Genome-wide patterns of copy number variation in case-control mastitis study of Polish HF cows using high-density Illumina BovineSNP50 v3 BeadChip array
Keywordsmastitis, cattle, CNV, GWAS, case-control
Background: The mastitis is one of the most important diseases affecting losses of milk yield and functional longevity resulting in economic losses in dairy farms. The cow's inflammation of the mammary gland is a consequence of complex processes in the innate immune system, activation of several cells and accompanying factors that lead to the elimination of microorganism invaders. The study aimed to investigate genetic background by the genome-wide association study (GWAS) for identified copy number variations (CNVs) in one of the most important economically disorders – the mastitis in dairy cattle.
Methods: We investigated 682 Polish-HF cows previously genotyped and analyzed using the following steps: i) identification of CNVs across all the cows based on ARS-UCD1.2 genome map, ii) to perform the GWAS with the utilization of logistic regression models, iii) functional analysis for identified CNVs to indicate putative candidate genes. The cow's genotypes were deposited in the Polish cattle SNP genotypes database (cSNP-db). The phenotype database information covered the veterinary history of mastitis was collected from four experimental farms belonging to the National Institute of Animal Production, Balice, Poland.
Results: Study identified 326 CNVs of which only 28 CNVs were significant with p-value <0.05. The most significant CNVs were identified for BTA17, BTA22, and BTA25, respectively. However, the most interesting from the functional point of view of previously reported CNVs overlapped with genes associated with mastitis were loaded on BTA03 (MSH4), BTA18 (FOXC2, FOXL1, MTHFSD) and BTA27 (TLR3), respectively.
Conclusions: The study clearly concluded that the identification of candidate genes associated with mastitis using of CNVs is feasible. Therefore, one can apply this GWAS approach between the common CNVs and mastitis as a case-control experiment. Our study identified few genes like MSH4, MTHFSD, FOXC2, FOXL1, and TLR3 which were overlapped with tree CNVs to functionally assess and might be considered as the candidate genes for mastitis in Polish HF cattle population. Moreover, obtained results supported by the different genome and transcriptome analysis could lead to a better understood of the genetic background of mastitis.
Brogden KA. Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria? Nat. Rev. Microbiol 2005;3:238–250.
Bierbaum G, Sahl HG. Induction of autolysis of staphylococci by the basic peptide antibiotics pep5 and nisin and their influence on the activity of autolytic enzymes. Arch Microbiol 1985;141:249–254.
Meade K.G, Cormican P, Narciandi F, Lloyd A, O’farrelly C. Bovine -defensin gene family: Opportunities to improve animal health? Physiol. Genomics 2013;46:17–28.
Gurao A, Kashyap SK, Singh R. β-defensins: An innate defense for bovine mastitis. Veterinary World 2017;10:990-998.
Roosen S, Exner K, Paul S, Schroeder J.M, Kalm E, Looft C. Bovine b-defensins: Identification and characterization of novel bovine b-defensin genes and their expression in mammary gland tissue. Mamm. Genome 2004;15:834–842.
Swanson K, Gorodetsky S, Good L, Davis S, Musgrave D, Stelwagen K, Farr V, Molenaar A. Expression of a beta-defensin mRNA, lingual antimicrobial peptide, in bovine mammary epithelial tissue is induced by mastitis. Infect Immunol 2004;72:7311–7314.
Kazuhiro K, Akamatsu H, Obayashi T, Nagahata H, Higuchi H, Iwano H, Oshida T, Yoshimura Y, Isobe N. Relationship between concentration of lingual antimicrobial peptide and somatic cell count in milk of dairy cows. Vet. Immunol Immunopathol 2013;153:298–301.
Kościuczuk EM Lisowski P, Jarczak J, Krzyżewski J, Zwierzchowski L, Bagnicka E. Expression patterns of β-defensin and cathelicidin genes in parenchyma of bovine mammary gland infected with coagulase-positive or coagulase-negative staphylococci. BMC Vet Res 2014;10:1.
Bagnicka E, Strzałkowska N, Szreder T, Prusak B, Jóźwik A, Kosciuczuk E, Krzyzewski J, Zwierzchowski L. A/C polymorphism in the ß-4 defensin gene and its association with phenotypic and breeding values of milk production traits in Polish-Friesian cows. Animal Science Papers and Reports 2008;26:239-250.
Krzyzewski J, Bagnicka E, Strzalkowska N, Jozwik A, Pyzel B, Zwierzchowski L. Association between the polymorphism of bovine beta4-defensin gene and milk traits in Holstein-Friesian cows as computed for standard [305 days] and the whole lactation. Animal Science Papers and Reports 2008;26:191-198.
Zhang F, Gu W, Hurles ME, Lupski JR. Copy number variation in human health, disease, and evolution. Annu Rev Genomics Hum Genet 2009;10:451–481.
Zhou Y, Connor EE, Wiggans GR, et al. Genome-wide copy number variant analysis reveals variants associated with 10 diverse production traits in Holstein cattle. BMC Genomics 2018;19:314.
Zhou Y, Utsunomiya YT, Xu L, Hay EHA, Bickhart DM, Alexandre PA, et al. Genome-wide CNV analysis reveals variants associated with growth traits in Bos indicus. BMC Genomics 2016;17:419.
Xu L, Cole JB, Bickhart DM, Hou Y, Song J, VanRaden PM, et al. Genome wide CNV analysis reveals additional variants associated with milk production traits in Holsteins. BMC Genomics 2014;15:683.
Ben Sassi N, González-Recio Ó, de Paz-del Río R, Rodríguez-Ramilo ST, Fernández AI. Associated effects of copy number variants on economically important traits in Spanish Holstein dairy cattle. J Dairy Sci 2016;99:6371–6380.
Gurgul A, Jasielczuk I, Szmatoła T et al. Genome-wide characteristics of copy number variation in Polish Holstein and Polish Red cattle using SNP genotyping assay. Genetica 2015;143:145–155.
Schnabel, R ARS-UCD1.2 Cow Genome Assembly: Mapping of all existing variants https://www.animalgenome.org/repository/cattle/UMC_bovine_coordinates/ Accessed 11 Sep 2018.
Wang K, Li M, Hadley D, Liu R, Glessner J, Grant S, Hakonarson H, Bucan M. PennCNV: an integrated hidden Markov model designed for high-resolution copy number variation detection in whole-genome SNP genotyping data. Genome Research 2007;17:1665-1674.
Colella S, Yau, C, Taylor JM, Mirza G, Butler H, Clouston, P, Basset AS, Seller A, Holmes C, Ragoussis J. QuantiSNP: an Objective Bayes Hidden-Markov Model to detect and accurately map copy number variation using SNP genotyping data. Nucleic Acids Research 2007;35:2013-2025
Manichaikul A, Mychaleckyj JC, Rich SS, Daly K, Sale M, Chen WM. Robust relationship inference in genome-wide association studies. Bioinformatics 2016;26:2867-2873.
Upadhyay M, Da Silva V H, Megens HJ, Visker MHPW, Ajmone-Marsan P, Bâlteanu VA, Crooijmans RPMA. Distribution and functionality of copy number variation across European cattle populations. Frontiers in Genetics 2017;8:108.
Guttinger M, Sutti F, Panigada M, Porcellini S, Merati B, Mariani M, Grassi F. Epithelial V-like Antigen (EVA), a Novel Member of the Immunoglobulin Superfamily, Expressed in Embryonic Epithelia with a Potential Role as Homotypic Adhesion Molecule in Thymus Histogenesis. The Journal of Cell Biology 1998;141:1061–1071.
Wang H, Wang B, Zhu W, Yang Z. Lentivirus-Mediated Knockdown of Myosin VI Inhibits Cell Proliferation of Breast Cancer Cell. Cancer Biotherapy and Radiopharmaceuticals 2015;30:330–335.
Alvarez-Garcia I, Miska EA. MicroRNA functions in animal development and human disease, Development 2015;132:4653-4662.
Olsen ML, Dilaveri CA Idiopathic granulomatous mastitis: a case report of breast abscess Case Reports 2011;2011:bcr0520114271.
Souza, Fernando & Heinemann, Marcos & Gidlund, Magnus & Blagitz, Maiara & Maria, Alice & Paiva, Melville & Della Libera, Alice Maria & Oliveira, Monica & Cerqueira, Pinho & Reis, Luiza & Ramos Sanchez, Eduardo. (2012). The innate immunity in bovine mastitis: The role of pattern-recognition receptors. American Journal of Immunology 2012;166-178. 10.3844/ajisp.2012.166.178.
Werling, D, Cheng Z. Combining Genome Wide Association Studies and Differential Gene Expression Data Analyses Identifies Candidate Genes Affecting Mastitis Caused by Two Different Pathogens in the Dairy Cow. Open Journal of Animal Sciences 2015;5:358-393.
Kadri NK, Harland C, Faux P, et al. Coding and noncoding variants in HFM1, MLH3, MSH4, MSH5, RNF212, and RNF212B affect recombination rate in cattle. Genome Res 2016;26:1323–1332.
Wawrzykowski J, Franczyk M, Hoedemaker M, Pries M, Streuff B, Kankofer M. Preliminary data on possible protein markers of parturition in cows. Reproduction in Domestic Animals 2017; 53.10.1111/rda.13079.
Goldammer T, Kuehn C, Brunner RM, Weikard R. Evolutionary Break Point Analysis between the Proximal Half of Bovine Chromosome 27 and Conserved Segments of the Human Genome. Cytogenetic and Genome Research 2009;125:33–39.
How to Cite
Title, logo and layout of TR in VS are reserved trademarks of TR in VR.
Number of views and downloads: 184
Number of citations: 0