Linkage disequilibrium among commonly genotyped SNP variants detected from bull sequence.

Genomic prediction utilizing causal variants could increase selection accuracy above that achieved with SNPs genotyped by currently available arrays used for genomic selection. A number of variants detected from sequencing influential sires are likely to be causal, but noticeable improvements in prediction accuracy using imputed sequence variant genotypes have not been reported. Improvement in accuracy of predicted breeding values may be limited by the accuracy of imputed sequence variants. Using genotypes of SNPs on a high-density array and non-synonymous SNPs detected in sequence from influential sires of a multibreed population, results of this examination suggest that linkage disequilibrium between non-synonymous and array SNPs may be insufficient for accurate imputation from the array to sequence. In contrast to 75% of array SNPs being strongly correlated to another SNP on the array, less than 25% of the non-synonymous SNPs were strongly correlated to an array SNP. When correlations between non-synonymous and array SNPs were strong, distances between the SNPs were greater than separation that might be expected based on linkage disequilibrium decay. Consistently near-perfect whole-genome linkage disequilibrium between the full array and each non-synonymous SNP within the sequenced bulls suggests that whole-genome approaches to infer sequence variants might be more accurate than imputation based on local haplotypes. Opportunity for strong linkage disequilibrium between sequence and array SNPs may be limited by discrepancies in allele frequency distributions, so investigating alternate genotyping approaches and panels providing greater chances of frequency-matched SNPs strongly correlated to sequence variants is also warranted. Genotypes used for this study are available from https://www.animalgenome.org/repository/pub/;USDA2017.0519/.

Estimates of epistatic and pleiotropic effects of () and () genetic markers on beef heifer performance traits enhanced by selection.

Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC II) was subjected to marker assisted selection for 2 yr to equalize and genetic marker frequencies to evaluate the epistatic and pleiotropic effects of these markers on BW, reproduction, and first calf performance traits in replacement beef females ( = 171) managed under 2 postweaning development protocols. Traits evaluated on the heifers were birth BW, weaning BW, 11-mo BW, 12-mo BW, 13-mo BW, first breeding season pregnancy evaluation BW, first calving season BW, 11-mo puberty, 12-mo puberty, 13-mo puberty, first breeding season pregnancy, and first calf weaning rate. Additionally, heifer's first calf performance traits of ordinal calving date, first calf birth BW, and first calf weaning BW (with and without age adjustment) were analyzed. Selection to increase minor allele frequencies and balanced sampling across genotype classes enhanced the ability to detect all genetic effects except dominance × dominance epistasis. The × genotype effect was significant ( < 0.05) for 11-mo BW and 12-mo BW and tended to be significant ( = 0.08) for 13-mo BW. Consistently, for all 3 traits, the most significant effect among epistatic × genotype effects was the additive effect, with the G allele decreasing BW. There were no associations between × genotype and fertility related traits ( ≥ 0.46) in this study. Additionally, there were no × genotype associations with first progeny performance traits ( ≥ 0.14). The large effect of the additive × additive interaction on first calf weaning BW was imprecisely estimated, which may warrant further investigation.

A survey of polymorphisms detected from sequences of popular beef breeds.

The genome sequence was obtained from 270 sires used in the Germplasm Evaluation (GPE) project. These bulls included 154 purebred AI sires from GPE Cycle VII breeds (Hereford, Angus, Simmental, Limousin, Charolais, Gelbvieh, and Red Angus), 83 F crosses of those breeds, and 33 AI sires from 8 other breeds. The exome capture sequence targeting coding regions of the genome was obtained from 176 of these bulls. Sequence reads were mapped to the UMD 3.1 bovine genome assembly; a mean of 2.5-fold (x) coverage per bull was obtained from the genomic sequence, and the targeted exons were covered at a mean of 20.0x. Over 28.8 million biallelic sequence variants were detected where each allele was present in at least 3 different bulls. These included 22.0 million previously reported variants and 94.1% of the 774,660 autosomal and BTA X SNP on the BovineHD BeadChip assay (HD). More than 92% of the variants detected in targeted exons were also detected from the low-coverage genome sequence. Less than 1% of the variants detected from the combined genome and exome sequence occurred in annotated protein-coding sequences and 5' and 3' untranslated regions (UTR) surrounding the 19,994 annotated protein coding regions. Variation was detected in the coding sequence or UTR of 96.8% of the genes: loss-of-function variants were predicted for 3,298 genes, 14,973 contained nonsynonymous variants, 11,276 had variation in UTR, and 17,721 genes contained synonymous variants. Minor allele frequencies (MAF) were <0.05 for 47.8% of the coding sequence and UTR variants, and MAF distributions were skewed toward low MAF. In contrast, 11.1% of the HD SNP detected in these bulls had MAF < 0.05, and the distribution was skewed toward higher MAF. Genes involved in immune system processes and immune response were overrepresented among those genes containing high MAF loss-of-function and nonsynonymous polymorphisms. Detected variants were submitted to the National Center for Biotechnology Information genetic variation database (dbSNP) under the handle MARC, batch GPE_Bull_GenEx.

A polymorphism in myostatin influences puberty but not fertility in beef heifers, whereas µ-calpain affects first calf birth weight.

The use of genetic markers to aid in selection decisions to improve carcass and growth characteristics is of great interest to the beef industry. However, it is important to examine potential antagonistic interactions with fertility in cows before widespread application of marker-assisted selection. The objective of the current experiment was to examine the influence of 2 commercially available markers currently in use for improving carcass traits, the myostatin (MSTN) F94L and µ-calpain (CAPN1) 316 and 4751 polymorphisms, on heifer development and reproductive performance. In Exp. 1, beef heifers (n = 146) were evaluated for growth and reproductive traits over a 3-yr period to determine if these polymorphisms influenced reproductive performance. In Exp. 2, heifers representing the 2 homozygous genotypes for the MSTN F94L polymorphism were slaughtered on d 4 of the estrous cycle and reproductive tracts were collected for morphological examination. In Exp. 1, there was a tendency (P = 0.06) for birth BW to be affected by MSTN with the Leu allele increasing birth BW in an additive fashion. Additionally, MSTN significantly affected the proportion of pubertal heifers by the start of the breeding season (P < 0.05) with the Leu allele additively decreasing the proportion pubertal; however, this did not result in a delay in conception or a decrease in pregnancy rates during the first breeding season (P > 0.15). The GT haplotype of CAPN1, which was previously associated with decreased meat tenderness, was associated with an additive decrease in birth BW of the first calf born to these heifers (P < 0.05). In Exp. 2, there were no differences between the MSTN genotypes for gross or histological morphology of the anterior pituitary, uterus, or ovaries (P > 0.05). From these results, we concluded that the MSTN F94L and CAPN1 polymorphisms can be used to improve carcass traits without compromising fertility in beef heifers. The influence of these markers on cow performance and herd life remains to be determined. While the delay in puberty associated with the MSTN F94L polymorphism did not negatively impact reproductive performance in heifers, caution should be used when combining this marker with other markers for growth or carcass traits until the potential interactions are more clearly understood.

CAPN1, CAST, and DGAT1 genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in a beef cattle population selected for haplotype and allele equalization.

Genetic marker effects and type of inheritance are estimated with poor precision when minor marker allele frequencies are low. A stable composite population (MARC III) was subjected to marker-assisted selection for multiple years to equalize specific marker frequencies to 1) estimate effect size and mode of inheritance for previously reported SNP on targeted beef carcass quality traits (n=254), 2) estimate pleiotropic effects of previously reported SNP on nontarget performance traits (n=542 or 254), and 3) evaluate tenderness SNP specific residual variance for LM tenderness. Three haplotypes within µ-calpain (CAPN1), a SNP in calpastatin (CAST), and a dinucleotide substitution in diacylglycerol O-acyltransferase 1 (DGAT1) were successfully selected to equalize their frequencies. Traits evaluated were birth BW, weaning BW, yearling BW, final BW, dressing percent, HCW, fat thickness, LM area, USDA marbling score, yield grade, LM slice shear force (SSF), and visible and near-infrared (VISNIR)-predicted SSF. While the CAPN1 genotype effect on SSF was not significant (P=0.12), the direction and size of CAPN1 contrasts were consistent with previous research. Effects on SSF between divergent CAPN1 haplotypes (1.153 kg) and the additive effect of CAST (0.902 kg) were large, and animals homozygous for tender alleles at both CAPN1 and CAST would have 4.11 kg lower SSF (27.5% of the mean) than animals homozygous tough for both markers. Furthermore, the interaction between CAPN1 and CAST for SSF was not significant (P=0.40). There were significant effects for DGAT1 on adjusted fat thickness (P=0.02) and VISNIR-predicted SSF (P<0.001) with additive and dominance modes of inheritance (P<0.05) for both traits. Furthermore, CAST genotype specific residual variance models fit significantly better (P<0.001) than single residual variance models for SSF, with the tougher genotypes having progressively larger residual (and hence phenotypic) variances. Therefore, risk of a tough steak from the undesired CAST genotype is increased through both an increase in mean and an increase in variation. This work is supportive of the importance of CAPN1 and CAST for mean tenderness in beef, confirms an effect of CAST on beef LM tenderness variation, and identifies an effect of DGAT1 on subcutaneous fat thickness.

Performance of multidetector CT in the evaluation of the endometrium: Measurement of endometrial thickness and detection of disease.

AIM: To evaluate the performance of multidetector computed tomography (MDCT) in the measurement of endometrial thickness and assessment for endometrial disease. MATERIALS AND METHODS: Seventy-nine MDCT examinations, including sagittal reformats from isotropic data, were retrospectively evaluated for the presence of endometrial abnormality, endometrial thickness, and recommendation for transvaginal ultrasound (TVUS) after CT. The endometrial thickness was measured on sagittal images using two different methods, between the inner-to-inner hypoattenuating stripe, and when visible, between the outer-to-outer hyperattenuating stripe. TVUS performed within 48 h of CT in premenopausal and 1 month in postmenopausal patients served as reference standard. Interobserver agreement for endometrial thickness and abnormalities was assessed using concordance correlation (CC) and kappa statistics. RESULTS: Interobserver agreement for endometrial thickness on sagittal CT images was excellent (CC 0.98), and highly accurate using the inner-to-inner measurement. For determination of abnormal thickening, the positive predictive value and negative predictive value were 67-100% and 99.5-100%. For detection of any endometrial abnormality, the positive predictive value and negative predictive value were 79-90% and 84-95%, respectively. False-negative missed abnormalities included small volume hydrometra, a polyp, and endometrial distortion by a fibroid. CONCLUSION: At MDCT, sagittal reformatted images provide reliable endometrial measurement using the inner-to-inner hypoattenuating stripe and are accurately categorized as normal or abnormal thickness using the same numerical criteria as at sonography.

µ-Calpain, calpastatin, and growth hormone receptor genetic effects on preweaning performance, carcass quality traits, and residual variance of tenderness in Angus cattle selected to increase minor haplotype and allele frequencies.

Genetic marker effects and interactions are estimated with poor precision when minor marker allele frequencies are low. An Angus population was subjected to marker assisted selection for multiple years to increase divergent haplotype and minor marker allele frequencies to 1) estimate effect size and mode of inheritance for previously reported SNP on targeted beef carcass quality traits; 2) estimate effects of previously reported SNP on nontarget performance traits; and 3) evaluate tenderness SNP specific residual variance models compared to a single residual variance model for tenderness. Divergent haplotypes within µ-calpain (CAPN1), and SNP within calpastatin (CAST) and growth hormone receptor (GHR) were successfully selected to increase their frequencies. Traits evaluated were birth BW, weaning BW, final BW, fat thickness, LM area, USDA marbling score, yield grade, slice shear force (SSF), and visible and near infrared predicted slice shear force. Both CAPN1 and CAST exhibited additive (P < 0.001) modes of inheritance for SSF and neither exhibited dominance (P ≥ 0.19). Furthermore, the interaction between CAPN1 and CAST for SSF was not significant (P = 0.55). Estimated additive effects of CAPN1 (1.049 kg) and CAST (1.257 kg) on SSF were large in this study. Animals homozygous for tender alleles at both CAPN1 and CAST would have 4.61 kg lower SSF (38.6% of the mean) than animals homozygous tough for both markers. There was also an effect of CAST on yield grade (P < 0.02). The tender CAST allele was associated with more red meat yield and less trimmable fat. There were no significant effects (P ≥ 0.23) for GHR on any of the traits evaluated in this study. Furthermore, CAST specific residual variance models were found to fit significantly better (P < 0.001) than single residual variance models for SSF, with the tougher genotypes having larger residual variance. Thus, the risk of a tough steak from the undesired CAST genotype is increased through both an increase in mean and an increase in variation. This work confirms the importance of CAPN1 and CAST for tenderness in beef, provides a new effect of CAST on beef tenderness, and questions the utility of GHR as a selection marker for beef quality.

Prevalence of pelvic organ prolapse detected at dynamic MRI in women without history of pelvic floor dysfunction: comparison of two reference lines.

AIM: To retrospectively evaluate the prevalence of pelvic organ prolapse as an incidental finding on dynamic magnetic resonance imaging (MRI) using two different references lines. MATERIALS AND METHODS: Sixty women with symptoms unrelated to pelvic floor dysfunction who underwent MRI including a dynamic sagittal true fast imaging with steady-state free precession (TrueFISP) sequence during straining were identified. Two radiologists in consensus used the pubococcygeal line (PCL) and mid-pubic line (MPL) to diagnose and grade prolapse in all three pelvic compartments. RESULTS: Cystocele was absent, mild, moderate, and severe in 88% (53/60), 7% (4/60), 5% (3/60), and 0% (0/60) of patients, respectively, using PCL, versus 78% (47/60), 13% (8/60), 5% (3/60), and 3% (2/60) of patients, respectively, using MPL. Vaginal prolapse was absent, mild, moderate, and severe in 95% (57/60), 5% (3/60), 0% (0/60), and 0% (0/60) of patients, respectively, using PCL, versus 80% (48/60), 17% (10/60), 3% (2/60), and 0% (0/60) of patients, respectively, using MPL. Rectal descent was absent, mild, moderate, and severe in 63% (38/60), 10% (6/60), 23% (14/60), and 3% (2/60) of patients, respectively, using PCL, versus 43% (26/60), 27% (16/60), 27% (16/60), and 3% (2/60) of patients, respectively, using MPL. No enterocele, peritoneocele, or muscular defect was identified. Two percent (1/60) of patients had mild rectocele, 8% (5/60) had abnormal vesico-urethral angle, and 25% (15/60) had abnormal levator plate angle. CONCLUSION: In asymptomatic women, dynamic MRI identified the greatest degrees of prolapse in the posterior compartment. The MPL consistently yielded greater frequency of prolapse than the PCL. Findings of pelvic organ prolapse may be observed in asymptomatic patients and are of uncertain significance, requiring correlation with clinical and physical examination findings.

The change in differing leukocyte populations during vaccination to bovine respiratory disease and their correlations with lung scores, health records, and average daily gain.

Bovine respiratory disease (BRD) is the most economically important disease in U.S. feedlots. Infection can result in morbidity, mortality, and reduced average daily gain. Cheap and reliable genetic methods of prediction and protection from BRD would be highly advantageous to the industry. The immune response may correlate with BRD incidence. Cattle (n = 2,182) were vaccinated against common viral and bacterial pathogens of BRD. Two blood samples were collected, one during booster vaccination and one 21d later, enabling 3 phenotypes for each trait [prebooster (pre), postbooster (post), and delta (post minus pre)]. From the blood samples innate and adaptive responses [counts of white blood cells (WBC), neutrophils, lymphocytes, monocytes, eosinophils, and basophils] were measured. In addition, feedlot ADG and binary traits [health records (HR; 0 = healthy, 1 = ill) and lung scores (LS; collected at harvest; 0 = no lesions, 1 = lesions)] were also recorded. Traits ADG, HR, and LS have all been significantly correlated with infection to BRD. In this investigation we aimed to find correlations between the immune response and ADG, HR, and LS to find an easily measurable trait that would be a good predictor of BRD resistance after vaccination. The results showed an average positive delta for the innate immune response (eosinophils, basophils, neutrophils), whereas the adaptive immune response had an average negative delta (lymphocytes). Overall, we discovered that the immune responses had moderately high heritabilities (h(2); lowest: delta monocytes, 0.21 ± 0.05; greatest: pre lymphocytes: 0.5 ± 0.05), with lymphocytes having the greatest h(2) throughout the study (h(2) ≥ 0.41). All genetic correlations were calculated using bivariate REML models. Although LS did not significantly correlate with any of the immune phenotypes, both ADG (post lymphocytes, -0.24 ± 0.12) and HR (pre eosinophils, -0.67 ± 0.29; delta WBC, -0.5 ± 0.24, and delta lymphocytes, -0.67 ± 0.21) did. All the significant genetic correlations with HR were negative; resistance to BRD appears to be a function of greater delta lymphocytes and WBC. The increase in eosinophils may potentially link its role in decreasing lymphocytes. These results may enable producers to predict if revaccination, quarantine, and breeding of animals is required to reduce the incidence of BRD postvaccination. In addition, immunological phenotypes maybe used to aid genomic selection indices to select animals with greater rates of protection after BRD vaccination.

A genomewide association study identified CYP2J2 as a gene controlling serum vitamin D status in beef cattle.

Vitamin D is an important modulator of calcium homeostasis and has several effects on the immune system. The objective of the study was to estimate its heritability and to identify genomic regions associated with concentration of circulating 25-hydroxyvitamin D (25OHD) in beef cattle. Status of vitamin D was measured in crossbred animals from Cycle VII of the United States Meat Animal Research Center (USMARC) Germplasm Evaluation Project. Progeny were born from March through May in 2008 and in 2010. Heritability was estimated and a genomewide association study was conducted on the concentration of 25OHD measured in 1,432 animals at preconditioning and 1,333 animals at weaning. Genotyping of the population was done by imputing from the parental generation genotyped with a high density array (777,000 SNP) to a target population genotyped with a medium density SNP array (50,000 SNP). After imputation, 675,018 SNP were used in the genomewide association study. Heritability of concentration of circulating 25OHD in cattle at preconditioning and at weaning was 0.41 ± 0.08 and 0.32 ± 0.11, respectively. A region on chromosome 3 was associated with circulating 25OHD. The region on BTA3 had 7 SNP significantly (P < 7.4 × 10(-8)) associated at the genomewide level with serum concentrations of serum 25OHD. Genomewide significant SNP spanned the region between 84.93 and 86.65 megabases (Mb); however, 6 SNP reside between 86.64 and 86.65 Mb. The gene CYP2J2 was identified as a candidate gene associated with concentrations of serum 25OHD in cattle. This is 1 of 6 enzymes involved in metabolizing vitamin D to 25OHD. Results from the present study suggest that CYP2J2 is a gene controlling serum 25OHD concentrations in cattle. CYP2J2 should be considered a prime candidate for understanding both genetic and physiological factors affecting serum 25OHD concentrations in cattle and, therefore, vitamin D status.

Selection for genetic markers in beef cattle reveals complex associations of thyroglobulin and casein1-s1 with carcass and meat traits.

Genetic markers in casein (CSN1S1) and thyroglobulin (TG) genes have previously been associated with fat distribution in cattle. Determining the nature of these genetic associations (additive, recessive, or dominant) has been difficult, because both markers have small minor allele frequencies in most beef cattle populations. This results in few animals homozygous for the minor alleles. selection to increase the frequencies of the minor alleles for 2 SNP markers in these genes was undertaken in a composite population. The objective was to obtain better estimates of genetic effects associated with these markers and determine if there were epistatic interactions. Selection increased the frequencies of minor alleles for both SNP from <0.30 to 0.45. Bulls (n = 24) heterozygous for both SNP were used in 3 yr to produce 204 steer progeny harvested at an average age of 474 d. The combined effect of the 9 CSN1S1 × TG genotypes was associated with carcass-adjusted fat thickness (P < 0.06) and meat tenderness predicted at the abattoir by visible and near-infrared reflectance spectroscopy (P < 0.04). Genotype did not affect BW from birth through harvest, ribeye area, marbling score, slice shear force, or image-based yield grade (P > 0.10). Additive, dominance, and epistatic SNP association effects were estimated from genotypic effects for adjusted fat thickness and predicted meat tenderness. Adjusted fat thickness showed a dominance association with TG SNP (P < 0.06) and an epistatic additive CSN1S1 × additive TG association (P < 0.03). For predicted meat tenderness, heterozygous TG meat was more tender than meat from either homozygote (P < 0.002). Dominance and epistatic associations can result in different SNP allele substitution effects in populations where SNP have the same linkage disequilibrium with causal mutations but have different frequencies. Although the complex associations estimated in this study would contribute little to within-population selection response, they could be important for marker-assisted management or reciprocal selection schemes.

Accuracy of genomic breeding values in multibreed beef cattle populations derived from deregressed breeding values and phenotypes.

Genomic selection involves the assessment of genetic merit through prediction equations that allocate genetic variation with dense marker genotypes. It has the potential to provide accurate breeding values for selection candidates at an early age and facilitate selection for expensive or difficult to measure traits. Accurate across-breed prediction would allow genomic selection to be applied on a larger scale in the beef industry, but the limited availability of large populations for the development of prediction equations has delayed researchers from providing genomic predictions that are accurate across multiple beef breeds. In this study, the accuracy of genomic predictions for 6 growth and carcass traits were derived and evaluated using 2 multibreed beef cattle populations: 3,358 crossbred cattle of the U.S. Meat Animal Research Center Germplasm Evaluation Program (USMARC_GPE) and 1,834 high accuracy bull sires of the 2,000 Bull Project (2000_BULL) representing influential breeds in the U.S. beef cattle industry. The 2000_BULL EPD were deregressed, scaled, and weighted to adjust for between- and within-breed heterogeneous variance before use in training and validation. Molecular breeding values (MBV) trained in each multibreed population and in Angus and Hereford purebred sires of 2000_BULL were derived using the GenSel BayesCπ function (Fernando and Garrick, 2009) and cross-validated. Less than 10% of large effect loci were shared between prediction equations trained on (USMARC_GPE) relative to 2000_BULL although locus effects were moderately to highly correlated for most traits and the traits themselves were highly correlated between populations. Prediction of MBV accuracy was low and variable between populations. For growth traits, MBV accounted for up to 18% of genetic variation in a pooled, multibreed analysis and up to 28% in single breeds. For carcass traits, MBV explained up to 8% of genetic variation in a pooled, multibreed analysis and up to 42% in single breeds. Prediction equations trained in multibreed populations were more accurate for Angus and Hereford subpopulations because those were the breeds most highly represented in the training populations. Accuracies were less for prediction equations trained in a single breed due to the smaller number of records derived from a single breed in the training populations.

Physiology and Endocrinology Symposium: How single nucleotide polymorphism chips will advance our knowledge of factors controlling puberty and aid in selecting replacement beef females.

The promise of genomic selection is accurate prediction of the genetic potential of animals from their genotypes. Simple DNA tests might replace low-accuracy predictions for expensive or lowly heritable measures of puberty and fertility based on performance and pedigree. Knowing with some certainty which DNA variants (e.g., SNP) affect puberty and fertility is the best way to fulfill the promise. Several SNP from the BovineSNP50 assay have tentatively been associated with reproductive traits including age at puberty, antral follicle count, and pregnancy observed on different sets of heifers. However, sample sizes are too small and SNP density is too sparse to definitively determine genomic regions harboring causal variants affecting reproductive success. Additionally, associations between individual SNP and similar phenotypes are inconsistent across data sets, and genomic predictions do not appear to be globally applicable to cattle of different breeds. Discrepancies may be a result of different QTL segregating in the sampled populations, differences in linkage disequilibrium (LD) patterns such that the same SNP are not correlated with the same QTL, and spurious correlations with phenotype. Several approaches can be used independently or in combination to improve detection of genomic factors affecting heifer puberty and fertility. Larger samples and denser SNP will increase power to detect real associations with SNP having more consistent LD with underlying QTL. Meta-analysis combining results from different studies can also be used to effectively increase sample size. High-density genotyping with heifers pooled by pregnancy status or early and late puberty can be a cost-effective means to sample large numbers. Networks of genes, implicated by associations with multiple traits correlated with puberty and fertility, could provide insight into the complex nature of these traits, especially if corroborated by functional annotation, established gene interaction pathways, and transcript expression. Example analyses are provided to demonstrate how integrating information about gene function and regulation with statistical associations from whole-genome SNP genotyping assays might enhance knowledge of genomic mechanisms affecting puberty and fertility, enabling reliable DNA tests to guide heifer selection decisions.

Partial-genome evaluation of postweaning feed intake and efficiency of crossbred beef cattle.

The effects of individual SNP and the variation explained by sets of SNP associated with DMI, metabolic midtest BW, BW gain, and feed efficiency, expressed as phenotypic and genetic residual feed intake, were estimated from BW and the individual feed intake of 1,159 steers on dry lot offered a 3.0 Mcal/kg ration for at least 119 d before slaughter. Parents of these F(1) × F(1) (F(1)(2)) steers were AI-sired F(1) progeny of Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental bulls mated to US Meat Animal Research Center Angus, Hereford, and MARC III composite females. Steers were genotyped with the BovineSNP50 BeadChip assay (Illumina Inc., San Diego, CA). Effects of 44,163 SNP having minor allele frequencies >0.05 in the F(1)(2) generation were estimated with a mixed model that included genotype, breed composition, heterosis, age of dam, and slaughter date contemporary groups as fixed effects, and a random additive genetic effect with recorded pedigree relationships among animals. Variance in this population attributable to sets of SNP was estimated with models that partitioned the additive genetic effect into a polygenic component attributable to pedigree relationships and a genotypic component attributable to genotypic relationships. The sets of SNP evaluated were the full set of 44,163 SNP and subsets containing 6 to 40,000 SNP selected according to association with phenotype. Ninety SNP were strongly associated (P < 0.0001) with at least 1 efficiency or component trait; these 90 accounted for 28 to 46% of the total additive genetic variance of each trait. Trait-specific sets containing 96 SNP having the strongest associations with each trait explained 50 to 87% of additive variance for that trait. Expected accuracy of steer breeding values predicted with pedigree and genotypic relationships exceeded the accuracy of their sires predicted without genotypic information, although gains in accuracy were not sufficient to encourage that performance testing be replaced by genotyping and genomic evaluations.

Predicting breed composition using breed frequencies of 50,000 markers from the US Meat Animal Research Center 2,000 Bull Project.

Knowledge of breed composition can be useful in multiple aspects of cattle production, and can be critical for analyzing the results of whole genome-wide association studies currently being conducted around the world. We examine the feasibility and accuracy of using genotype data from the most prevalent bovine genome-wide association studies platform, the Illumina BovineSNP50 array (Illumina Inc., San Diego, CA), to estimate breed composition for individual breeds of cattle. First, allele frequencies (of Illumina-defined allele B) of SNP on the array for each of 16 beef cattle breeds were defined by genotyping a large set of more than 2,000 bulls selected in cooperation with the respective breed associations to be representative of their breed. With these breed-specific allele frequencies, the breed compositions of approximately 2,000 two-, three-, and four-way cross (of 8 breeds) cattle produced at the US Meat Animal Research Center were predicted by using a simple multiple regression technique or Mendel (http://www.genetics.ucla.edu/software/mendel) and their genotypes from the Illumina BovineSNP50 array, and were then compared with pedigree-based estimates of breed composition. The accuracy of marker-based breed composition estimates was 89% when using either estimation method for all breeds except Angus and Red Angus (averaged 79%), based on comparing estimates with pedigree-based average breed composition. Accuracy increased to approximately 88% when these 2 breeds were combined into an aggregate Angus group. Additionally, we used a subset of these markers, approximately 3,000 that populate the Illumina Bovine3K (Illumina Inc.), to see whether breed composition could be estimated with similar accuracy when using this reduced panel of SNP makers. When breed composition was estimated using only SNP in common with the Bovine 3K array, accuracy was slightly reduced to 83%. These results suggest that SNP data from these arrays could be used to estimate breed composition in most US beef cattle in situations where pedigree is not known (e.g., multiple-sire natural service matings, non-source-verified animals in feedlots or at slaughter). This approach can aid analyses that depend on knowledge of breed composition, including identification and adjustment of breed-based population stratification, when performing genome-wide association studies on populations with incomplete pedigrees. In addition, SNP-based breed composition estimates may facilitate fitting cow germplasm to the environment, managing cattle in the feedlot, and tracing disease cases back to the geographic region or farm of origin.

Genome-wide association study of growth in crossbred beef cattle.

Chromosomal regions harboring variation affecting cattle birth weight and BW gain to 1 yr of age were identified by marker association using the highly parallel BovineSNP50 BeadChip (50K) assay composed of 54,001 individual SNP. Genotypes were obtained from progeny (F(1); 590 steers) and 2-, 3-, and 4-breed cross grandprogeny (F(1)(2) = F(1) x F(1); 1,306 steers and 707 females) of 150 AI sires representing 7 breeds (22 sires per breed; Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental). Genotypes and birth, weaning, and yearling BW records were used in whole-genome association analyses to estimate effects of individual SNP on growth. Traits analyzed included growth component traits: birth weight (BWT), 205-d adjusted birth to weaning BW gain (WG), 160-d adjusted postweaning BW gain (PWG); cumulative traits: 205-d adjusted weaning weight (WW = BWT + WG) and 365-d adjusted yearling weight (YW = BWT + WG + PWG); and indexes of relative differences between postnatal growth and birth weight. Modeled fixed effects included additive effects of calf and dam SNP genotype, year-sex-management contemporary groups, and covariates for calf and dam breed composition and heterosis. Direct and maternal additive polygenic effects and maternal permanent environment effects were random. Missing genotypes, including 50K genotypes of most dams, were approximated with a single-locus BLUP procedure from pedigree relationships and known 50K genotypes. Various association criteria were applied: stringent tests to account for multiple testing but with limited power to detect associations with small effects, and relaxed nominal P that may detect SNP associated with small effects but include excessive false positive associations. Genomic locations of the 231 SNP meeting stringent criteria generally coincided with described previously QTL affecting growth traits. The 12,425 SNP satisfying relaxed tests were located throughout the genome. Most SNP associated with BWT and postnatal growth affected components in the same direction, although detection of SNP associated with one component independent of others presents a possible opportunity for SNP-assisted selection to increase postnatal growth relative to BWT.

Opportunities for collaborative phenotyping for disease resistance traits in a large beef cattle resource population.

The Germplasm Evaluation (GPE) Project at the US Meat Animal Research Center (USMARC) is planned to produce about 3,000 calves per year in support of the following objectives: identification and validation of genetic polymorphisms related to economically relevant traits (ERT), estimation of breed and heterosis effects among 16 breeds for ERT, and estimation of genetic correlations among ERT and physiological indicator traits (PIT). Opportunities exist for collaboration in the development and collection of PIT phenotypes for disease resistance. Other areas of potential collaboration include detailed diagnosis (identification of disease causing organisms, etc.) of treated animals, collaborative development of epidemiological statistical models that would extract more information from the records of diagnoses and treatments, or pharmacogenetics. Concentrating a variety of different phenotypes and research approaches on the same population makes each component much more valuable than it would be individually.

Experimental selection for calving ease and postnatal growth in seven cattle populations. I. Changes in estimated breeding values.

Selection was used to create select and control lines within 4 purebred and 3 composite cattle populations. Both lines were selected for similar direct yearling weight and maternal weaning weight EBV. Select lines were selected for lower 2-yr-old heifer calving difficulty score EBV and control lines were selected for average birth weight EBV. Select (n = 6,926) and control (n = 2,043) line calves were born from 1993 through 1999 and selection began with the 1992 mating. High replacement rates resulted in 2,188 births to select line and 598 births to control line heifers. Data used to calculate EBV came from these populations and from 15 yr of data preceding the experiment. Calving difficulty was scored from 1 (no assistance) to 7 (cesarean). Calving difficulty scores from all twins, malpresentations, and cows 3 yr old and older were eliminated. Except for the first year, when a single-trait BLUP was used, a multiple-trait BLUP was used to calculate direct and maternal EBV for calving difficulty score, birth weight, and weaning weight, and direct EBV for postweaning gain. Sires (n = 498) were selected from those born in both the preceding populations and the select and control lines. In purebred populations, some industry sires (n = 88) were introduced based on their EPD. Tests of mean select and control line EBV differences of calves born in the final 2 yr were based on population variation. Select line direct EBV were 1.06 lower for heifer calving difficulty score (P < 0.001) and 3.5 kg lower (P < 0.001) for birth weight than controls. Average differences for other EBV were small and not significant. Yearling weight EBV was intentionally increased in both select and control lines of purebred populations. Angus, Hereford, Charolais, and Gelbvieh yearling weight EBV in control lines increased by 32.4, 27.2, 21.0, and 10.5 kg, respectively, from 1991 and 1992 to 1998 and 1999 compared with an average increase of 2.7 kg in composite populations. Birth weight direct EBV in purebred control lines increased by approximately 8% of yearling weight EBV increases. Selection based on a multiple-trait BLUP was able to create lines differing in calving difficulty score and birth weight EBV, but not in weaning weight and postweaning gain EBV. Differences between lines should be useful for evaluating BLUP and other traits and for identifying potential limitations of genetically decreasing calving difficulty score and birth weight.

Experimental selection for calving ease and postnatal growth in seven cattle populations. II. Phenotypic differences.

Effects of selection for 2-yr-old heifer calving ease (reduced calving difficulty score) on phenotypic differences between select and control lines of cattle for birth, growth, yearling hip height, and pelvic measurements were estimated. The selection objective was to decrease calving difficulty score in 2-yr-old heifers, while either maintaining or increasing yearling weight. The control line objective was to maintain or increase yearling weight by the same amount as the select lines and to maintain or proportionally increase birth weight. Select and control lines were formed in 4 purebred and 3 composite populations. Selection began in 1992 and select (n = 6,926) and control (n = 2,043) line calves were born from 1993 through 1999. Selection was based on EBV calculated from a 4-trait BLUP with observations on 2-yr-old calving difficulty scores, birth weight, weaning weight, and postweaning gain. Calving difficulty was scored on a scale from 1 (unassisted) to 7 (caesarean). All birth traits in select lines differed significantly from control lines. Averaged over 7 yr, select lines calved 3.0 +/- 0.5 d earlier, had 1.8 +/- 0.5 d shorter gestations, were 2.99 +/- 0.32 kg lighter at birth, had 5.6 +/- 1.5% fewer calves assisted at birth (averaged across dam ages), and 2-yr-old heifers had 0.80 +/- 0.08 lower calving difficulty score. Select lines averaged 19.8% lower 2-yr-old heifer calving assistance, but there was no difference in calving assistance of older cows, resulting in a highly significant interaction of selection and dam classification. Preweaning ADG was increased 15 +/- 9 g/d (1.7%) in select lines. Increased preweaning gain offset decreased birth weights in select lines, resulting in weaning weights that did not differ (P = 0.71). Postweaning ADG (P = 0.16) and yearling weight (P = 0.41) also did not differ. Increased preweaning ADG in select lines was not maintained after weaning. Select line hip heights were 0.70 +/- 0.21 cm shorter when measured as yearlings. Pelvic height, width, and area of select heifers measured 25 to 74 d after yearling weights were not significantly different. The differences between select and control lines significantly changed over the course of the experiment for some traits. In the final 2 yr of the experiment, select lines had 3.9 kg lower birth weight and 1.3 cm shorter hip heights. Selection can be used effectively to reduce 2-yr-old calving difficulty and calving assistance while maintaining or increasing yearling weight.

Assessing the association of single nucleotide polymorphisms at the thyroglobulin gene with carcass traits in beef cattle.

The objective of this study was to assess the association of SNP in the thyroglobulin gene, including a previously reported marker in current industry use, with marbling score in beef cattle. Three populations, designated GPE6, GPE7, and GPE8, were studied. The GPE6 population sampled breeds that could be used as alternative germplasm sources in beef cattle production, including Wagyu, Swedish Red and White, Friesian, and Norwegian Red. The GPE7 population sampled 7 popular beef cattle breeds used in temperate climates of the United States: Angus, Charolais, Gelbvieh, Hereford, Limousin, Red Angus, and Simmental. The GPE8 population sampled Bos indicus-influenced breeds used in subtropical regions of the country and subtropical and tropical regions of the world, including Beefmaster, Bonsmara, Brangus, and Romosinuano. Evaluation of 6 SNP in the thyroglobulin gene, including 5 newly described variations, showed no association (P > 0.10) with marbling score in these populations, except a tendency (P < 0.10) for an association with the previously described marker in GPE6. Closer examination of the GPE6 data revealed that the source of the tendency was an association (P < 0.02) with marbling in animals of Wagyu inheritance. Animals having Wagyu background and inheriting the TT genotype had a greater marbling score (599 +/- 20) than those inheriting the CC (540 +/- 10) or the CT (541 +/- 11) genotype. No association was detected with any other carcass trait for this marker in the 3 populations. Furthermore, none of the 5 newly described markers in the gene displayed an association with marbling score. The data indicate that markers at the thyroglobulin gene may be a useful predictor of marbling performance for producers raising Wagyu-based cattle. Although associations with marbling score in the remaining populations were not large or significant, the TT genotype had the numerically greatest marbling score in each population.