QTL-mapping and genomic prediction for bovine respiratory disease in U.S. Holsteins using sequence imputation and feature selection

Background: National genetic evaluations for disease resistance do not exist, precluding the genetic improvement of cattle for these traits. We imputed BovineHD genotypes to whole genome sequence for 2703 Holsteins that were cases or controls for Bovine Respiratory Disease and sampled from either California or New Mexico to construct and compare genomic prediction models. The sequence variation reference dataset comprised variants called for 1578 animals from Run 5 of the 1000 Bull Genomes Project, including 450 Holsteins and 29 animals sequenced from this study population. Genotypes for 9,282,726 variants with minor allele frequencies ?5 percent were imputed and used to obtain genomic predictions in GEMMA using a Bayesian Sparse Linear Mixed Model. Results: Variation explained by markers increased from 13.6 percent using BovineHD data to 14.4 percent using imputed whole genome sequence data and the resolution of genomic regions detected as harbouring QTL substantially increased. Explained variation in the analysis of the combined California and New Mexico data was less than when data for each state were separately analysed and the estimated genetic correlation between risk of Bovine Respiratory Disease in California and New Mexico Holsteins was - 0.36. Consequently, genomic predictions trained using the data from one state did not accurately predict disease risk in the other state. To determine if a prediction model could be developed with utility in both states, we selected variants within genomic regions harbouring: 1) genes involved in the normal immune response to infection by pathogens responsible for Bovine Respiratory Disease detected by RNA-Seq analysis, and/or 2) QTL identified in the association analysis of the imputed sequence variants. The model based on QTL selected variants is biased but when trained in one state generated BRD risk predictions with positive accuracies in the other state. Conclusions: We demonstrate the utility of sequence-based and biology-driven model development for genomic selection. Disease phenotypes cannot be routinely recorded in most livestock species and the observed phenotypes may vary in their genomic architecture due to variation in the pathogen composition across environments. Elucidation of trait biology and genetic architecture may guide the development of prediction models with utility across breeds and environments

Results of survey of stakeholders regarding knowledge of and attitudes towards feed intake, efficiency and genetic improvement concepts

Individual animal feed efficiency plays a key role in the profitability and sustainability of the US beef industry. During the growing and finishing phase of production, a 10% improvement in feed efficiency has a two-fold greater impact on profit than a 10% increase in rate of gain (Fox et al., 2001). The traits that beef producers routinely record are outputs which determine the value of product sold and not the inputs defining the cost of beef production. The inability to routinely measure feed intake and feed efficiency on large numbers of cattle has precluded the efficient application of selection despite moderate heritabilities (h2 = 0.16-0.46; Archer et al., 1999). Feed costs in calf feeding and yearling finishing systems account for approximately 66% and 77% of costs, respectively (Anderson et al., 2005).Feed costs account for approximately 65% of total beef production costs. Of the metabolizable energy required from conception to consumption of a beef animal, 72% is utilized during the cow-calf segment of production while 28% of calories are utilized in the calf growing and finishing phases of production (Ferrell and Jenkins, 1982). Of the calories consumed in the cow-calf segment, more than half are used for maintenance which presents a large selection target

Frequencies of polymorphisms associated with BSE resistance differ significantly between Bos taurus, Bos indicus, and composite cattle

<p>Abstract</p> <p>Background</p> <p>Transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases that affect several mammalian species. At least three factors related to the host prion protein are known to modulate susceptibility or resistance to a TSE: amino acid sequence, atypical number of octapeptide repeats, and expression level. These factors have been extensively studied in breeds of <it>Bos taurus </it>cattle in relation to classical bovine spongiform encephalopathy (BSE). However, little is currently known about these factors in <it>Bos indicus </it>purebred or <it>B. indicus </it>× <it>B. taurus </it>composite cattle. The goal of our study was to establish the frequency of markers associated with enhanced susceptibility or resistance to classical BSE in <it>B. indicus </it>purebred and composite cattle.</p> <p>Results</p> <p>No novel or TSE-associated <it>PRNP</it>-encoded amino acid polymorphisms were observed for <it>B. indicus </it>purebred and composite cattle, and all had the typical number of octapeptide repeats. However, differences were observed in the frequencies of the 23-bp and 12-bp insertion/deletion (indel) polymorphisms associated with two bovine <it>PRNP </it>transcription regulatory sites. Compared to <it>B. taurus</it>, <it>B. indicus </it>purebred and composite cattle had a significantly lower frequency of 23-bp insertion alleles and homozygous genotypes. Conversely, <it>B. indicus </it>purebred cattle had a significantly higher frequency of 12-bp insertion alleles and homozygous genotypes in relation to both <it>B. taurus </it>and composite cattle. The origin of these disparities can be attributed to a significantly different haplotype structure within each species.</p> <p>Conclusion</p> <p>The frequencies of the 23-bp and 12-bp indels were significantly different between <it>B. indicus </it>and <it>B. taurus </it>cattle. No other known or potential risk factors were detected for the <it>B. indicus </it>purebred and composite cattle. To date, no consensus exists regarding which bovine <it>PRNP </it>indel region is more influential with respect to classical BSE. Should one particular indel region and associated genotypes prove more influential with respect to the incidence of classical BSE, differences regarding overall susceptibility and resistance for <it>B. indicus </it>and <it>B. taurus </it>cattle may be elucidated.</p

Gene expression profiling of primary cultures of ovarian epithelial cells identifies novel molecular classifiers of ovarian cancer

In order to elucidate the biological variance between normal ovarian surface epithelial (NOSE) and epithelial ovarian cancer (EOC) cells, and to build a molecular classifier to discover new markers distinguishing these cells, we analysed gene expression patterns of 65 primary cultures of these tissues by oligonucleotide microarray. Unsupervised clustering highlights three subgroups of tumours: low malignant potential tumours, invasive solid tumours and tumour cells derived from ascites. We selected 18 genes with expression profiles that enable the distinction of NOSE from these three groups of EOC with 92% accuracy. Validation using an independent published data set derived from tissues or primary cultures confirmed a high accuracy (87–96%). The distinctive expression pattern of a subset of genes was validated by quantitative reverse transcription–PCR. An ovarian-specific tissue array representing tissues from NOSE and EOC samples of various subtypes and grades was used to further assess the protein expression patterns of two differentially expressed genes (Msln and BMP-2) by immunohistochemistry. This study highlights the relevance of using primary cultures of epithelial ovarian cells as a model system for gene profiling studies and demonstrates that the statistical analysis of gene expression profiling is a useful approach for selecting novel molecular tumour markers

Expression of the Bovine NK-Lysin Gene Family and Activity against Respiratory Pathogens

Unlike the genomes of many mammals that have a single NK-lysin gene, the cattle genome contains a family of four genes, one of which is expressed preferentially in the lung. In this study, we compared the expression of the four bovine NK-lysin genes in healthy animals to animals challenged with pathogens known to be associated with bovine respiratory disease (BRD) using transcriptome sequencing (RNA-seq). The expression of several NK-lysins, especially NK2C, was elevated in challenged relative to control animals. The effects of synthetic peptides corresponding to functional region helices 2 and 3 of each gene product were tested on both model membranes and bio-membranes. Circular dichroism spectroscopy indicated that these peptides adopted a more helical secondary structure upon binding to an anionic model membrane and liposome leakage assays suggested that these peptides disrupt membranes. Bacterial killing assays further confirmed the antimicrobial effects of these peptides on BRD-associated bacteria, including both Pasteurella multocida and Mannhemia haemolytica and an ultrastructural examination of NK-lysin-treated P. multocida cells by transmission electron microscopy revealed the lysis of target membranes. These studies demonstrate that the expanded bovine NK-lysin gene family is potentially important in host defense against pathogens involved in bovine respiratory disease

Identification by whole genome sequencing of genes associated with delayed postoperative hemorrhage in Scottish deerhounds

Abstract Background Delayed postoperative hemorrhage (DEPOH) is an important health concern for Scottish deerhounds. Hypothesis/Objectives Identify genes associated with DEPOH in Scottish deerhounds. Animals Two hundred sixty‐nine privately owned Scottish deerhounds. Methods Retrospective case‐control study. DEPOH cases and controls were identified through an owner health survey. Genome‐wide association analysis was performed using whole genome sequences from 8 cases and 17 controls. All cases and controls were genotyped for selected variants. Results Of 269 dogs, 10 met inclusion and exclusion criteria for DEPOH, while 62 controls had undergone similar surgical procedures without DEPOH. Genome‐wide association analysis identified a single locus on chromosome 9 spanning 40 genes. One of these genes (SERPINF2 encoding alpha‐2 antiplasmin) was directly linked to the pathophysiology of DEPOH. The entire cohort was genotyped for a missense SERPINF2 variant (c.605 C>T; p.A202V). Compared to dogs with the reference C/C genotype, the likelihood of DEPOH was significantly higher for dogs with the T/T genotype (odds ratio [OR] = 1235; 95% confidence interval [CI] = 23‐6752; P = 0.0005) and with the C/T genotype (OR = 28; 95% CI = 1.4‐542; P = 0.03). Conclusions and Clinical Importance SERPINF2 is associated with DEPOH in Scottish deerhounds. Genetic testing might be able to identify dogs that are susceptible to DEPOH