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

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

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

Meta-analysis of two genome-wide association studies of bovine paratuberculosis

Bovine paratuberculosis (ParaTB) also known as Johne's disease, is a contagious fatal disease resulting from infection by Mycobacterium avium subspecies paratuberculosis (MAP). Previous studies have identified loci associated with ParaTB using different measurements to define cases and controls. The objective of this study was to combine the data from two recent studies to identify genetic loci associated with MAP tissue infection and humoral immune response, defined by MAP ELISA-positive cattle, by comparing cases and control animals for one or both measures of infection. The two populations used for the association analyses were a cohort of MAP tissue infected animals and control Holstein cows from the USA and the second cohort composed of ELISA-positive and ELISA-negative Holstein cows from Italy. Altogether 1190 cattle were genotyped with the Illumina BovineSNP50 BeadChip. SNP markers were removed if the minor allele frequency 5%. Animals were removed with >5% genotyping failure. Whole genome association analyses were conducted with the GRAMMAR-CG method using two different definitions of control populations. The analyses identified several loci (P<5 e-05) associated with ParaTB, defined by positive ELISA and presence of bacteria in tissue compared to ELISA and tissue negative animals, on chromosomes 1, 12 and 15 and one unassigned SNP. These results confirmed associations on chromosome 12 and the unassigned SNP with ParaTB which had been found in the Italian population alone. Furthermore, several additional genomic regions were found associated with ParaTB when ELISA and tissue positive animals were compared with tissue negative samples. These loci were on chromosomes 1, 6, 7, 13, 16, 21,23 and 25 (P<5 e-05). The results clearly indicate the importance of the phenotype definition when seeking to identify markers associated with different disease responses

Loci associated with conception rate in crossbred beef heifers.

The inability of beef cattle to maintain full term pregnancies has become an economic concern for the beef industry. Herd management and nutritional improvements have alleviated environmental impacts on embryonic and fetal loss, yet additional gains can be made through genomic selection. The objectives of this study were to identify loci and gene-sets in crossbred beef heifers associated with the number of services required to become pregnant (TBRD) and heifer conception rate at first service (HCR1). Heifers (n = 709) from a commercial beef operation underwent one round of artificial insemination, before exposure to bulls for natural service for 50 days. Pregnancy and time of conception was determined by ultrasound 35 days after the breeding season. Heifers were genotyped using the GeneSeek (Lincoln, NE) Bovine GGP50K BeadChip prior to genome-wide association analyses (GWAA) conducted using an EIGENSTRAT-like model to identify loci associated (P < 1 × 10-5) with TBRD and HCR1. One locus was associated (P = 8.97 × 10-6) with TBRD on BTA19 and included the positional candidate gene ASIC2, which is differentially expressed in the endometrium of fertility classified heifers, and the positional candidate gene, SPACA3. Gene-set enrichment analyses using SNP (GSEA-SNP) data, was performed and identified one gene-set, oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen as enriched (NES = 3.15) with TBRD and contained nine leading edge genes that contributed to the enrichment of the gene set. The enriched gene-set is involved in catalyzing oxidation-reduction reactions, which have been associated with oxidative stressors impacting pregnancy success. No loci were associated nor gene-sets enriched with HCR1. Identification of loci, positional candidate genes, gene-sets and leading edge genes enriched for fertility facilitate genomic selection that allows producers to select for reproductively superior cattle, reduce costs associated with infertility, and increase percent calf crop

Tissue tropism in host transcriptional response to members of the bovine respiratory disease complex.

Bovine respiratory disease (BRD) is the most common infectious disease of beef and dairy cattle and is characterized by a complex infectious etiology that includes a variety of viral and bacterial pathogens. We examined the global changes in mRNA abundance in healthy lung and lung lesions and in the lymphoid tissues bronchial lymph node, retropharyngeal lymph node, nasopharyngeal lymph node and pharyngeal tonsil collected at the peak of clinical disease from beef cattle experimentally challenged with either bovine respiratory syncytial virus, infectious bovine rhinotracheitis, bovine viral diarrhea virus, Mannheimia haemolytica or Mycoplasma bovis. We identified signatures of tissue-specific transcriptional responses indicative of tropism in the coordination of host?s immune tissue responses to infection by viral or bacterial infections. Furthermore, our study shows that this tissue tropism in host transcriptional response to BRD pathogens results in the activation of different networks of response genes. The differential crosstalk among genes expressed in lymphoid tissues was predicted to be orchestrated by specific immune genes that act as ?key players? within expression networks. The results of this study serve as a basis for the development of innovative therapeutic strategies and for the selection of cattle with enhanced resistance to BRD.Made available in DSpace on 2019-02-21T00:47:34Z (GMT). No. of bitstreams: 1 11TissueTropisminHostTranscriptionalResponsetoMembersoftheBovineRespiratoryDiseaseComplex.pdf: 2935433 bytes, checksum: 7f2db937dad9b124831b34007d4ab7a1 (MD5) Previous issue date: 2019-02-20bitstream/item/193126/1/11-Tissue-Tropism-in-Host-Transcriptional-Response-to-Members-of-the-Bovine-Respiratory-Disease-Complex.pd