Publications by authors named "Sameer D Pant"

20 Publications

  • Page 1 of 1

Johne's Disease in Dairy Cattle: An Immunogenetic Perspective.

Front Vet Sci 2021 26;8:718987. Epub 2021 Aug 26.

Department of Animal Biosciences, Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, ON, Canada.

Johne's disease (JD), also known as paratuberculosis, is a severe production-limiting disease with significant economic and welfare implications for the global cattle industry. Caused by infection with subspecies (MAP), JD manifests as chronic enteritis in infected cattle. In addition to the economic losses and animal welfare issues associated with JD, MAP has attracted public health concerns with potential association with Crohn's disease, a human inflammatory bowel disease. The lack of effective treatment options, such as a vaccine, has hampered JD control resulting in its increasing global prevalence. The disease was first reported in 1895, but in recognition of its growing economic impact, extensive recent research facilitated by a revolution in technological approaches has led to significantly enhanced understanding of the immunological, genetic, and pathogen factors influencing disease pathogenesis. This knowledge has been derived from a variety of diverse models to elucidate host-pathogen interactions including and experimental infection models, studies measuring immune parameters in naturally-infected animals, and by studies conducted at the population level to enable the estimation of genetic parameters, and the identification of genetic markers and quantitative trait loci (QTL) putatively associated with susceptibility or resistance to JD. The main objectives of this review are to summarize these recent developments from an immunogenetics perspective and attempt to extract the principal and common findings emerging from this wealth of recent information. Based on these analyses, and in light of emerging technologies such as gene-editing, we conclude by discussing potential future avenues for effectively mitigating JD in cattle.
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http://dx.doi.org/10.3389/fvets.2021.718987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426623PMC
August 2021

Characterization of Breed Specific Differences in Spermatozoal Transcriptomes of Sheep in Australia.

Genes (Basel) 2021 01 30;12(2). Epub 2021 Jan 30.

Graham Centre for Agricultural Innovation (Charles Sturt University and NSW Department of Primary Industries), Charles Sturt University, Wagga Wagga, NSW 2678, Australia.

Reduced reproductive efficiency results in economic losses to the Australian sheep industry. Reproductive success, particularly after artificial insemination, is dependent on a number of contributing factors on both ewe and ram sides. Despite considerable emphasis placed on characterising ewe side contributions, little emphasis has been placed on characterising ram side contributions to conception success. Over 14,000 transcripts are in spermatozoa of other species, which are transferred to the ova on fertilisation. These transcripts conceivably influence early embryonic development and whether conception is successful. Semen was collected ( = 45) across three breeds; Merino, Dohne, and Poll Dorset. Following collection, each ejaculate was split in two; an aliquot was assessed utilising Computer Assisted Semen Analysis (CASA) and the remaining was utilised for RNA extraction and subsequent next-generation sequencing. Overall, 754 differentially expressed genes were identified in breed contrasts and contrast between ejaculates of different quality. Downstream analysis indicated that these genes could play significant roles in a broad range of physiological functions, including maintenance of spermatogenesis, fertilisation, conception, embryonic development, and offspring production performance. Overall results provide evidence that the spermatozoal transcriptome could be a crucial contributing factor in improving reproductive performance as well as in the overall productivity and profitability of sheep industries.
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http://dx.doi.org/10.3390/genes12020203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7912062PMC
January 2021

PGRMC1 effects on metabolism, genomic mutation and CpG methylation imply crucial roles in animal biology and disease.

BMC Mol Cell Biol 2020 Apr 15;21(1):26. Epub 2020 Apr 15.

School of Biomedical Sciences, Charles Sturt University, Wagga Wagga, NSW, 2650, Australia.

Background: Progesterone receptor membrane component 1 (PGRMC1) is often elevated in cancers, and exists in alternative states of phosphorylation. A motif centered on PGRMC1 Y180 was evolutionarily acquired concurrently with the embryological gastrulation organizer that orchestrates vertebrate tissue differentiation.

Results: Here, we show that mutagenic manipulation of PGRMC1 phosphorylation alters cell metabolism, genomic stability, and CpG methylation. Each of several mutants elicited distinct patterns of genomic CpG methylation. Mutation of S57A/Y180/S181A led to increased net hypermethylation, reminiscent of embryonic stem cells. Pathways enrichment analysis suggested modulation of processes related to animal cell differentiation status and tissue identity, as well as cell cycle control and ATM/ATR DNA damage repair regulation. We detected different genomic mutation rates in culture.

Conclusions: A companion manuscript shows that these cell states dramatically affect protein abundances, cell and mitochondrial morphology, and glycolytic metabolism. We propose that PGRMC1 phosphorylation status modulates cellular plasticity mechanisms relevant to early embryological tissue differentiation.
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http://dx.doi.org/10.1186/s12860-020-00268-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160964PMC
April 2020

The effect of false mount on quality of frozen-thawed semen in Bos indicus beef bulls.

J Vet Med Sci 2020 May 23;82(5):673-677. Epub 2020 Mar 23.

School of Animal & Veterinary Sciences, Charles Sturt University, Wagga Wagga, NSW-2678, Australia.

This study evaluated the effect of false mounts (FM) on quality of frozen-thawed semen in beef bulls. Five mature Brahman bulls at the Standard Semen Production Center in Thailand were subjected to semen collection. Overall, 60 ejaculates were collected over a 12-week period of which 30 were collected without, and another 30 were collected using FM. A range of quality parameters of fresh, pre-frozen, and frozen-thawed semen were evaluated. Use of FM resulted in significant improvement of most parameters of fresh semen except progressive motility and sperm viability. The quality parameters of pre-frozen and frozen-thawed semen also significantly improved with FM. Use of FM significantly improved the viability of frozen-thawed semen, possibly indicating the protective effect of seminal plasma proteins.
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http://dx.doi.org/10.1292/jvms.20-0025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7273598PMC
May 2020

Rapid detection of Bovicola ovis using colourimetric loop-mediated isothermal amplification (LAMP): a potential tool for the detection of sheep lice infestation on farm.

Parasitol Res 2020 Feb 10;119(2):395-401. Epub 2019 Dec 10.

School of Animal and Veterinary Sciences, Charles Sturt University, Wagga Wagga, New South Wales, 2678, Australia.

The sheep body louse, Bovicola ovis (B. ovis), is one of the most significant ectoparasites affecting Australia's sheep flocks. Despite this, detection methods for B. ovis infestation are limited to visual inspection and ELISA. A colourimetric loop-mediated isothermal amplification (LAMP) method was developed and evaluated for the detection of B. ovis DNA. Diagnostic sensitivity and specificity of LAMP were compared with those of visual inspection and PCR and validated using field samples collected from 22 farms. Two different DNA extraction methods using a commercial kit and a boiling method were also compared. The highest sensitivity and specificity were observed when PCR was used and DNA was extracted using a commercial kit. Compared with PCR, the LAMP assay demonstrated a sensitivity and specificity of 90% and 92% when DNA was extracted by a commercial kit and 100% and 75% when DNA was extracted by the boiling method, respectively. The LAMP test developed in this study could potentially serve as a point-of-care diagnostic tool for monitoring of sheep flocks as well as surveillance of B. ovis populations.
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http://dx.doi.org/10.1007/s00436-019-06552-yDOI Listing
February 2020

Haplotypes on pig chromosome 3 distinguish metabolically healthy from unhealthy obese individuals.

PLoS One 2017 1;12(6):e0178828. Epub 2017 Jun 1.

Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

We have established a pig resource population specifically designed to elucidate the genetics involved in development of obesity and obesity related co-morbidities by crossing the obesity prone Göttingen Minipig breed with two lean production pig breeds. In this study we have performed genome wide association (GWA) to identify loci with effect on blood lipid levels. The most significantly associated single nucleotide polymorphisms (SNPs) were used for linkage disequilibrium (LD) and haplotype analyses. Three separate haploblocks which influence the ratio between high density lipoprotein cholesterol and total cholesterol (HDL-C/CT), triglycerides (TG) and low density lipoprotein cholesterol (LDL-C) levels respectively were identified on Sus Scrofa chromosome 3 (SSC3). Large additive genetic effects were found for the HDL-C/CT and LDL-C haplotypes. Haplotypes segregating from Göttingen Minipigs were shown to impose a positive effect on blood lipid levels. Thus, the genetic profile of the Göttingen Minipig breed seems to support a phenotype comparable to the metabolic healthy obese (MHO) phenotype in humans.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0178828PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453593PMC
September 2017

Comparative Analyses of QTLs Influencing Obesity and Metabolic Phenotypes in Pigs and Humans.

PLoS One 2015 8;10(9):e0137356. Epub 2015 Sep 8.

Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The pig is a well-known animal model used to investigate genetic and mechanistic aspects of human disease biology. They are particularly useful in the context of obesity and metabolic diseases because other widely used models (e.g. mice) do not completely recapitulate key pathophysiological features associated with these diseases in humans. Therefore, we established a F2 pig resource population (n = 564) designed to elucidate the genetics underlying obesity and metabolic phenotypes. Segregation of obesity traits was ensured by using breeds highly divergent with respect to obesity traits in the parental generation. Several obesity and metabolic phenotypes were recorded (n = 35) from birth to slaughter (242 ± 48 days), including body composition determined at about two months of age (63 ± 10 days) via dual-energy x-ray absorptiometry (DXA) scanning. All pigs were genotyped using Illumina Porcine 60k SNP Beadchip and a combined linkage disequilibrium-linkage analysis was used to identify genome-wide significant associations for collected phenotypes. We identified 229 QTLs which associated with adiposity- and metabolic phenotypes at genome-wide significant levels. Subsequently comparative analyses were performed to identify the extent of overlap between previously identified QTLs in both humans and pigs. The combined analysis of a large number of obesity phenotypes has provided insight in the genetic architecture of the molecular mechanisms underlying these traits indicating that QTLs underlying similar phenotypes are clustered in the genome. Our analyses have further confirmed that genetic heterogeneity is an inherent characteristic of obesity traits most likely caused by segregation or fixation of different variants of the individual components belonging to cellular pathways in different populations. Several important genes previously associated to obesity in human studies, along with novel genes were identified. Altogether, this study provides novel insight that may further the current understanding of the molecular mechanisms underlying human obesity.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0137356PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4562524PMC
May 2016

Genome-wide association and pathway analysis of feed efficiency in pigs reveal candidate genes and pathways for residual feed intake.

Front Genet 2014 9;5:307. Epub 2014 Sep 9.

Section of Animal Genetics, Bioinformatics and Breeding, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen Frederiksberg, Denmark.

Residual feed intake (RFI) is a complex trait that is economically important for livestock production; however, the genetic and biological mechanisms regulating RFI are largely unknown in pigs. Therefore, the study aimed to identify single nucleotide polymorphisms (SNPs), candidate genes and biological pathways involved in regulating RFI using Genome-wide association (GWA) and pathway analyses. A total of 596 Yorkshire boars with phenotypes for two different measures of RFI (RFI1 and 2) and 60k genotypic data was used. GWA analysis was performed using a univariate mixed model and 12 and 7 SNPs were found to be significantly associated with RFI1 and RFI2, respectively. Several genes such as xin actin-binding repeat-containing protein 2 (XIRP2),tetratricopeptide repeat domain 29 (TTC29),suppressor of glucose, autophagy associated 1 (SOGA1),MAS1,G-protein-coupled receptor (GPCR) kinase 5 (GRK5),prospero-homeobox protein 1 (PROX1),GPCR 155 (GPR155), and FYVE domain containing the 26 (ZFYVE26) were identified as putative candidates for RFI based on their genomic location in the vicinity of these SNPs. Genes located within 50 kbp of SNPs significantly associated with RFI and RFI2 (q-value ≤ 0.2) were subsequently used for pathway analyses. These analyses were performed by assigning genes to biological pathways and then testing the association of individual pathways with RFI using a Fisher's exact test. Metabolic pathway was significantly associated with both RFIs. Other biological pathways regulating phagosome, tight junctions, olfactory transduction, and insulin secretion were significantly associated with both RFI traits when relaxed threshold for cut-off p-value was used (p ≤ 0.05). These results implied porcine RFI is regulated by multiple biological mechanisms, although the metabolic processes might be the most important. Olfactory transduction pathway controlling the perception of feed via smell, insulin pathway controlling food intake might be important pathways for RFI. Furthermore, our study revealed key genes and genetic variants that control feed efficiency that could potentially be useful for genetic selection of more feed efficient pigs.
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http://dx.doi.org/10.3389/fgene.2014.00307DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4159030PMC
September 2014

Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network, and pathway analyses.

Front Genet 2014 9;5:214. Epub 2014 Jul 9.

Animal Genetics, Bioinformatics and Breeding Section, Department of Veterinary Clinical and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen Copenhagen, Denmark.

Obesity is a complex condition with world-wide exponentially rising prevalence rates, linked with severe diseases like Type 2 Diabetes. Economic and welfare consequences have led to a raised interest in a better understanding of the biological and genetic background. To date, whole genome investigations focusing on single genetic variants have achieved limited success, and the importance of including genetic interactions is becoming evident. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip. Firstly, Genome Wide Association (GWA) analysis was performed on the Obesity Index to locate candidate genomic regions that were further validated using combined Linkage Disequilibrium Linkage Analysis and investigated by evaluation of haplotype blocks. We built Weighted Interaction SNP Hub (WISH) and differentially wired (DW) networks using genotypic correlations amongst obesity-associated SNPs resulting from GWA analysis. GWA results and SNP modules detected by WISH and DW analyses were further investigated by functional enrichment analyses. The functional annotation of SNPs revealed several genes associated with obesity, e.g., NPC2 and OR4D10. Moreover, gene enrichment analyses identified several significantly associated pathways, over and above the GWA study results, that may influence obesity and obesity related diseases, e.g., metabolic processes. WISH networks based on genotypic correlations allowed further identification of various gene ontology terms and pathways related to obesity and related traits, which were not identified by the GWA study. In conclusion, this is the first study to develop a (genetic) obesity index and employ systems genetics in a porcine model to provide important insights into the complex genetic architecture associated with obesity and many biological pathways that underlie it.
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http://dx.doi.org/10.3389/fgene.2014.00214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4087325PMC
July 2014

Molecular mechanisms regulating ocular apoptosis in zebrafish gdf6a mutants.

Invest Ophthalmol Vis Sci 2013 Aug 28;54(8):5871-9. Epub 2013 Aug 28.

Department of Ophthalmology, University of Alberta, Edmonton, Canada.

Purpose: To characterize the molecular mechanisms underlying retinal apoptosis induced by loss of Gdf6, a TGFβ ligand.

Methods: The role of Gdf6 in regulating apoptosis was studied using a zebrafish gdf6a(-/-) mutant, which encodes a truncated, nonfunctional protein. To investigate whether intrinsic or extrinsic apoptotic mechanisms were involved, morpholino antisense oligonucleotides targeting baxa, baxb, and p53 were employed. Caspase-3 immunohistochemistry (IHC) was performed to assay apoptosis. Pharmacologic inhibition (using SB203580) and IHC were used to investigate the role of p38 mitogen activated protein (MAP) kinase activation in gdf6a(-/-)-induced apoptosis. To assess the role of Gdf6a in transcriptional regulation of TGFβ signal transducers, in situ hybridization (ISH) was performed using probes to smad1, 5, 7, and 8.

Results: Results indicate maximal ocular apoptosis occurs 28 hours post fertilization (hpf) in gdf6a(-/-) mutants that is mediated independently of p53 by intrinsic mechanisms involving Bax proteins. Also, gdf6a(-/-) mutants exhibit markedly increased p38 MAP kinase activation that can be inhibited to significantly reduce retinal apoptosis. A reduction in retinal smad1 expression was also noted in gdf6a(-/-) mutants.

Conclusions: gdf6a(-/-)-induced apoptosis is characterized by the involvement of intrinsic apoptotic pathways, p38 MAP kinases, and dysregulated smad expression. Modulation of key mediators can inhibit retinal apoptosis offering potential avenues of therapy. However, the efficacy of pharmacomodulation in improvement of visual function needs to be further examined.
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http://dx.doi.org/10.1167/iovs.12-11315DOI Listing
August 2013

Proteomic analysis of plasma from Holstein cows testing positive for Mycobacterium avium subsp. paratuberculosis (MAP).

Vet Immunol Immunopathol 2012 Aug 7;148(3-4):243-51. Epub 2012 May 7.

Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada.

Johne's disease (JD) is a widespread and economically important chronic inflammatory disease of the small intestine of ruminants caused by Mycobacterium avium subsp. paratuberculosis (MAP). Although there are several techniques available for diagnosis of JD, their sensitivity is questionable. New proteome profiling methods, such as serum/plasma protein fingerprinting by 2-Dimensional Fluorescence Difference Gel Electrophoresis (2D-DIGE), may therefore be useful for identifying novel protein biomarkers of MAP infection. In this study, plasma samples were collected from 380 Holstein cows and screened for the presence of MAP infection using the M.pt. Johne's antibody Kit (IDEXX). Five negative (MAP-), and 5 strongly positive (MAP+) cows were selected for proteomic analysis. Highly abundant proteins were depleted from the plasma samples using the ProteoMiner technology (Bio-Rad) to enhance the resolution of low abundance proteins. Plasma samples from MAP-, MAP+, and a pooled internal control were labelled with different fluorescent dyes and separated based on their isoelectrical point (IP) and then their molecular weight. Gel images of the fluorescent plasma protein maps were acquired using a Typhoon scanner and analyzed using the DeCyder software. Proteins that were differentially expressed were excised from the gels, trypsin digested, and subjected to MS/MS analysis for identification. Six proteins were identified as being up-regulated at least 2-fold in MAP+ cows including: transferrin, gelsolin isoforms α & β (actin binding protein - ABP), complement subcomponent C1r, complement component C3, amine oxidase - copper containing 3 (AOC3), and coagulation factor II (thrombin) (p<0.05). Two proteins that were down-regulated approximately 2-fold in the MAP+ cows included coagulation factor XIII -B polypeptide (COAFXIII), and fibrinogen γ chain (FGG) and its precursor.
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http://dx.doi.org/10.1016/j.vetimm.2012.05.002DOI Listing
August 2012

Use of breed-specific single nucleotide polymorphisms to discriminate between Holstein and Jersey dairy cattle breeds.

Anim Biotechnol 2012 ;23(1):1-10

Department of Animal and Poultry Science, Centre for Genetic Improvement of Livestock, Guelph, Ontario, Canada.

Emphasis on livestock genetic improvement in the past decades has led to commercialization of different breeds of livestock species. Breed validation has become increasingly important to assess the safety and authenticity of livestock products in global and domestic markets. The objective of this study was to evaluate the use of breed-specific single nucleotide polymorphisms (SNPs) in discriminating between Holstein and Jersey dairy cattle breeds. Two separate resource populations were used, including a reference population consisting of 498 Holstein and 83 Jersey bull DNA samples, and a validation population consisting of 260 Holstein and 34 Jersey cow DNA samples. Five Jersey-specific and four Holstein-specific SNPs were identified and genotyped on the reference and validation resource populations. The reference population was used to validate the breed-specific SNPs used in this study and to predict the allocation efficiencies and misclassification probabilities of different combinations of SNPs. Individual animals in the validation population were allocated to either breed based on the presence of breed-specific alleles. It was found that any combination of three breed-specific SNPs had, on average, high breed allocation efficiency of >95% and low misclassification probability of <5%. In conclusion, this study demonstrates a simple, yet effective, method of using breed-specific SNPs to discriminate between Jersey and Holstein cattle breeds.
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http://dx.doi.org/10.1080/10495398.2012.636224DOI Listing
May 2012

Bovine IFNGR2, IL12RB1, IL12RB2, and IL23R polymorphisms and MAP infection status.

Mamm Genome 2011 Oct 20;22(9-10):583-8. Epub 2011 May 20.

Department of Animal and Poultry Science, Centre for Genetic Improvement of Livestock, University of Guelph, ON N1G 2W1, Canada.

Mycobacterium avium ssp. paratuberculosis (MAP) infection causes a chronic granulomatous inflammatory condition of the bovine gut that is characterized by diarrhea, progressive weight loss, and emaciation, and ultimately leads to loss in productivity and profitability of dairy operations. The host cytokine machinery is known to play an important role in protecting against MAP infection. Therefore, the goal of the present study was to assess whether polymorphisms in candidate genes encoding important cytokines and cytokine receptors are associated with MAP infection status of dairy cattle. MAP infection status was evaluated based on serum and milk enzyme-linked immunosorbent assays (ELISAs) for MAP-specific antibodies. Twenty previously reported polymorphisms in genes encoding bovine interferon gamma (IFNG), IFNGR1, IFNGR2, IL22, IL22RA1, IL12RB1, IL12RB2, and IL23R were genotyped in a resource population of 446 dairy Holsteins with known MAP infection status, and logistic regression was used to assess the statistical association with a binomial MAP infection status phenotype. Four SNPs in IFNGR2, IL12RB1, IL12RB2, and IL23R were found to be associated with the MAP infection status of the resource population. These results underscore the importance of cytokines and their receptors in conferring protection against MAP infection and warrant further functional characterization of these associations.
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http://dx.doi.org/10.1007/s00335-011-9332-8DOI Listing
October 2011

Identification of SNPs in interferon gamma, interleukin-22, and their receptors and associations with health and production-related traits in Canadian Holstein bulls.

Anim Biotechnol 2011 Jan;22(1):7-15

Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada.

Genetic variants in a number of immunoregulatory genes have been previously associated with health and production traits in dairy cattle. Therefore, in the following study, the genes coding interferon gamma (IFNG), IFNG receptor 1 and 2 domains, interleukin-22 (IL22), and IL22 receptor alpha 1, were investigated for single nucleotide polymorphisms (SNPs) in Holstein bulls. These SNPs, along with SNPs previously identified in IL10, IL10 receptor, and transforming growth factor beta 1 (TGFB1) genes, were evaluated for statistical associations to estimated breeding values for milk somatic cell score (SCS), a trait highly correlated to mastitis incidence, and various production-related traits, including milk yield, protein yield, fat yield, and lactation persistency. While no significant associations were found between these SNPs and SCS, SNPs in IL10 receptor beta subunit showed a significant effect on protein yield and lactation persistency. While there is evidence that IL10 plays an important role during lactation, it is also likely that the effects of SNPs in IL10 receptor beta subunit on protein yield and lactation persistency are due to linkage disequilibrium with a neighboring QTL.
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http://dx.doi.org/10.1080/10495398.2011.536078DOI Listing
January 2011

Gene expression profiling of PBMCs from Holstein and Jersey cows sub-clinically infected with Mycobacterium avium ssp. paratuberculosis.

Vet Immunol Immunopathol 2010 Sep 10;137(1-2):1-11. Epub 2010 Apr 10.

Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario N1G2W1, Canada.

Infection of calves with intracellular Mycobacterium avium ssp. paratuberculosis (MAP) commonly results in a granulomatous, chronic inflammatory bowel disease known as Johne's disease. The asymptomatic stage of this infection can persist for the entire production life of an adult cow, resulting in reduced performance and premature culling, as well as transmission of MAP to progeny and herd-mates. It has been previously shown that the gene expression profiles of peripheral blood mononuclear cells (PBMCs) of healthy cows, and those chronically infected with MAP are inherently different, and that these changes may be indicative of disease progression. Since resistance to MAP infection is a heritable trait, and has been proposed to differ amongst domestic dairy cattle breeds, the objective of the present study was to compare gene expression profiles of PBMCs from healthy adult Holstein and Jersey cows to those considered to be sub-clinically infected with MAP, as indicated by serum ELISA. Microarray analysis using a platform containing more than 10,000 probes and ontological analysis identified differences in gene expression between a) healthy and infected cows, including genes involved in the inflammatory response, and calcium binding, and b) infected Holsteins and Jerseys, including genes involved in the immune response, and antigen processing and presentation. These results suggest a mixed pro- and anti-inflammatory phenotype of PBMCs from MAP-infected as compared to healthy control animals, and inherently different levels of immune and inflammatory-related gene expression between MAP-infected Holsteins and Jerseys.
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http://dx.doi.org/10.1016/j.vetimm.2010.03.026DOI Listing
September 2010

Polymorphisms in the gene encoding bovine interleukin-10 receptor alpha are associated with Mycobacterium avium ssp. paratuberculosis infection status.

BMC Genet 2010 Apr 15;11:23. Epub 2010 Apr 15.

Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, 50 Stone Rd East, Guelph, Ontario, N1G2W1, Canada.

Background: Johne's disease is a chronic inflammatory bowel disease (IBD) of ruminants caused by Mycobacterium avium ssp. paratuberculosis (MAP). Since this pathogen has been implicated in the pathogenesis of human IBDs, the goal of this study was to assess whether single nucleotide polymorphism (SNPs) in several well-known candidate genes for human IBD are associated with susceptibility to MAP infection in dairy cattle.

Methods: The bovine candidate genes, interleukin-10 (IL10), IL10 receptor alpha/beta (IL10RA/B), transforming growth factor beta 1 (TGFB1), TGFB receptor class I/II (TGFBR1/2), and natural resistance-associated macrophage protein 1 (SLC11A1) were sequenced for SNP discovery using pooled DNA samples, and the identified SNPs were genotyped in a case-control association study comprised of 242 MAP negative and 204 MAP positive Holstein dairy cattle. Logistic regression was used to determine the association of SNPs and reconstructed haplotypes with MAP infection status.

Results: A total of 13 SNPs were identified. Four SNPs in IL10RA (984G > A, 1098C > T, 1269T > C, and 1302A > G) were tightly linked, and showed a strong additive and dominance relationship with MAP infection status. Haplotypes AGC and AAT, containing the SNPs IL10RA 633C > A, 984G > A and 1185C > T, were associated with an elevated and reduced likelihood of positive diagnosis by serum ELISA, respectively.

Conclusions: SNPs in IL10RA are associated with MAP infection status in dairy cattle. The functional significance of these SNPs warrants further investigation.
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http://dx.doi.org/10.1186/1471-2156-11-23DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873551PMC
April 2010

A principal component regression based genome wide analysis approach reveals the presence of a novel QTL on BTA7 for MAP resistance in holstein cattle.

Genomics 2010 Mar 7;95(3):176-82. Epub 2010 Jan 7.

Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1.

Bovine Johne's disease (JD), caused by Mycobacterium avium spp. paratuberculosis (MAP), causes significant losses to the dairy and beef cattle industries. Effective vaccination or therapeutic strategies against this disease are currently unavailable and infected animals either get culled or die due to clinical disease. An alternative strategy to manage the disease is to selectively breed animals with enhanced resistance to MAP infection. Therefore, the objective of this study was to identify genetic loci putatively associated with MAP infection in a resource population consisting of Holstein cattle using a genome-wide association approach. The BovineSNP50 BeadChip, containing 54,001 single nucleotide polymorphisms (SNPs), was used to genotype 232 animals with known MAP infection status. Since, traditional case-control analytical techniques are based on single-marker analysis and do not account for the existence of linkage disequilibrium (LD) between markers, we used a novel principal component regression approach, where each SNP was fit in a logistic regression model, along with principal components of other SNPs on the same chromosome showing association with the trait, as covariates. Such an approach allowed us to account for the LD that exists between multiple markers showing an association on the same chromosome. Our analysis revealed the presence of at least 12 genomic regions on BTA1, 5, 6, 7, 10, 11 and 14 that were associated with the MAP infection status of our resource population. A brief description of these genomic regions, and a discussion of the analysis used in this study, have been presented.
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http://dx.doi.org/10.1016/j.ygeno.2010.01.001DOI Listing
March 2010

SNPs in the bovine IL-10 receptor are associated with somatic cell score in Canadian dairy bulls.

Mamm Genome 2009 Jul 30;20(7):447-54. Epub 2009 Jul 30.

Department of Animal and Poultry Science, Centre for Genetic Improvement of Livestock, University of Guelph, Guelph, N1G 2W1, ON, Canada.

Altering the balance between pro- and anti-inflammatory responses can influence an animal's susceptibility to acute or chronic inflammatory disease; bovine mastitis is no exception. Genetic variation in the form of single nucleotide polymorphisms (SNPs) may alter the function and expression of genes that regulate inflammation, making them important candidates for defining an animal's risk of developing acute or chronic mastitis. The objective of the present study was to identify SNPs in genes that regulate anti-inflammatory responses and test their association with estimated breeding values (EBVs) for somatic cell score (SCS), a trait highly correlated with the incidence of mastitis. These genes included bovine interleukin-10 (IL-10) and its receptor (IL-10R), and transforming growth factor beta1 (TGF-beta1) and its receptor (TGF-betaR). Sequencing-pooled DNA allowed for the identification of SNPs in IL-10 (n = 2), IL-10Ralpha (n = 6) and beta (n = 2), and TGF-beta1 (n = 1). These SNPs were subsequently genotyped in a cohort of Holstein (n = 500), Jersey (n = 83), and Guernsey (n = 50) bulls. Linear regression analysis identified significant SNP effects for IL-10Ralpha 1185C>T with SCS. Haplotype IL-10Ralpha AAT showed a significant effect on increasing SCS compared to the most common haplotype. The results presented here indicate that SNPs in IL-10Ralpha may contribute to variation in the SCS of dairy cattle. Although functional studies are necessary to ascertain whether these SNPs are causal polymorphisms or merely in linkage with the true causal SNP(s), a selection program incorporating these markers could have a beneficial influence on the average SCS and productivity of a dairy herd.
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http://dx.doi.org/10.1007/s00335-009-9198-1DOI Listing
July 2009

The genome sequence of taurine cattle: a window to ruminant biology and evolution.

Science 2009 Apr;324(5926):522-8

To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.
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http://dx.doi.org/10.1126/science.1169588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2943200PMC
April 2009

Identification of single nucleotide polymorphisms in bovine CARD15 and their associations with health and production traits in Canadian Holsteins.

BMC Genomics 2007 Nov 15;8:421. Epub 2007 Nov 15.

Centre for Genetic Improvement of Livestock, Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, N1G 2W1, Canada.

Background: Toll-like receptor-2 (TLR2) and Caspase Recruitment Domain 15 (CARD15) are important pattern recognition receptors that play a role in the initiation of the inflammatory and subsequent immune response. They have been previously identified as susceptibility loci for inflammatory bowel diseases in humans and are, therefore, suitable candidate genes for inflammatory disease resistance in cattle. The objective of this study was to identify single nucleotide polymorphisms (SNPs) in the bovine TLR2 and CARD15 and evaluate the association of these SNPs with health and production traits in a population of Canadian Holstein bulls.

Results: A selective DNA pool was constructed based on the estimated breeding values (EBVs) for SCS. Gene segments were amplified from this pool in PCR reactions and the amplicons sequenced to reveal polymorphisms. A total of four SNPs, including one in intron 10 (c.2886-14A>G) and three in the exon 12 (c.3020A>T, c.4500A>C and c.4950C>T) were identified in CARD15; none were identified in TLR2. Canadian Holstein bulls (n = 338) were genotyped and haplotypes were reconstructed. Two SNPs, c.3020A>T and c.4500A>C, were associated with EBVs for health and production traits. The SNP, c.3020A>T, for example, was associated with SCS EBVs (p = 0.0097) with an allele substitution effect of 0.07 score. When compared to the most frequent haplotype Hap12(AC), Hap22(TC) was associated with increased milk (p < 0.0001) and protein (p = 0.0007) yield EBVs, and hap21(TA) was significantly associated with increased SCS EBV(p = 0.0120). All significant comparison-wise associations retained significance at 8% experimental-wise level by permutation test.

Conclusion: This study indicates that SNP c.3020A>T might play a role in the host response against mastitis and further detailed studies are needed to understand its functional mechanisms.
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http://dx.doi.org/10.1186/1471-2164-8-421DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2234259PMC
November 2007
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