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Background: Genome-wide association studies (GWAS) are a powerful tool for detecting genomic regions explaining variation in phenotype. The objectives of the present study were to identify or refine the positions of genomic regions affecting milk production, milk components and fertility traits in Canadian Holstein cattle, and to use these positions to identify genes and pathways that may influence these traits., Result: Several QTL regions were detected for milk production (MILK), fat production (FAT), protein production (PROT) and fat and protein deviation (FATD, PROTD respectively). The identified QTL regions for production traits (including milk production) support previous findings and some overlap with genes with known relevant biological functions identified in earlier studies such as DGAT1 and CPSF1. A significant region on chromosome 21 overlapping with the gene FAM181A and not previous linked to fertility in dairy cattle was identified for the calving to first service interval and days open. A functional enrichment analysis of the GWAS results yielded GO terms consistent with the specific phenotypes tested, for example GO terms GO:0007595 (lactation) and GO:0043627 (response to estrogen) for milk production (MILK), GO:0051057 (positive regulation of small GTPase mediated signal transduction) for fat production (FAT), GO:0040019 (positive regulation of embryonic development) for first service to calving interval (CTFS) and GO:0043268 (positive regulation of potassium ion transport) for days open (DO). In other cases the connection between the enriched GO terms and the traits were less clear, for example GO:0003279 (cardiac septum development) for FAT and GO:0030903 (notochord development) for DO trait., Conclusion: The chromosomal regions and enriched pathways identified in this study confirm several previous findings and highlight new regions and pathways that may contribute to variation in production or fertility traits in dairy cattle.

The accuracy of genomic predictions can be used to assess the utility of dense marker genotypes for genetic improvement of beef efficiency traits. This study was designed to test the impact of genomic distance between training and validation populations, training population size, statistical methods, and density of genetic markers on prediction accuracy for feed efficiency traits in multibreed and crossbred beef cattle. A total of 6,794 beef cattle data collated from various projects and research herds across Canada were used. Illumina BovineSNP50 (50K) and imputed Axiom Genome-Wide BOS 1 Array (HD) genotypes were available for all animals. The traits studied were DMI, ADG, and residual feed intake (RFI). Four validation groups of 150 animals each, including Angus (AN), Charolais (CH), Angus-Hereford crosses (ANHH), and a Charolais-based composite (TX) were created by considering the genomic distance between pairs of individuals in the validation groups. Each validation group had 7 corresponding training groups of increasing sizes ( = 1,000, 1,999, 2,999, 3,999, 4,999, 5,998, and 6,644), which also represent increasing average genomic distance between pairs of individuals in the training and validations groups. Prediction of genomic estimated breeding values (GEBV) was performed using genomic best linear unbiased prediction (GBLUP) and Bayesian method C (BayesC). The accuracy of genomic predictions was defined as the Pearson's correlation between adjusted phenotype and GEBV (), unless otherwise stated. Using 50K genotypes, the highest average achieved in purebreds (AN, CH) was 0.41 for DMI, 0.34 for ADG, and 0.35 for RFI, whereas in crossbreds (ANHH, TX) it was 0.38 for DMI, 0.21 for ADG, and 0.25 for RFI. Similarly, when imputed HD genotypes were applied in purebreds (AN, CH), the highest average was 0.14 for DMI, 0.15 for ADG, and 0.14 for RFI, whereas in crossbreds (ANHH, TX) it was 0.38 for DMI, 0.22 for ADG, and 0.24 for RFI. The of GBLUP predictions were greatly reduced with increasing genomic average distance compared to those from BayesC predictions. The results indicate that 50K genotypes, used with BayesC, are more effective for predicting GEBV in purebred cattle. Imputed HD genotypes found utility when dealing with composites and crossbreds. Formulation of a fairly large training set for genomic predictions in beef cattle should consider the genomic distance between the training and target populations.

Genomic selection is becoming a standard tool in livestock breeding programs, particularly for traits that are hard to measure. Accuracy of genomic selection can be improved by increasing the quantity and quality of data and potentially by improving analytical methods. Adding genotypes and phenotypes from additional breeds or crosses often improves the accuracy of genomic predictions but requires specific methodology. A model was developed to incorporate breed composition estimated from genotypes into genomic selection models. This method was applied to age at puberty data in female beef cattle (as estimated from age at first observation of a corpus luteum) from a mix of Brahman and Tropical Composite beef cattle. In this dataset, the new model incorporating breed composition did not increase the accuracy of genomic selection. However, the breeding values exhibited slightly less bias (as assessed by deviation of regression of phenotype on genomic breeding values from the expected value of 1). Adding additional Brahman animals to the Tropical Composite analysis increased the accuracy of genomic predictions and did not affect the accuracy of the Brahman predictions., (© 2015 Stichting International Foundation for Animal Genetics.)

Stenting treatments for the management of disease in the heart, arterial and venous systems, biliary ducts, urethras, ureters, oesophageal tract and prostate have made enormous technical advances since their introduction into clinical use. The progression from metallic to polymer based bio-absorbable stents, coupled with the advances in additive manufacturing techniques, present a unique opportunity to completely re-envision the design, manufacture, and supply chain of stents. This paper looks at current stenting trends and proposes a future where the stent supply chain is condensed from ~150 days to ~20 min. The Cardiologist therefore has the opportunity to become a designer, manufacturer and user with patients receiving custom stents specific to their unique pathology that will be generated, delivered and deployed in the Cath-lab. The paper will outline this potentially revolutionary development and consider the technical challenges that will need to be overcome in order to achieve these ambitious goals. A high level overview of the generating eluting stents in situ program-GENESIS-is outlined including some early experimental work.

Aim: Febrile urinary tract infections (UTIs) may be associated with long-term renal damage. Our goal was to identify risk factors for future UTIs in children who had voiding cystourethrography (VCUG) as a part of an antenatal hydronephrosis (ANH) assessment or after a febrile UTI., Methods: We conducted a cohort study based on the medical records of children aged 0-24 months who underwent a VCUG between January 2004 and December 2011 and had at least six months of follow-up. The incidence of future UTIs was assessed., Results: We included 285 children: 176 had a primary UTI and 109 had ANH. We recorded 28 UTIs during the follow-up period, and the risk was 12.5% after a primary UTI and 5.5% after an ANH (p = 0.049). Multivariate analysis showed no risk difference was found between the groups. Females had a greater risk of febrile UTIs (hazard ratio 3.3, 95% confidence interval 1.03-9.2, p = 0.04), but the UTI risk did not differ between children with or without VURs., Conclusion: Female infants were at greater risk of febrile UTIs, regardless of the presence of VUR, VUR degree, ANH or a previous UTI. Clinical guidelines for UTI and ANH assessment should preferably be gender specific., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Background: Whole genome sequences (WGS) have proliferated as sequencing technology continues to improve and costs decline. While many WGS of model or domestic organisms have been produced, a growing number of non-model species are also being sequenced. In the absence of a reference, construction of a genome sequence necessitates de novo assembly which may be beyond the ability of many labs due to the large volumes of raw sequence data and extensive bioinformatics required. In contrast, the presence of a reference WGS allows for alignment which is more tractable than assembly. Recent work has highlighted that the reference need not come from the same species, potentially enabling a wide array of species WGS to be constructed using cross-species alignment. Here we report on the creation a draft WGS from a single bighorn sheep (Ovis canadensis) using alignment to the closely related domestic sheep (Ovis aries)., Results: Two sequencing libraries on SOLiD platforms yielded over 865 million reads, and combined alignment to the domestic sheep reference resulted in a nearly complete sequence (95% coverage of the reference) at an average of 12x read depth (104 SD). From this we discovered over 15 million variants and annotated them relative to the domestic sheep reference. We then conducted an enrichment analysis of those SNPs showing fixed differences between the reference and sequenced individual and found significant differences in a number of gene ontology (GO) terms, including those associated with reproduction, muscle properties, and bone deposition., Conclusion: Our results demonstrate that cross-species alignment enables the creation of novel WGS for non-model organisms. The bighorn sheep WGS will provide a resource for future resequencing studies or comparative genomics.

Background: Previous genome-wide association analyses identified QTL regions in the X chromosome for percentage of normal sperm and scrotal circumference in Brahman and Tropical Composite cattle. These traits are important to be studied because they are indicators of male fertility and are correlated with female sexual precocity and reproductive longevity. The aim was to investigate candidate genes in these regions and to identify putative causative mutations that influence these traits. In addition, we tested the identified mutations for female fertility and growth traits., Results: Using a combination of bioinformatics and molecular assay technology, twelve non-synonymous SNPs in eleven genes were genotyped in a cattle population. Three and nine SNPs explained more than 1% of the additive genetic variance for percentage of normal sperm and scrotal circumference, respectively. The SNPs that had a major influence in percentage of normal sperm were mapped to LOC100138021 and TAF7L genes; and in TEX11 and AR genes for scrotal circumference. One SNP in TEX11 was explained ~13% of the additive genetic variance for scrotal circumference at 12 months. The tested SNP were also associated with weight measurements, but not with female fertility traits., Conclusions: The strong association of SNPs located in X chromosome genes with male fertility traits validates the QTL. The implicated genes became good candidates to be used for genetic evaluation, without detrimentally influencing female fertility traits.

Indicine cattle have lower reproductive performance in comparison to taurine. A chromosomal anomaly characterized by the presence Y markers in females was reported and associated with infertility in cattle. The aim of this study was to investigate the occurrence of the anomaly in Brahman cows. Brahman cows (n = 929) were genotyped for a Y chromosome specific region using real time-PCR. Only six out of 929 cows had the anomaly (0.6%). The anomaly frequency was much lower in Brahman cows than in the crossbred population, in which it was first detected. It also seems that the anomaly doesn't affect pregnancy in the population. Due to the low frequency, association analyses couldn't be executed. Further, SNP signal of the pseudoautosomal boundary region of the Y chromosome was investigated using HD SNP chip. Pooled DNA of "non-pregnant" and "pregnant" cows were compared and no difference in SNP allele frequency was observed. Results suggest that the anomaly had a very low frequency in this Australian Brahman population and had no effect on reproduction. Further studies comparing pregnant cows and cows that failed to conceive should be executed after better assembly and annotation of the Y chromosome in cattle.

Objective: Working within a series of partnerships among an academic health center, local health departments (LHDs), and faith-based organizations (FBOs), we validated companion interventions to address community mental health planning and response challenges in public health emergency preparedness., Methods: We implemented the project within the framework of an enhanced logic model and employed a multi-cohort, pre-test/post-test design to assess the outcomes of 1-day workshops in psychological first aid (PFA) and guided preparedness planning (GPP). The workshops were delivered to urban and rural communities in eastern and midwestern regions of the United States. Intervention effectiveness was based on changes in relevant knowledge, skills, and attitudes (KSAs) and on several behavioral indexes., Results: Significant improvements were observed in self-reported and objectively measured KSAs across all cohorts. Additionally, GPP teams proved capable of producing quality drafts of basic community disaster plans in 1 day, and PFA trainees confirmed upon follow-up that their training proved useful in real-world trauma contexts. We documented examples of policy and practice changes at the levels of local and state health departments., Conclusions: Given appropriate guidance, LHDs and FBOs can implement an effective and potentially scalable model for promoting disaster mental health preparedness and community resilience, with implications for positive translational impact.

High intramuscular fat (IMF) awards price premiums to beef producers and is associated with meat quality and flavor. Studying gene interactions and pathways that affect IMF might unveil causative physiological mechanisms and inform genomic selection, leading to increased accuracy of predictions of breeding value. To study gene interactions and pathways, a gene network was derived from genetic markers associated with direct measures of IMF, other fat phenotypes, feedlot performance, and a number of meat quality traits relating to body conformation, development, and metabolism that might be plausibly expected to interact with IMF biology. Marker associations were inferred from genomewide association studies (GWAS) based on high density genotypes and 29 traits measured on 10,181 beef cattle animals from 3 breed types. For the network inference, SNP pairs were assessed according to the strength of the correlation between their additive association effects across the 29 traits. The co-association inferred network was formed by 2,434 genes connected by 28,283 edges. Topological network parameters suggested a highly cohesive network, in which the genes are strongly functionally interconnected. Pathway and network analyses pointed towards a trio of transcription factors (TF) as key regulators of carcass IMF: PPARGC1A, HNF4G, and FOXP3. Importantly, none of these genes would have been deemed as significantly associated with IMF from the GWAS. Instead, a total of 313 network genes show significant co-association with the 3 TF. These genes belong to a wide variety of biological functions, canonical pathways, and genetic networks linked to IMF-related phenotypes. In summary, our GWAS and network predictions are supported by the current literature and suggest a cooperative role for the 3 TF and other interacting genes including CAPN6, STC2, MAP2K4, EYA1, COPS5, XKR4, NR2E1, TOX, ATF1, ASPH, TGS1, and TTPA as modulators of carcass and meat quality traits in beef cattle.

Interest in genetic improvement of carcass and tenderness traits of beef cattle using genome-based selection (GS) and marker-assisted management programs is increasing. The success of such a program depends on the presence of linkage disequilibrium between the observed markers and the underlying QTL as well as on the relationship between the discovery, validation, and target populations. For molecular breeding values (MBV) predicted for a target population using SNP markers, reliabilities of these MBV can be obtained from validation analyses conducted in an independent population distinct from the discovery set. The objective of this study was to test MBV predicted for carcass and tenderness traits of beef cattle in a Canadian-based validation population that is largely independent of a United States-based discovery set. The discovery data set comprised of genotypes and phenotypes from >2,900 multibreed beef cattle while the validation population consisted of 802 crossbred feeder heifers and steers. A bivariate animal model that fitted actual phenotype and MBV was used for validation analyses. The reliability of MBV was defined as square of the genetic correlation (R(2) g) that represents the proportion of the additive genetic variance explained by the SNP markers. Several scenarios involving different starting marker panels (384, 3K, 7K, and 50K) and different sets of SNP selected to compute MBV (50, 100, 200, 375, 400, 600, and 800) were investigated. Validation results showed that the most reliable MBV (R(2) g) were 0.34 for HCW, 0.36 for back fat thickness, 0.28 for rib eye area, 0.30 for marbling score, 0.25 for yield grade, and 0.38 for Warner-Bratzler shear force across the different scenarios explored. The results indicate that smaller SNP panels can be developed for use in genetic improvement of beef carcass and tenderness traits to exploit GS benefits.

Pork quality and carcass characteristics are now being integrated into swine breeding objectives because of their economic value. Understanding the genetic basis for these traits is necessary for this to be accomplished. The objective of this study was to estimate phenotypic and genetic parameters for carcass and meat quality traits in 2 Canadian swine populations. Data from a genomic selection study aimed at improving meat quality with a mating system involving hybrid Landrace × Large White and Duroc pigs were used to estimate heritabilities and phenotypic and genetic correlations among them. Data on 2,100 commercial crossbred pigs for meat quality and carcass traits were recorded with pedigrees compromising 9,439 animals over 15 generations. Significant fixed effects (company, sex, and slaughter batch), covariates (cold carcass weight and slaughter age), and random additive and common litter effects were fitted in the models. A series of pairwise bivariate analyses were implemented in ASReml to estimate phenotypic and genetic parameters. Heritability estimates (±SE) for carcass traits were moderate to high and ranged from 0.22 ± 0.08 for longissimus dorsi muscle area to 0.63 ± 0.04 for trimmed ham weight, except for firmness, which was low. Heritability estimates (±SE) for meat quality traits varied from 0.10 ± 0.04 to 0.39 ± 0.06 for the Minolta b* of ham quadriceps femoris muscle and shear force, respectively. Generally, most of the genetic correlations were significant (P < 0.05) and ranged from low (0.18 ± 0.07) to high (-0.97 ± 0.35). There were high negative genetic correlations between drip loss with pH and shear force and a positive correlation with cooking loss. Genetic correlations between carcass weight (both hot and cold) with carcass marbling were highly positive. It was concluded that selection for increasing primal and subprimal cut weights with better pork quality may be possible. Furthermore, the use of pH is confirmed as an indicator for pork water-holding capacity and cooking loss. The heritabilities of carcass and pork quality traits indicated that they can be improved using traditional breeding methods and genomic selection, respectively. The estimated genetic parameters for carcass and meat quality traits can be incorporated into the breeding programs that emphasize product quality in these Canadian swine populations.

The primary purpose of spermatozoa is to deliver the paternal DNA to the oocyte at fertilization. During the complex events of fertilization, if the spermatozoon penetrating the oocyte contains compromised or damaged sperm chromatin, the subsequent progression of embryogenesis and foetal development may be affected. Variation in sperm DNA damage and protamine content in ejaculated spermatozoa was reported in the cattle, with potential consequences to bull fertility. Protamines are sperm-specific nuclear proteins that are essential to packaging of the condensed paternal genome in spermatozoa. Sperm DNA damage is thought to be repaired during the process of protamination. This study investigates the potential correlation between sperm protamine content, sperm DNA damage and the subsequent relationships between sperm chromatin and commonly measured reproductive phenotypes. Bos indicus sperm samples (n = 133) were assessed by two flow cytometric methods: the sperm chromatin structure assay (SCSA) and an optimized sperm protamine deficiency assay (SPDA). To verify the SPDA assay for bovine sperm protamine content, samples collected from testis, caput and cauda epididymidis were analyzed. As expected, mature spermatozoa in the cauda epididymidis had higher protamine content when compared with sperm samples from testis and caput epididymidis (p < 0.01). The DNA fragmentation index (DFI), determined by SCSA, was positively correlated (r = 0.33 ± 0.08, p < 0.05) with the percentage of spermatozoa that showed low protamine content using SPDA. Also, DFI was negatively correlated (r = -0.21 ± 0.09, p < 0.05) with the percentage of spermatozoa with high protamine content. Larger scrotal circumference contributes to higher sperm protamine content and lower content of sperm DNA damage (p < 0.05). In conclusion, sperm protamine content and sperm DNA damage are closely associated. Protamine deficiency is likely to be one of the contributing factors to DNA instability and damage, which can affect bull fertility., (© 2014 American Society of Andrology and European Academy of Andrology.)

Background: Previous genome-wide association studies have identified significant regions of the X chromosome associated with reproductive traits in two Bos indicus-influenced breeds: Brahman cattle and Tropical Composites. Two QTL regions on this chromosome were identified in both breeds as strongly associated with scrotal circumference measurements, a reproductive trait previously shown to be useful for selection of young bulls. Scrotal circumference is genetically correlated with early age at puberty in both male and female offspring. These QTL were located at positions 69-77 and 81-92 Mb respectively, large areas each to which a significant number of potential candidate genes were mapped., Results: To further characterise these regions, a bioinformatic approach was undertaken to identify novel non-synonymous SNP within the QTL regions of interest in Brahman cattle. After SNP discovery, we used conventional molecular assay technologies to perform studies of two candidate genes in both breeds. Non-synonymous SNP mapped to Testis-expressed gene 11 (Tex11) were associated (P < 0.001) with scrotal circumference in both breeds, and associations with percentage of normal sperm cells were also observed (P < 0.05). Evidence for recent selection was found as Tex11 SNP form a haplotype segment of Bos taurus origin that is retained within Brahman and Tropical Composite cattle with greatest reproductive potential., Conclusions: Association of non-synonymous SNP presented here are a first step to functional genetic studies. Bovine species may serve as a model for studying the role of Tex11 in male fertility, warranting further in-depth molecular characterisation.

Quality of pork from pigs raised either traditionally (outdoor access or bedded settings with no sub-therapeutic antibiotics or growth promotants in feed) or conventionally (commercial indoor) was evaluated. Pork loins (m. longissimus thoracis et lumborum, LTL) from four hundred pigs from either traditional or conventional production systems (n=200) fed commercially formulated diets ad libitum were harvested at slaughter. Intramuscular crude fat content and lean color (L* and b*) values were significantly decreased in conventional pork loins. LTL from conventionally-raised pig carcasses showed increased (P<0.05) mean pH, moisture content and reduced cooking loss and shear force values and had increased tenderness and juiciness scores compared to those from traditionally-raised pig carcasses. Results indicated that pork from conventionally raised pigs was superior to that from traditionally raised pigs in terms of tenderness and juiciness, suggesting that consumers may value pork from traditionally raised pigs on the basis of factors other than eating quality and appearance., (© 2013.)

This article documents the public availability of (i) raw transcriptome sequence data, assembled contigs and UniProt BLAST hits from common crossbill (Loxia curvirostra) and Plasmodium relictum (lineage SGS1) obtained from a controlled infection experiment; and (ii) raw transcriptome sequence data and 66 596 SNPs for the white-tailed deer (Odocoileus virginianus)., (© 2013 John Wiley & Sons Ltd.)

Objectives: Faculty and affiliates of the Johns Hopkins Preparedness and Emergency Response Research Center partnered with local health departments and faith-based organizations to develop a dual-intervention model of capacity-building for public mental health preparedness and community resilience. Project objectives included (1) determining the feasibility of the tri-partite collaborative concept; (2) designing, delivering, and evaluating psychological first aid (PFA) training and guided preparedness planning (GPP); and (3) documenting preliminary evidence of the sustainability and impact of the model., Methods: We evaluated intervention effectiveness by analyzing pre- and post-training changes in participant responses on knowledge-acquisition tests administered to three urban and four rural community cohorts. Changes in percent of correct items and mean total correct items were evaluated. Criteria for model sustainability and impact were, respectively, observations of nonacademic partners engaging in efforts to advance post-project preparedness alliances, and project-attributable changes in preparedness-related practices of local or state governments., Results: The majority (11 of 14) test items addressing technical or practical PFA content showed significant improvement; we observed comparable testing results for GPP training. Government and faith partners developed ideas and tools for sustaining preparedness activities, and numerous project-driven changes in local and state government policies were documented., Conclusions: Results suggest that the model could be an effective approach to promoting public health preparedness and community resilience.

A current challenge in genetic improvement of cattle is to identify genomic selection strategies that could work across breeds. Breed differences, scarcity of data, and lack of quantitative trait loci (QTL) validation contribute to this challenge. We conducted a review of the literature to identify QTL, markers, and candidate genes that are associated with fertility across breeds to arrive at an integrated view of bovine fertility genomics and to guide the direction of future studies. This review considers both male and female fertility traits as these are economically relevant for all breeds and production systems. Regions associated with fertility traits were found in each of the 30 bovine chromosomes, confirming the complexity of these polygenic traits. Across breeds, regions on chromosomes 1, 5, 14, and 16 were associated with female reproductive traits. The X chromosome was associated with male reproductive traits in both dairy and beef bulls. It has recently been proposed that a Y chromosome anomaly may be involved in infertility in cows. Knowledge of these QTL may assist discovery of causative mutations and has the potential to improve the accuracy of genomic selection, especially across breeds of cattle., (Copyright © 2013 Elsevier B.V. All rights reserved.)

The candidate gene approach was used to identify genes associated with residual feed intake (RFI) in beef steers. The approach uses prior knowledge of gene functions to predict their biological role in the variation observed in a trait. It is suited to identify genes associated with complex traits where each gene has a relatively small effect. First, positional candidate genes were identified within the genomic positions of previously reported QTL associated with component traits related to RFI such as dry matter intake (DMI), growth, feed conversion ratio (FCR), average daily gain (ADG), and energy balance. Secondly, the positional candidate genes were prioritized into functional candidate genes according to their biological functions and their relationship with the biological processes associated with RFI including carbohydrate, fat and protein metabolism, thermoregulation, immunity and muscle activity. Single nucleotide polymorphisms (SNPs) located within the functional candidate genes were identified using mRNA sequences and prioritized into functional classes such as non-synonymous (nsSNP), synonymous (sSNP) or intronic SNP. A total of 117 nsSNP were considered as functional SNP and genotyped in steers at the University of Alberta ranch in Kinsella. Multiple marker association analysis in ASReml was performed using RFI data obtained from 531 beef steers. Twenty-five SNP were significantly associated with RFI (P < 0.05) accounting for 19.7% of the phenotypic variation. Using SIFT program to predict the effect of the SNP on the function of the corresponding protein, 3 of the 25 SNP were predicted to cause a significant effect on protein function (P < 0.05). One of the 3 SNP was located in the GHR gene and was also associated with a significant effect on the tertiary structure of the GHR protein (P < 0.05) as modeled using SWISSModel software. Least square means for each genotype were estimated and an over-dominance effect was observed for the SNP located in the GHR, CAST, ACAD11 and UGT3A1 genes. In addition, 2 other SNP showed a dominance effect and 3 genes had an additive effect. Gene network analysis performed in Ingenuity pathway analysis (IPA) software (Ingenuity Systems, www.ingenuity.com) indicated that the significant genes were involved in biological pathways such as lipid, protein and energy metabolism, electron transport and membrane signaling. The genes in this study, if validated in other beef cattle populations, may be useful for marker assisted selection for feed efficiency.

Background: Hanwoo (Korean cattle), which originated from natural crossbreeding between taurine and zebu cattle, migrated to the Korean peninsula through North China. Hanwoo were raised as draft animals until the 1970s without the introduction of foreign germplasm. Since 1979, Hanwoo has been bred as beef cattle. Genetic variation was analyzed by whole-genome deep resequencing of a Hanwoo bull. The Hanwoo genome was compared to that of two other breeds, Black Angus and Holstein, and genes within regions of homozygosity were investigated to elucidate the genetic and genomic characteristics of Hanwoo., Results: The Hanwoo bull genome was sequenced to 45.6-fold coverage using the ABI SOLiD system. In total, 4.7 million single-nucleotide polymorphisms and 0.4 million small indels were identified by comparison with the Btau4.0 reference assembly. Of the total number of SNPs and indels, 58% and 87%, respectively, were novel. The overall genotype concordance between the SNPs and BovineSNP50 BeadChip data was 96.4%. Of 1.6 million genetic differences in Hanwoo, approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Among 1,045 genes containing reliable specific NS/SS/Is in Hanwoo, 109 genes contained more than one novel damaging NS/SS/I. Of the genes containing NS/SS/Is, 610 genes were assigned as trait-associated genes. Moreover, 16, 78, and 51 regions of homozygosity (ROHs) were detected in Hanwoo, Black Angus, and Holstein, respectively. 'Regulation of actin filament length' was revealed as a significant gene ontology term and 25 trait-associated genes for meat quality and disease resistance were found in 753 genes that resided in the ROHs of Hanwoo. In Hanwoo, 43 genes were located in common ROHs between whole-genome resequencing and SNP chips in BTA2, 10, and 13 coincided with quantitative trait loci for meat fat traits. In addition, the common ROHs in BTA2 and 16 were in agreement between Hanwoo and Black Angus., Conclusions: We identified 4.7 million SNPs and 0.4 million small indels by whole-genome resequencing of a Hanwoo bull. Approximately 25,000 non-synonymous SNPs, splice-site variants, and coding indels (NS/SS/Is) were detected in 8,360 genes. Additionally, we found 25 trait-associated genes for meat quality and disease resistance among 753 genes that resided in the ROHs of Hanwoo. These findings will provide useful genomic information for identifying genes or casual mutations associated with economically important traits in cattle.

Hanwoo, Korean native cattle, is indigenous to the Korean peninsula. They have been used mainly as draft animals for about 5,000 years; however, in the last 30 years, their main role has been changed to meat production by selective breeding which has led to substantial increases in their productivity. Massively parallel sequencing technology has recently made possible the systematic identification of structural variations in cattle genomes. In particular, copy number variation (CNV) has been recognized as an important genetic variation complementary to single-nucleotide polymorphisms that can be used to account for variations of economically important traits in cattle. Here we report genome-wide copy number variation regions (CNVRs) in Hanwoo cattle obtained by comparing the whole genome sequence of Hanwoo with Black Angus and Holstein sequence datasets. We identified 1,173 and 963 putative CNVRs representing 16.7 and 7.8 Mbp from comparisons between Black Angus and Hanwoo and between Holstein and Hanwoo, respectively. The potential functional roles of the CNVRs were assessed by Gene Ontology enrichment analysis. The results showed that response to stimulus, immune system process, and cellular component organization were highly enriched in the genic-CNVRs that overlapped with annotated cattle genes. Of the 11 CNVRs that were selected for validation by quantitative real-time PCR, 9 exhibited the expected copy number differences. The results reported in this study show that genome-wide CNVs were detected successfully using massively parallel sequencing technology. The CNVs may be a valuable resource for further studies to correlate CNVs and economically important traits in cattle.

This study aimed to evaluate whether the host genetic background impact the ruminal microbial communities of the progeny of sires from three different breeds under different diets. Eighty five bacterial and twenty eight methanogen phylotypes from 49 individuals of diverging sire breed (Angus, ANG; Charolais, CHA; and Hybrid, HYB), fed high energy density (HE) and low energy density (LE) diets were determined and correlated with breed, rumen fermentation and phenotypic variables, using multivariate statistical approaches. When bacterial phylotypes were compared between diets, ANG offspring showed the lowest number of diet-associated phylotypes, whereas CHA and HYB progenies had seventeen and twenty-three diet-associated phylotypes, respectively. For the methanogen phylotypes, there were no sire breed-associated phylotypes; however, seven phylotypes were significantly different among breeds on either diet (P<0.05). Sire breed did not influence the metabolic variables measured when high energy diet was fed. A correlation matrix of all pairwise comparisons among frequencies of bacterial and methanogen phylotypes uncovered their relationships with sire breed. A cluster containing methanogen phylotypes M16 (Methanobrevibacter gottschalkii) and M20 (Methanobrevibacter smithii), and bacterial phylotype B62 (Robinsoniella sp.) in Angus offspring fed low energy diet reflected the metabolic interactions among microbial consortia. The clustering of the phylotype frequencies from the three breeds indicated that phylotypes detected in CHA and HYB progenies are more similar among them, compared to ANG animals. Our results revealed that the frequency of particular microbial phylotypes in the progeny of cattle may be influenced by the sire breed when different diets are fed and ultimately further impact host metabolic functions, such as feed efficiency.

Background: Concerns have arisen over recent years about the absence of empirically derived evidence on which to base policy and practice in the public health system, in general, and to meet the challenge of public health emergency preparedness, in particular. Related issues include the challenge of disaster-caused, behavioral health surge, and the frequent exclusion of populations from studies that the research is meant to aid., Objective: To characterize the contributions of nonacademic collaborators to a series of projects validating a set of interventions to enhance capacity and competency of public mental health preparedness planning and response., Setting(s): Urban, suburban, and rural communities of the state of Maryland and rural communities of the state of Iowa., Participants: Study partners and participants (both of this project and the studies examined) were representatives of academic health centers (AHCs), local health departments (LHDs), and faith-based organizations (FBOs) and their communities., Procedures: A multiple-project, case study analysis was conducted, that is, four research projects implemented by the authors from 2005 through 2011 to determine the types and impact of contributions made by nonacademic collaborators to those projects. The analysis involved reviewing research records, conceptualizing contributions (and providing examples) for government, faith, and (nonacademic) institutional collaborators., Results: Ten areas were identified where partners made valuable contributions to the study series; these "value-areas" were as follows: 1) leadership and management of the projects; 2) formulation and refinement of research topics, aims, etc; 3) recruitment and retention of participants; 4) design and enhancement of interventions; 5) delivery of interventions; 6) collection, analysis, and interpretation of data; 7) dissemination of findings; 8) ensuring sustainability of faith/government preparedness planning relationships; 9) optimizing scalability and portability of the model; and 10) facilitating translational impact of study findings., Conclusions: Systems-based partnerships among academic, faith, and government entities offer an especially promising infrastructure for conducting participatory public health systems research in domestic emergency preparedness and response.

There is concern in the beef industry that selecting bulls for feed efficiency based on residual feed intake (RFI) may have a negative impact on bull reproductive performance and fertility. Here we investigated the impact of selection of bulls for low RFI on breeding soundness evaluation (BSE), reproductive performance, and fertility of bulls under natural service in multisire mating groups on pasture. Of the 412 RFI-tested bulls available, 98 (23.8%) were culled for performance, type, temperament, or other reasons, and 88 (21.4%) were culled for failing BSE, for an overall cull rate of 45.1%. From among the 314 bulls subjected to BSE, 32 (10.2%), 20 (6.4%), and 36 (11.4%) were culled for poor feet and legs, scrotal circumference, and semen quality, respectively. The BSE traits were not different (P > 0.10) between bulls categorized as either inefficient (+RFI) or efficient (-RFI), but the proportion of bulls that failed to meet the 60% minimum sperm motility requirement tended (P = 0.07) to be greater in the -RFI group than in the +RFI group (10.2% vs. 4.4%, respectively). In a subpopulation of 115 bulls, individual progressive sperm motility was greater (P < 0.05) in +RFI (85%) than -RFI (80%) bulls. A multisire natural mating experiment was conducted during 2 consecutive breeding seasons (2006 to 2007 and 2007 to 2008) using 18 +RFI and 18 -RFI bulls. The overall calving rate (calves born/cows exposed) was 72.9%. Mean number of progeny per sire was significantly greater (P < 0.01) in -RFI bulls (18.3) than in +RFI bulls (11.8). Selection for feed efficiency based on RFI appears to have no detrimental impact on reproductive performance and fertility in beef bulls bred in multisire groups on pasture. However, the decreased sperm motility and the greater number of progeny per sire associated with -RFI status need further investigation.

Prion diseases or transmissible spongiform encephalopathies (TSEs) are infectious neurodegenerative disorders leading to death. These include Cresutzfeldt-Jakob disease (CJD), familial, sporadic and variant CJD and kuru in humans; and animal TSEs include scrapie in sheep, bovine spongiform encephalopathy (BSE) in cattle, chronic wasting disease (CWD) of mule deer and elk, and transmissible mink encephalopathy. All these TSEs share common pathological features such as accumulation of mis-folded prion proteins in the central nervous system leading to cellular dysfunction and cell death. It is important to characterize the molecular pathways and events leading to prion induced neurodegeneration. Here we discuss the impact of the functional genomics approaches including microarrays, subtractive hybridization and microRNA profiling in elucidating transcriptional cascades at different stages of disease. Many of these transcriptional changes have been observed in multiple neurodegenerative diseases which may aid in identification of biomarkers for disease. A comprehensive characterization of expression profiles implicated in neurodegenerative disorders will undoubtedly advance our understanding on neuropathology and dysfunction during prion disease and other neurodegenerative disorders. We also present an outlook on the future work which may focus on analysis of structural genetic variation, genome and transcriptome sequencing using next generation sequencing with an integrated approach on animal and human TSE related studies.

Background: Linkage disequilibrium (LD) between genes at linked or independent loci can occur at gametic and zygotic levels known asgametic LD and zygotic LD, respectively. Gametic LD is well known for its roles in fine-scale mapping of quantitative trait loci, genomic selection and evolutionary inference. The less-well studied is the zygotic LD and its components that can be also estimated directly from the unphased SNPs., Results: This study was set up to investigate the genome-wide extent and patterns of zygotic LD and its components in a crossbred cattle population using the genomic data from the Illumina BovineSNP50 beadchip. The animal population arose from repeated crossbreeding of multiple breeds and selection for growth and cow reproduction. The study showed that similar genomic structures in gametic and zygotic LD were observed, with zygotic LD decaying faster than gametic LD over marker distance. The trigenic and quadrigenic disequilibria were generally two- to three-fold smaller than the usual digenic disequilibria (gametic or composite LD). There was less power of testing for these high-order genic disequilibria than for the digenic disequilibria. The power estimates decreased with the marker distance between markers though the decay trend is more obvious for the digenic disequilibria than for high-order disequilibria., Conclusions: This study is the first major genome-wide survey of all non-allelic associations between pairs of SNPs in a cattle population. Such analysis allows us to assess the relative importance of gametic LD vs. all other non-allelic genic LDs regardless of whether or not the population is in HWE. The observed predominance of digenic LD (gametic or composite LD) coupled with insignificant high-order trigenic and quadrigenic disequilibria supports the current intensive focus on the use of high-density SNP markers for genome-wide association studies and genomic selection activities in the cattle population.

Chronic wasting disease (CWD) is an invariably fatal neurologic disease that naturally infects mule deer, white tailed deer and elk. The understanding of CWD neurodegeneration at a molecular level is very limited. In this study, microarray analysis was performed to determine changes in the gene expression profiles in six different tissues including brain, midbrain, thalamus, spleen, RPLN and tonsil of CWD-infected elk in comparison to non-infected healthy elk, using 24,000 bovine specific oligo probes. In total, 329 genes were found to be differentially expressed (> 2.0-fold) between CWD negative and positive brain tissues, with 132 genes upregulated and 197 genes downregulated. There were 249 DE genes in the spleen (168 up- and 81 downregulated), 30 DE genes in the retropharyngeal lymph node (RPLN) (18 up- and 12 downregulated), and 55 DE genes in the tonsil (21 up- and 34 downregulated). Using Gene Ontology (GO), the DE genes were assigned to functional groups associated with cellular process, biological regulation, metabolic process, and regulation of biological process. For all brain tissues, the highest ranking networks for DE genes identified by Ingenuity Pathway Analysis (IPA) were associated with neurological disease, cell morphology, cellular assembly and organization. Quantitative real-time PCR (qRT-PCR) validated the expression of DE genes primarily involved in different regulatory pathways, including neuronal signaling and synapse function, calcium signaling, apoptosis and cell death and immune cell trafficking and inflammatory response. This is the first study to evaluate altered gene expression in multiple organs including brain from orally infected elk and the results will improve our understanding of CWD neurodegeneration at the molecular level.

Cattle are divided into 2 groups referred to as taurine and indicine, both of which have been under strong artificial selection due to their importance for human nutrition. A side effect of this domestication includes a loss of genetic diversity within each specialized breed. Recently, the first taurine genome was sequenced and assembled, allowing for a better understanding of this ruminant species. However, genetic information from indicine breeds has been limited. Here, we present the first genome sequence of an indicine breed (Nellore) generated with 52X coverage by SOLiD sequencing platform. As expected, both genomes share high similarity at the nucleotide level for all autosomes and the X chromosome. Regarding the Y chromosome, the homology was considerably lower, most likely due to uncompleted assembly of the taurine Y chromosome. We were also able to cover 97% of the annotated taurine protein-coding genes.

Fine mapping of quantitative trait loci (QTL) for 16 ultrasound measurements and carcass merit traits that were collected from 418 hybrid steers was conducted using 1207 SNP markers covering the entire genome. These SNP markers were evaluated using a Bayesian shrinkage estimation method and the empirical critical significant thresholds (α = 0.05 and α = 0.01) were determined by permutation based on 3500 permuted datasets for each trait to control the genome-wide type I error rates. The analyses identified a total of 105 QTLs (p < 0.05) for seven ultrasound measure traits including ultrasound backfat, ultrasound marbling and ultrasound ribeye area and 113 QTLs for seven carcass merit traits of carcass weight, grade fat, average backfat, ribeye area, lean meat yield, marbling and yield grade. Proportion of phenotypic variance accounted for by a single QTL ranged from 0.06% for mean ultrasound backfat to 4.83% for carcass marbling (CMAR) score, while proportion of the phenotypic variance accounted for by all significant (p < 0.05) QTL identified for a single trait ranged from 4.54% for carcass weight to 23.87% for CMAR., (© 2011 Blackwell Verlag GmbH.)

Limited knowledge of the structure and activities of the ruminal bacterial community prevents the understanding of the effect of population dynamics on functional bacterial groups and on host productivity. This study aimed to identify particular bacteria associated with host feed efficiency in steers with differing diets and residual feed intake (RFI) using culture-independent methods: PCR-denaturing gradient gel electrophoresis (DGGE) and quantitative real-time PCR analysis. PCR-DGGE profiles were generated from the ruminal fluid of 55 steers fed a low-energy-density diet and then switched to a high-energy-density diet. Bacterial profile comparisons by multivariate statistical analysis showed a trend only for RFI-related clusters on the high-energy diet. When steers (n = 19) belonging to the same RFI group under both diets were used to identify specific bacterial phylotypes related to feed efficiency traits, correlations were detected between dry matter intake, average daily gain, and copy numbers of the 16S rRNA gene of Succinivibrio sp. in low-RFI (efficient) steers, whereas correlations between Robinsoniella sp. and RFI (P < 0.05) were observed for high-RFI (inefficient) animals. Eubacterium sp. differed significantly (P < 0.05) between RFI groups that were only on the high-energy diet. Our work provides a comprehensive framework to understand how particular bacterial phylotypes contribute to differences in feed efficiency and ultimately influence host productivity, which may either depend on or be independent from diet factors.

As sequencing technology improves, an increasing number of projects aim to generate full genome sequence, even for nonmodel taxa. These projects may be feasibly conducted at lower read depths if the alignment can be aided by previously developed genomic resources from a closely related species. We investigated the feasibility of constructing a complete mitochondrial (mt) genome without preamplification or other targeting of the sequence. Here we present a full mt genome sequence (16,463 nucleotides) for the bighorn sheep (Ovis canadensis) generated though alignment of SOLiD short-read sequences to a reference genome. Average read depth was 1240, and each base was covered by at least 36 reads. We then conducted a phylogenomic analysis with 27 other bovid mitogenomes, which placed bighorn sheep firmly in the Ovis clade. These results show that it is possible to generate a complete mitogenome by skimming a low-coverage genomic sequencing library. This technique will become increasingly applicable as the number of taxa with some level of genome sequence rises.

The molecular mechanisms that regulate fat deposition in bovine adipose tissue have not been well studied. To elucidate the genes and gene networks involved in bovine fat development, transcriptional profiles of backfat (BF) tissues from Hereford × Aberdeen Angus (HEAN, n = 6) and Charolais × Red Angus (CHRA, n = 6) steers with high or low BF thickness were characterized by digital gene expression-tag profiling. Approximately 9.8 to 21.9 million tags were obtained for each library, and a total of 18,034 genes were identified. In total, 650 genes were found to be differentially expressed, with a greater than 1.5-fold difference between the 2 crossbreds (Benjamini-Hochberg false discovery rate ≤ 0.05). The majority of differentially expressed genes that were more highly expressed in CHRA vs. HEAN were associated with development, whereas the differentially expressed genes with greater expression in HEAN vs. CHRA were overrepresented in biological processes such as metabolism and immune response. Thirty-six and 152 differentially expressed genes were detected between animals with high (n = 3) and low (n = 3) BF thickness in HEAN and CHRA, respectively (Benjamini-Hochberg false discovery rate ≤0.05). The differentially expressed genes between high and low groups in CHRA were related to cell proliferation and development processes. In addition, lipid metabolism was 1 of the top 5 molecular and cellular functions identified in both crossbreds. Ten and 17 differentially expressed genes were found to be involved in fat metabolism in HEAN and CHRA, respectively. Genes associated with obesity, such as PTX3 (pentraxin 3, long) and SERPINE1 (serpin peptidase inhibitor, clade E, member 1), were more highly expressed (P < 0.05) in the subset of CHRA animals with greater BF thickness. Our study revealed that the expression patterns of genes in BF tissues differed depending on the genetic background of the cattle.

Estimating animal abundance in industrial scale batches of ground meat is important for mapping meat products through the manufacturing process and for effectively tracing the finished product during a food safety recall. The processing of ground beef involves a potentially large number of animals from diverse sources in a single product batch, which produces a high heterogeneity in capture probability. In order to estimate animal abundance through DNA profiling of ground beef constituents, two parameter-based statistical models were developed for incidence data. Simulations were applied to evaluate the maximum likelihood estimate (MLE) of a joint likelihood function from multiple surveys, showing superiority in the presence of high capture heterogeneity with small sample sizes, or comparable estimation in the presence of low capture heterogeneity with a large sample size when compared to other existing models. Our model employs the full information on the pattern of the capture-recapture frequencies from multiple samples. We applied the proposed models to estimate animal abundance in six manufacturing beef batches, genotyped using 30 single nucleotide polymorphism (SNP) markers, from a large scale beef grinding facility. Results show that between 411∼1367 animals were present in six manufacturing beef batches. These estimates are informative as a reference for improving recall processes and tracing finished meat products back to source.

Background: One of the goals of livestock genomics research is to identify the genetic differences responsible for variation in phenotypic traits, particularly those of economic importance. Characterizing the genetic variation in livestock species is an important step towards linking genes or genomic regions with phenotypes. The completion of the bovine genome sequence and recent advances in DNA sequencing technology allow for in-depth characterization of the genetic variations present in cattle. Here we describe the whole-genome resequencing of two Bos taurus bulls from distinct breeds for the purpose of identifying and annotating novel forms of genetic variation in cattle., Results: The genomes of a Black Angus bull and a Holstein bull were sequenced to 22-fold and 19-fold coverage, respectively, using the ABI SOLiD system. Comparisons of the sequences with the Btau4.0 reference assembly yielded 7 million single nucleotide polymorphisms (SNPs), 24% of which were identified in both animals. Of the total SNPs found in Holstein, Black Angus, and in both animals, 81%, 81%, and 75% respectively are novel. In-depth annotations of the data identified more than 16 thousand distinct non-synonymous SNPs (85% novel) between the two datasets. Alignments between the SNP-altered proteins and orthologues from numerous species indicate that many of the SNPs alter well-conserved amino acids. Several SNPs predicted to create or remove stop codons were also found. A comparison between the sequencing SNPs and genotyping results from the BovineHD high-density genotyping chip indicates a detection rate of 91% for homozygous SNPs and 81% for heterozygous SNPs. The false positive rate is estimated to be about 2% for both the Black Angus and Holstein SNP sets, based on follow-up genotyping of 422 and 427 SNPs, respectively. Comparisons of read depth between the two bulls along the reference assembly identified 790 putative copy-number variations (CNVs). Ten randomly selected CNVs, five genic and five non-genic, were successfully validated using quantitative real-time PCR. The CNVs are enriched for immune system genes and include genes that may contribute to lactation capacity. The majority of the CNVs (69%) were detected as regions with higher abundance in the Holstein bull., Conclusions: Substantial genetic differences exist between the Black Angus and Holstein animals sequenced in this work and the Hereford reference sequence, and some of this variation is predicted to affect evolutionarily conserved amino acids or gene copy number. The deeply annotated SNPs and CNVs identified in this resequencing study can serve as useful genetic tools, and as candidates in searches for phenotype-altering DNA differences.

Because of the moderate heritability and the expense associated with collecting feed intake data, effective selection for residual feed intake would be enhanced if marker-assisted evaluation were used for accurate estimation of genetic merit. In this study, a suite of genetic markers predictive of residual feed intake, DMI, and ADG were preselected using single-marker regression analysis, and the top 100 SNP were analyzed further to provide prediction equations for the traits. The data used consisted of 728 spring-born beef steers, offspring of a cross between a composite dam line and Angus, Charolais, or University of Alberta hybrid bulls. Feed intake data were collected over a 5-yr period, with 2 groups (fall-winter and winter-spring) tested every year. Training and validation data sets were obtained by splitting the data into 2 distinct sets, by randomly splitting the data into training and testing sets based on sire family (split 1) in 5 replicates or by retaining all animals with no known pedigree relationships as the validation set (split 2). A total of 37,959 SNP were analyzed by single-marker regression, of which only the top 100 that corresponded to a P-value <0.002 were retained. The 100 SNP were then analyzed using random regression BLUP, and only SNP that were jointly significant (P < 0.05) were included in the final marker panels. The marker effects from the selected panels were used to derive the molecular breeding values, which were calculated as a weighted sum of the number of copies of the more frequent allele at each SNP locus, with the weights being the allele substitution effects. The correlation between molecular breeding value and phenotype represented the accuracy of prediction. For all traits evaluated, accuracy across breeds was low, ranging between 0.007 and 0.414. Accuracy was least in data split 2, where the validation individuals had no pedigree relationship with animals in the training data. Given the low predictive ability observed, a large number of individuals may be needed for prediction when using such an admixed population. Further, these results suggest that breed composition of the target population in which the marker panels are likely to be used should be an important consideration when developing prediction equations across breeds, especially where an admixed population is used as the training data set.

Data from a 3-yr feeding trial of crossbred steers (n = 331) were used to examine the relationship between feeding behavior traits and feed efficiency in steers fed grower and finisher diets, successively. There were 2 feeding periods each year whereby the steers were fed a grower diet in the first feeding period (P1) and a finisher diet in the second feeding period (P2). Each feeding period lasted for a minimum of 10 wk, ad libitum. In addition to feed intake, records on 3 measures of feeding behavior [feeding duration (FD), head-down time (HDT), and feeding frequency (FF)] were collected using the GrowSafe feeding system. Residual feed intake (RFI) was calculated by regression, after which the steers were classified as low (<0.5 SD), medium (±0.5 SD), or high (>0.5 SD) from the mean. The steers had greater (P < 0.001) FD, HDT, and FF when the grower diet was fed but greater feeding rate (FR) when the finisher diet was fed. Including the measures of feeding behavior as covariates to the feed intake prediction model containing ADG, metabolic midweight, and ultrasound backfat accounted for more variation in DMI than models that did not contain these additional parameters. The FD and HDT were significantly different (P < 0.05) among the RFI classes regardless of the feeding period, whereas no differences (P > 0.90) were found for FR among the RFI classes. For the growing period and finishing period, respectively, FD had phenotypic correlations with HDT (0.79, 0.83), FF (0.14, 0.55), DMI (0.38, 0.34), and FR (-0.34, -0.21). Heritability estimates in P1 and P2 for FD, HDT, and FF were 0.25 ± 0.16, 0.14 ± 0.11; 0.14 ± 0.15, 0.09 ± 0.10; and 0.56 ± 0.19, 0.59 ± 0.18, respectively. Genetic correlations between P1 and P2 were 0.91 ± 0.26, 0.93 ± 0.37, and 0.94 ± 0.11 for FD, HDT, and FF, respectively. The results suggest that it may be appropriate to include feeding behavior traits as covariates to indicate measure(s) of animal activity in the calculation of RFI. Feeding behavior phenotypes were greater during the grower-fed period than the finisher-fed period. During these feeding periods, efficient steers exhibited fewer FF, shorter FD, and shorter HDT than inefficient steers.

The objective of this study was to examine the genetic parameters and genetic correlations of feed efficiency traits in steers (n = 490) fed grower or finisher diets in 2 feeding periods. A bivariate model was used to estimate phenotypic and genetic parameters using steers that received the grower and finisher diets in successive feeding periods, whereas a repeated animal model was used to estimate the permanent environmental effects. Genetic correlations between the grower-fed and finisher-fed regimens were 0.50 ± 0.48 and 0.78 ± 0.43 for residual feed intake (RFI) and G:F, respectively. The moderate genetic correlation between the 2 feeding regimens may indicate the presence of a genotype × environment interaction for RFI. Permanent environmental effects (expressed in percentage of phenotypic variance) were detected in the grower-fed steers for ADG (38%), DMI (30%), RFI (18%), and G:F (40%) and also in the finisher-fed steers for ADG (28%), DMI (35%), metabolic mid-weight (23%), and RFI (10%). Heritability estimates were 0.08 ± 0.10 and 0.14 ± 0.15 for the grower-fed steers and 0.42 ± 0.16 and 0.40 ± 17 for the finisher-fed steers for RFI and G:F, respectively. The dependency of the RFI on the feeding regimen may have serious implications when selecting animals in the beef industry. Because of the higher cost of grains, feed efficiency in the feedlot might be overemphasized, whereas efficiency in the cow herd and the backgrounding segments may have less emphasis. These results may also favor the retention (for subsequent breeding) of cows whose steers were efficient in the feedlot sector. Therefore, comprehensive feeding trials may be necessary to provide more insight into the mechanisms surrounding genotype × environment interaction in steers.

The benefit of using genomic breeding values (GEBV) in predicting ADG, DMI, and residual feed intake for an admixed population was investigated. Phenotypic data consisting of individual daily feed intake measurements for 721 beef cattle steers tested over 5 yr was available for analysis. The animals used were an admixed population of spring-born steers, progeny of a cross between 3 sire breeds and a composite dam line. Training and validation data sets were defined by randomly splitting the data into training and testing data sets based on sire family so that there was no overlap of sires in the 2 sets. The random split was replicated to obtain 5 separate data sets. Two methods (BayesB and random regression BLUP) were used to estimate marker effects and to define marker panels and ultimately the GEBV. The accuracy of prediction (the correlation between the phenotypes and GEBV) was compared between SNP panels. Accuracy for all traits was low, ranging from 0.223 to 0.479 for marker panels with 200 SNP, and 0.114 to 0.246 for marker panels with 37,959 SNP, depending on the genomic selection method used. This was less than accuracies observed for polygenic EBV accuracies, which ranged from 0.504 to 0.602. The results obtained from this study demonstrate that the utility of genetic markers for genomic prediction of residual feed intake in beef cattle may be suboptimal. Differences in accuracy were observed between sire breeds when the random regression BLUP method was used, which may imply that the correlations obtained by this method were confounded by the ability of the selected SNP to trace breed differences. This may also suggest that prediction equations derived from such an admixed population may be useful only in populations of similar composition. Given the sample size used in this study, there is a need for increased feed intake testing if substantially greater accuracies are to be achieved.

Bovine spongiform encephalopathy (BSE) is a fatal disorder in cattle characterized by progressive neurodegeneration of the central nervous system. We investigated the molecular mechanisms involved in neurodegeneration during prion infection through the identification of genes that are differentially expressed (DE) between experimentally infected and non-challenged cattle. Gene expression of caudal medulla from control and orally infected animals was compared by microarray analysis using 24,000 bovine oligonucleotides representing 16,846 different genes to identify DE genes associated with BSE disease. In total, 182 DE genes were identified between normal and BSE-infected tissues (>2.0-fold change, P < 0.01); 81 DE genes had gene ontology functions, which included synapse function, calcium ion regulation, immune and inflammatory response, apoptosis, and cytoskeleton organization; 13 of these genes were found to be involved in 26 different Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. The expression of five DE genes associated with synapse function (tachykinin, synuclein, neuropeptide Y, cocaine, amphetamine-responsive transcript, and synaptosomal-associated protein 25 kDa) and three DE genes associated with calcium ion regulation (parvalbumin, visinin-like, and cadherin) was further validated in the medulla tissue of cattle at different infection times (6, 12, 42, and 45 months post-infection) by qRT-PCR. These data will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species.

Adipogenesis, the complex development from preadipocytes or mesenchymal stem cells to mature adipocytes, is essential for fat formation and metabolism of adipose tissues in mammals. It has been reported to be regulated by hormones and various adipogenic transcription factors which are expressed as a transcriptional cascade promoting adipocyte differentiation, leading to the mature adipocyte phenotype. Recent findings indicate that microRNAs (miRNAs), a family of small RNA molecules of approximately 22 nucleotides in length, are involved in the regulatory network of many biological processes, including cell differentiation, through post-transcriptional regulation of transcription factors and/or other genes. In this review, we focus on the recent understanding of the roles of miRNAs in adipogenesis, including the most recent and relevant findings that support the role of several miRNAs as pro- or antiadipogenic factors regulating adipogenesis in mice, human and cattle to propose the future role of miRNA in adipogenesis of farm animal models.

The objective of this study was to identify single-nucleotide polymorphisms using a bovine chromosome 14 high-density SNP panel after accounting for the effect of DGAT1. Linkage disequilibrium information and sire heterozygosity were used to select markers for linkage analysis on bovine chromosome 14 for milk production traits in 321 Holstein animals. Results show putative milk peaks at 42 and 61 cM, both at p<0.10, a fat yield peak at 42 and 63 cM, both at p<0.05; a protein yield peak at 42 (p<0.01) and 84 cM (p<0.05); fat per cent peaks at 3 (p<0.01) and 29 cM (p<0.05), and a protein per cent peak at 4 cM (p<0.05). Once quantitative trait loci positions were established, allele substitution effects for all markers were evaluated using the same statistical model. Overlaying information between quantitative trait loci (QTL) and allele effect analysis enabled the identification (p<0.01) of 20 SNPs under the milk yield QTL, 2 under both of the fat yield peaks, 8 and 9 under the protein yield peaks, 2 and 6 for the fat per cent peaks and 5 for the protein per cent peak. One SNP in particular, ss61514555:A>C, showed association with 3 of the 5 traits: milk (p=1.59E-04), fat (p=6.88E-05) and protein yields (p=5.76E-05). Overall, combining information from linkage disequilibrium, sire heterozygosity and genetic knowledge of traits enabled the characterization of additional markers with significant associations with milk production traits., (© 2011 Blackwell Verlag GmbH.)

This 3-yr study used 490 steers to determine whether feedlot steers changed their feed efficiency (FE) ranking when fed a grower diet, then a finisher diet. The steers were crossbreds and were between 5 to 7 mo of age. There were 2 feeding periods each year. Within each year, approximately 90 steers had their diet switched from a grower to a finisher diet (feed-swap group), whereas another 90 steers were fed either the grower (grower-fed group) or the finisher (finisher-fed group) diet throughout the feeding trial. Each feeding test lasted for a minimum of 10 wk, and all steers were fed ad libitum. Individual animal feed intakes were collected using the GrowSafe feeding system, and BW were measured every 2 wk. Residual feed intake (RFI), G:F, and Kleiber ratio (KR) were computed at the end of each feeding period. For each measure of efficiency, animals were classified as low, medium, or high based on 0.5 SD from the mean. The majority of steers did not maintain the previous efficiency class in the second period. Approximately 58, 51, and 51% of steers in the feed-swap group, finisher-fed group, and the grower-fed group, respectively, changed their RFI measure by 0.5 SD. A low rank correlation occurred in all test groups but was less in the feed-swap group. Spearman rank correlations between the 2 feeding periods in the feed-swap group were 0.33, 0.20, and 0.31 for RFI, G:F, and KR, respectively. Classifications based on G:F and KR showed that a greater number of steers (P < 0.05) in the feed-swap group did not maintain their FE class from 1 feeding regimen to the other, whereas classification based on RFI did not show any difference (P > 0.05) between the proportions of individuals that changed or maintained their FE class. In the groups without a feed-swap, there was no difference (P > 0.05) in the proportion of steers that changed or maintained the same FE class for all FE measures. Our results suggest that diet type and feeding period affect the FE ranking in beef steers. A feedlot diet is ideal for evaluating the FE potential of steers for feedlot profitability; however, we suggest that tests involving less dense diets should be examined in an effort to understand the relationships between FE and feeder profitability.

Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Sequence variations in the coding region of the prion gene (PRNP) have been associated with acquired transmissible spongiform encephalopathy (TSE) susceptibility in mammals; however, this is not the case in cattle. It has been hypothesized that genes, in addition to the prion gene, contribute to genetic susceptibility of acquired TSEs. Accordingly, genetic studies of classical BSE in cattle identified loci other than PRNP that are associated with disease incidence. The objective of this study was to utilize a genome-wide association study to test for genetic loci associated with classical BSE. The samples include 143 BSE affected (case) and 173 unaffected half sib (control) animals collected in the mid 1990s in Southern England. The data analysis identifies loci on two different chromosomes associated with BSE disease occurrence. Most notable is a single nucleotide polymorphism on chromosome 1 at 29.15 Mb that is associated with BSE disease (p = 3.09E-05). Additionally, a locus on chromosome 14, within a cluster of SNPs showed a trend toward significance (p = 5.24E-05). It is worth noting that in a human vCJD study markers on human chromosome 8, a region with shared synteny to the region identified on cattle chromosome 14, were associated with disease. Further, our candidate genes appear to have plausible biological relevance with the known etiology of TSE disease. One of the candidate genes is hypothetical gene LOC521010, similar to FK506 binding protein 2 located on chromosome 1 at 29.32 Mb. This gene encodes a protein that is a member of the immunophilin protein family and is involved in basic cellular processes including protein folding. The chromosomal regions identified in this study and candidate genes within these regions merit further investigation.

The identification of variations in gene expression in response to bovine spongiform encephalopathy (BSE) may help to elucidate the mechanisms of neuropathology and prion replication and discover biomarkers for disease. In this study, genes that are differentially expressed in the caudal medulla tissues of animals infected with different doses of PrP(BSE) at 12 and 45 mo post infection were compared using array containing 24,000 oligonucleotide probes. Data analysis identified 966 differentially expressed (DE) genes between control and infected animals. Genes identified in at least two of four experiments (control versus 1-g infected animals at 12 and 45-mo; control versus 100-g infected animals at 12 and 45 mo) were considered to be the genes that may be associated with BSE disease. From the 176 DE genes associated with BSE, 84 had functions described in the Gene Ontology (GO) database. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 14 genes revealed that prion infection may cause dysfunction of several different networks, including extracellular matrix (ECM), cell adhesion, neuroactive ligand-receptor interaction, complement and coagulation cascades, MAPK signaling, neurodegenerative disorder, SNARE interactions in vesicular transport, and the transforming growth factor (TGF) beta signaling pathways. The identification of DE genes will contribute to a better understanding of the molecular mechanisms of neuropathology in bovine species. Additional studies on larger number of animals are in progress in our laboratory to investigate the roles of these DE genes in pathogenesis of BSE.

Bovine spongiform encephalopathy (BSE) is a transmissible, fatal neurodegenerative disorder of cattle produced by prions. The use of excessive parallel sequencing for comparison of gene expression in bovine control and infected tissues may help to elucidate the molecular mechanisms associated with this disease. In this study, tag profiling Solexa sequencing was used for transcriptome analysis of bovine brain tissues. Replicate libraries were prepared from mRNA isolated from control and infected (challenged with 100 g of BSE-infected brain) medulla tissues 45 mo after infection. For each library, 5-6 million sequence reads were generated and approximately 67-70% of the reads were mapped against the Bovine Genome database to approximately 13,700-14,120 transcripts (each having at least one read). About 42-47% of the total reads mapped uniquely. Using the GeneSifter software package, 190 differentially expressed (DE) genes were identified (>2.0-fold change, p < .01): 73 upregulated and 117 downregulated. Seventy-nine DE genes had functions described in the Gene Ontology (GO) database and 16 DE genes were involved in 38 different pathways described in the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Digital analysis expression by tag profiling may be a powerful approach to comprehensive transcriptome analysis to identify changes associated with disease progression, leading to a better understanding of the underlying mechanism of pathogenesis of BSE.

This study sought to assess whether residual feed intake (RFI) calculated by regressing feed intake (DMI) on growth rate (ADG) and metabolic mid-BW in 3 different ways led to similar estimates of genetic parameters and variance components for young growing cattle tested for feed intake in fall and winter seasons. A total of 378 beef steers in 5 cohorts were fed a typical high energy feedlot diet and had free-choice access to feed and water. Feed intake data were collected in fall or winter seasons. Climate data were obtained from the University of Alberta Kinsella meteorological station and Vikings AGCM station. Individual animal RFI was obtained by either fitting a regression model to each test group separately (RFI(C)), fitting a regression model to pooled data consisting of all cohorts but including test group as a fixed effect (RFI(O)), or fitting a regression to pooled data with test group as a fixed effect but within seasonal (fall-winter or winter-spring) groups (RFI(S)). Two animal models (M1 and M2) that differed by the inclusion of fixed effects of test group or season, respectively, were used to evaluate RFI measurements. Feed intake was correlated with air temperature, relative humidity, solar radiation, and wind speed (-0.26, 0.23, 0.30, -0.14 for fall-winter and 0.31, -0.04, 0.14, 0.16 for winter-spring, respectively), but the nature and magnitude of the correlations were different for the 2 seasons. Single trait direct heritability, model likelihood, direct genetic variance, and EBV accuracy estimates were greatest for RFI(C) and least for RFI(O) for both M1 and M2 models. A significant genetic correlation was also observed between RFI(O) and ADG, but not for RFI(C) and RFI(S). Including a season effect (M2) in the genetic evaluation of RFI(O) resulted in the smallest heritability, model LogL, EBV accuracy, and largest residual variance estimates. These results, though not conclusive, suggest a possible effect of seasonality on feed intake and thus feed efficiency.

The influence of rumen microbial structure and functions on host physiology remains poorly understood. This study aimed to investigate the interaction between the ruminal microflora and the host by correlating bacterial diversity with fermentation measurements and feed efficiency traits, including dry matter intake, feed conversion ratio, average daily gain, and residual feed intake, using culture-independent methods. Universal bacterial partial 16S rRNA gene products were amplified from ruminal fluid collected from 58 steers raised under a low-energy diet and were subjected to PCR-denaturing gradient gel electrophoresis (DGGE) analysis. Multivariate statistical analysis was used to relate specific PCR-DGGE bands to various feed efficiency traits and metabolites. Analysis of volatile fatty acid profiles showed that butyrate was positively correlated with daily dry matter intake (P < 0.05) and tended to have higher concentration in inefficient animals (P = 0.10), while isovalerate was associated with residual feed intake (P < 0.05). Our results suggest that particular bacteria and their metabolism in the rumen may contribute to differences in host feed efficiency under a low-energy diet. This is the first study correlating PCR-DGGE bands representing specific bacteria to metabolites in the bovine rumen and to host feed efficiency traits.

Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease of cattle. The bovine prion gene (PRNP) contains regions of both high and low linkage disequilibrium (LD) that appear to be conserved across Bos taurus populations. The region of high LD, which spans the promoter and part of intron 2, contains polymorphic loci that have been associated with classical BSE status. However, the complex genetic architecture of PRNP has not been systematically tested for an association with classical BSE., Methodology/principal Findings: In this study, haplotype tagging single nucleotide polymorphisms (htSNPs) within PRNP were used to test for association between PRNP haplotypes and BSE disease. A combination of Illumina goldengate assay, sequencing and PCR amplification was used to genotype 18 htSNPs and 2 indels in 95 BSE case and 134 control animals. A haplotype within the region of high LD was found to be associated with BSE unaffected animals (p-value=0.000114)., Conclusion/significance: A PRNP haplotype association with classical BSE incidence has been identified. This result suggests that a genetic determinant in or near PRNP may influence classical BSE incidence in cattle.

Background: MicroRNAs (miRNAs), a family of small non-coding RNA molecules, appear to regulate animal lipid metabolism and preadipocyte conversion to form lipid-assimilating adipocytes (i.e. adipogenesis). However, no miRNA to date has been reported to modulate adipogenesis and lipid deposition in beef cattle., Results: The expression patterns of 89 miRNAs including four bovine specific miRNAs in subcutaneous adipose tissues from three groups of crossbred steers differing in backfat thickness were compared using qRT-PCR analysis. Eighty-six miRNAs were detectable in all samples, with 42 miRNAs differing among crossbreds (P < 0.05) and 15 miRNAs differentially expressed between tissues with high and low backfat thickness (P < 0.05). The expression levels of 18 miRNAs were correlated with backfat thickness (P < 0.05). The miRNA most differentially expressed and the most strongly associated with backfat thickness was miR-378, with a 1.99-fold increase in high backfat thickness tissues (r = 0.72)., Conclusions: MiRNA expression patterns differed significantly in response to host genetic components. Approximately 20% of the miRNAs in this study were identified as being correlated with backfat thickness. This result suggests that miRNAs may play a regulatory role in white adipose tissue development in beef animals.

Background: Classical bovine spongiform encephalopathy (BSE) is an acquired prion disease that is invariably fatal in cattle and has been implicated as a significant human health risk. Polymorphisms that alter the prion protein of sheep or humans have been associated with variations in transmissible spongiform encephalopathy susceptibility or resistance. In contrast, there is no strong evidence that non-synonymous mutations in the bovine prion gene (PRNP) are associated with classical BSE disease susceptibility. However, two bovine PRNP insertion/deletion polymorphisms, one within the promoter region and the other in intron 1, have been associated with susceptibility to classical BSE. These associations do not explain the full extent of BSE susceptibility, and loci outside of PRNP appear to be associated with disease incidence in some cattle populations. To test for associations with BSE susceptibility, we conducted a genome wide scan using a panel of 3,072 single nucleotide polymorphism (SNP) markers on 814 animals representing cases and control Holstein cattle from the United Kingdom BSE epidemic., Results: Two sets of BSE affected Holstein cattle were analyzed in this study, one set with known family relationships and the second set of paired cases with controls. The family set comprises half-sibling progeny from six sires. The progeny from four of these sires had previously been scanned with microsatellite markers. The results obtained from the current analysis of the family set yielded both some supporting and new results compared with those obtained in the earlier study. The results revealed 27 SNPs representing 18 chromosomes associated with incidence of BSE disease. These results confirm a region previously reported on chromosome 20, and identify additional regions on chromosomes 2, 14, 16, 21 and 28. This study did not identify a significant association near the PRNP in the family sample set. The only association found in the PRNP region was in the case-control sample set and this was not significant after multiple test correction. The genome scan of the case-control animals did not identify any associations that passed a stringent genome-wide significance threshold., Conclusions: Several regions of the genome are statistically associated with the incidence of classical BSE in European Holstein cattle. Further investigation of loci on chromosomes 2, 14, 16, 20, 21 and 28 will be required to uncover any biological significance underlying these marker associations.