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ARS Home » Northeast Area » Beltsville, Maryland (BARC) » Beltsville Agricultural Research Center » Animal Genomics and Improvement Laboratory » Research » Publications at this Location » Publication #308097
Title: A genome-wide association study for clinical mastitis in first parity US Holstein cows using a single-step approach and a genomic matrix re-weighting procedure

Author
item TIEZZI, FRANCESCO - North Carolina State University
item PARKER GADDIS, KRISTEN - North Carolina State University
item Cole, John
item CLAY, JOHN - Dairy Records Management Systems(DRMS)
item MALTECCA, CHRISTIAN - North Carolina State University

Submitted to: PLOS ONE
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/1/2014
Publication Date: 2/6/2015
Publication URL: http://handle.nal.usda.gov/10113/60898
Citation: Tiezzi, F., Parker Gaddis, K.L., Cole, J.B., Clay, J.S., Maltecca, C. 2015. A genome-wide association study for clinical mastitis in first parity US Holstein cows using a single-step approach and genomic matrix re-weighting procedure. PLoS One. 10(2):e0114919.

Interpretive Summary: Mastitis, an infection of the mammary gland, is the most costly health problem affecting US dairy farmers. Information about the occurrence of clinical mastitis is not routinely recorded in a national database, but it is available in on-farm computer systems used by farmers for herd management purposes. Data for more than 100,000 first-lactation Holstein cows were used in a scan to identify regions of the genome that are involved in the regulation of immune responses to infection. Genes located on chromosomes 1, 14, and 20 appear to be involved in resistance to infections of the mammary gland in Holstein cows.

Technical Abstract: Clinical mastitis (CM) is one of the health disorders with largest impacts on dairy farming profitability and animal welfare. Previous studies have consistently shown that CM is under genetic control but knowledge about regions of the genome associated with resistance to CM in US Holstein is lacking. The objective of this study was to perform a genome-wide association study (GWAS) for CM in first-lactation Holstein cows and identify SNPs associated with genes that have large effects on resistance to udder infection. Producer-recorded mastitis event information for 103,585 first-lactation cows were used for this purpose, together with genotype information on 1,361 bulls from the Illumina BovineSNP50 BeadChip. Single-step genomic-BLUP methodology was used to incorporate genomic data into a threshold-liability model. Association analysis confirmed that CM follows a highly polygenic mode of inheritance. However, 10-adjacent-SNP windows showed that regions on chromosomes 2, 14 and 20 have impacts on genetic variation for CM and contain genes related to immune response, which represent putative QTLs. On chromosome 14, six genes (LY6K, LY6D, LYNX1, LYPD2, SLURP1, and PSCA) were located in proximity to the window with highest variance. These genes are part of the lymphocyte-antigen-6 complex (LY6) known for its neutrophils regulation function linked to the major histocompatibility complex. Other genes on chromosome 2 were also involved in regulating immune response (IFIH1, LY75, and DPP4), or are themselves regulated in the presence of specific pathogens (ITGB6, NR4A2). Other genes annotated on chromosome 20 are involved in mammary gland metabolism (GHR, OXCT1), antibody production and phagocytosis of bacterial cells (C6, C7, C9, C1QTNF3), tumor suppression (DAB2), involution of mammary epithelium (OSMR) and cytokine regulation (PRLR). DAVID enrichment analysis revealed 5 KEGG pathways that contained the aforementioned genes, 4 of which were linked to immune response. The JAK-STAT signaling pathway (cell proliferation and apoptosis) and the ‘Cytokine-cytokine receptor interaction’ (cytokine and interleukines response to infectious agents) are co-regulated and linked to the ‘ABC transporters’ pathway also found here. Gene network analysis performed using GeneMania revealed a co-expression network where 665 interactions existed among 145 of the genes reported above. Clinical mastitis is a complex trait, and the different genes regulating immune response are known to be pathogen-specific. Despite the lack of pathogen information in this study, candidate QTL for CM were identified in the US Holstein population.