was to estimate breed and heterotic effects for MWT using weight-age data on crossbred cows. Cow's MWT at 6 yr was predicted from the estimated parameter values-asymptotic weight and maturation constant (k)-from the fit of the Brody function to their individual data. Values were obtained for 5,156 crossbred cows from the U.S. Meat Animal Research Center (USMARC) Germplasm Evaluation Program using 108,957 weight records collected from approximately weaning up to 6 yr of age. The cows were produced from crosses among 18 beef breeds. A bivariate animal model was fitted to the MWT and k obtained for each cow. The fixed effects were birth year-season contemporary group and covariates of direct and maternal breed fractions, direct and maternal heterosis, and age at final weighing. The random effects were direct additive and residual. A maternal additive random effect was also fitted for k. In a separate analysis from that used to estimate breed effects and (co)variances, cow MWT was regressed on sire yearling weight (YWT) Expected Progeny Differences by its addition as a covariate to the animal model fitted for MWT. That regression coefficient was then used to adjust breed solutions for sire selection in the USMARC herd. Direct heterosis was 15.3 ± 2.6 kg for MWT and 0.000118 ± 0.000029 d-1 for k. Maternal heterosis was -5.7 ± 3.0 kg for MWT and 0.000130 ± 0.000035 d-1 for k. Direct additive heritabilities were 0.56 ± 0.03 for MWT and 0.23 ± 0.03 for k. The maternal additive heritability for k was 0.11 ± 0.02. The direct additive correlation between MWT and k was negligible (0.08 ± 0.09). Adjusted for sire sampling, Angus was heaviest at maturity of the breeds compared. Deviations from Angus ranged from -8.9 kg (Charolais) to -136.7 kg (Braunvieh). Ordered by decreasing MWT, the breeds ranked Angus, Charolais, Hereford, Brahman, Salers, Santa Gertrudis, Simmental, Maine Anjou, Limousin, Red Angus, Brangus, Chiangus, Shorthorn, Gelbvieh, Beefmaster, and Braunvieh. These breed effects for MWT can inform breeding programs where cow size is considered a key component of the overall profitability.

Effects of management decisions on genetic evaluation of simulated calving records using random regression.

The objective of this study was to evaluate the effects of various data structures on the genetic evaluation for the binary phenotype of reproductive success. The data were simulated based on an existing pedigree and an underlying fertility phenotype with a heritability of 0.10. A data set of complete observations was generated for all cows. This data set was then modified mimicking the culling of cows when they first failed to reproduce, cows having a missing observation at either their second or fifth opportunity to reproduce as if they had been selected as donors for embryo transfer, and censoring records following the sixth opportunity to reproduce as in a cull-for-age strategy. The data were analyzed using a third-order polynomial random regression model. The EBV of interest for each animal was the sum of the age-specific EBV over the first 10 observations (reproductive success at ages 2-11). Thus, the EBV might be interpreted as the genetic expectation of number of calves produced when a female is given 10 opportunities to calve. Culling open cows resulted in the EBV for 3-yr-old cows being reduced from 8.27 ± 0.03 when open cows were retained to 7.60 ± 0.02 when they were culled. The magnitude of this effect decreased as cows grew older when they first failed to reproduce and were subsequently culled. Cows that did not fail over the 11 yr of simulated data had an EBV of 9.43 ± 0.01 and 9.35 ± 0.01 based on analyses of the complete data and the data in which cows that failed to reproduce were culled, respectively. Cows that had a missing observation for their second record had a significantly reduced EBV, but the corresponding effect at the fifth record was negligible. The current study illustrates that culling and management decisions, and particularly those that affect the beginning of the trajectory of sustained reproductive success, can influence both the magnitude and accuracy of resulting EBV.

Epigenetic clock and methylation study of oocytes from a bovine model of reproductive aging.

Cattle are an attractive animal model of fertility in women due to their high degree of similarity relative to follicle selection, embryo cleavage, blastocyst formation, and gestation length. To facilitate future studies of the epigenetic underpinnings of aging effects in the female reproductive axis, several DNA methylation-based biomarkers of aging (epigenetic clocks) for bovine oocytes are presented. One such clock was germane to only oocytes, while a dual-tissue clock was highly predictive of age in both oocytes and blood. Dual species clocks that apply to both humans and cattle were also developed and evaluated. These epigenetic clocks can be used to accurately estimate the biological age of oocytes. Both epigenetic clock studies and epigenome-wide association studies revealed that blood and oocytes differ substantially with respect to aging and the underlying epigenetic signatures that potentially influence the aging process. The rate of epigenetic aging was found to be slower in oocytes compared to blood; however, oocytes appeared to begin at an older epigenetic age. The epigenetic clocks for oocytes are expected to address questions in the field of reproductive aging, including the central question: how to slow aging of oocytes.

Categorization of birth weight phenotypes for inclusion in genetic evaluations using a deep neural network.

Birth weight (BW) serves as a valuable indicator of the economically relevant trait of calving ease (CE), and erroneous data collection for BW could impact genetic evaluations for CE. The objective of the current study was to evaluate the use of deep neural networks (DNNs) for classifying contemporary groups (CGs) based on the method used to generate BW phenotypes. CGs (n = 120,000,000) ranging between 10 and 250 animals were simulated assuming 12 data collection and CG formation scenarios that could impact CG phenotypic variance, including weights recorded with a digital scale (REAL), hoof tape (TAPE), erroneous data collection (DIRTY), and those that were fabricated (FAB). The performance of eight activation functions (AFs; ReLu, Sigmoid, Exponential, ReLu6, Softmax, Softplus, Leaky ReLu, and Tanh) was evaluated. Four hidden layers were used with seven different scenarios relative to the number of neurons. Simulations were replicated 10 times. In general, accuracy (proportion of correct predictions) across AF and numbers of neurons were similar, with mean correlations ranging between 0.91 and 0.99. The AF ReLu, Sigmoid, Exponential, and ReLu6 had the greatest consistency (mean pair-wise correlation among replicates) with an average correlation of greater than 0.85. Independent of the number of neurons used, the sigmoid function produced the highest accuracy (0.99) and consistency (0.93). The model with the greatest accuracy and consistency was then applied to real BW data supplied by the American Hereford Association. In the real data, the lowest phenotypic variance was for FAB CG (2.65 kg2), REAL CG had the largest (15.84 kg2), and TAPE CG was intermediate (6.84 kg2). To investigate the potential impact of FAB data on routine genetic evaluations, CGs classified as FAB in 90% or more of the replicates were removed from the evaluation for CE, and the rank of resulting genetic predictions were compared with the case where records were not removed. The removal of FAB CG had a moderate impact on the prediction of CE expected progeny differences, primarily for animals with intermediate to high accuracy. The results suggest that a well-trained DNN can be effectively used to classify data based on quality metrics prior to the inclusion in routine genetic evaluation.