Genome-wide association study identifies loci associated with milk leukocyte phenotypes following experimental challenge with Streptococcus uberis
- 144 Downloads
Mastitis is a detrimental disease in the dairy industry that decreases milk quality and costs upwards of $2 billion annually. Often, mastitis results from bacteria entering the gland through the teat opening. Streptococcus uberis is responsible for a high percentage of subclinical and clinical mastitis. Following an intramammary experimental challenge with S. uberis on Holstein cows (n = 40), milk samples were collected and somatic cell counts (SCC) were determined by the Dairy Herd Improvement Association Laboratory. Traditional genome-wide association studies (GWAS) have utilized test day SCC or SCC lactation averages to identify loci of interest. Our approach utilizes SCC collected following a S. uberis experimental challenge to generate three novel phenotypes: (1) area under the curve (AUC) of SCC for 0–7 days and (2) 0–28 days post-challenge; and (3) when SCC returned to below 200,000 cells/mL post-challenge (< 21 days, 21–28 days, or > 28 days). Polymorphisms were identified using Illumina’s BovineSNP50 v2 DNA BeadChip. Associations were tested using Plink software and identified 16 significant (p < 1.0 × 10−4) single-nucleotide polymorphisms (SNPs) across the phenotypes. Most significant SNPs were in genes linked to cell signaling, migration, and apoptosis. Several have been recognized in relation to infectious processes (ATF7, SGK1, and PACRG), but others less so (TRIO, GLRA1, CELSR2, TIAM2, CPE). Further investigation of these genes and their roles in inflammation (e.g., SCC) can provide potential targets that influence resolution of mammary gland infection. Likewise, further investigation of the identified SNP with mastitis and other disease phenotypes can provide greater insight to the potential of these SNP as genetic markers.
KeywordsMastitis Genetics GWAS S. uberis Candidate genes Post-partum
The authors would like to thank Dr. Arnold Saxton of the department of Animal Science at the University of Tennessee for his assistance in converting the data format. A special thank you to the staff at the East Tennessee Research and Education Center Little River Unit for their aid in animal care and milking.
The challenge portion of this study was supported by USDA-NIFA-AFRI (2011-67015-30168). The remaining portions of the study were supported by UTAgResearch and the AgInnovation fund.
- Cole JB, Wiggans GR, Ma L, Sonstegard TS, Lawlor TJ Jr, Crooker BA et al (2011) Genome-wide association analysis of thirty one production, health, reproduction and body conformation traits in contemporary U.S. Holstein cows. BMC Genomics 12:408. https://doi.org/10.1186/1471-2164-12-408 CrossRefPubMedPubMedCentralGoogle Scholar
- Croft D, Mundo AF, Haw R, Milacic M, Weiser J, Wu G, Caudy M, Garapati P, Gillespie M, Kamdar MR, Jassal B, Jupe S, Matthews L, May B, Palatnik S, Rothfels K, Shamovsky V, Song H, Williams M, Birney E, Hermjakob H, Stein L, D'Eustachio P (2014) The Reactome pathway knowledgebase. Nucleic Acids Res 42:D472–D477CrossRefPubMedGoogle Scholar
- Fabregat A, Jupe S, Matthews L, Sidiropoulos K, Gillespie M, Garapati P, Haw R, Jassal B, Korninger F, May B, Milacic M, Roca CD, Rothfels K, Sevilla C, Shamovsky V, Shorser S, Varusai T, Viteri G, Weiser J, Wu G, Stein L, Hermjakob H, D’Eustachio P (2018) The reactome pathway knowledgebase. Nucleic Acids Res 46:D649–D655CrossRefPubMedGoogle Scholar
- Pérez-Cabal MA, Charfeddine N (2013) Genetic relationship between clinical mastitis and several traits of interest in Spanish Holstein dairy cattle. Interbull Bulletin 47:77–81Google Scholar
- Pighetti GM et al. (2017) Vaccination with recombinant Streptococcus uberis Adhesion Molecule alters immune response to experimental challenge. Int J Vet Dairy Sci. Published online: 05/15/2017Google Scholar
- Ryman VE, Packiriswamy N, Sordillo LM (2016) Apoptosis of endothelial cells by 13-HPODE contributes to impairment of endothelial barrier integrity. Med Inflammation 2016:13. https://doi.org/10.1155/2016/9867138
- Schukken YH, Günther J, Fitzpatrick J, Fontaine MC, Goetze L, Holst O, Leigh J, Petzl W, Schuberth HJ, Sipka A, Smith DGE, Quesnell R, Watts J, Yancey R, Zerbe H, Gurjar A, Zadoks RN, Seyfert HM (2011) Host-response patterns of intramammary infections in dairy cows. Vet Immunol Immunopathol 144:270–289CrossRefPubMedGoogle Scholar
- Yoshida K, Maekawa T, Zhu Y, Renard-Guillet C, Chatton B, Inoue K, Uchiyama T, Ishibashi KI, Yamada T, Ohno N, Shirahige K, Okada-Hatakeyama M, Ishii S (2015) The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory. Nat Immunol 16:1034–1043CrossRefPubMedGoogle Scholar
- Zadoks RN (2007) Sources and epidemiology of Streptococcus uberis, with special emphasis on mastitis in dairy cattle. Perspectives in Agriculture, Veterinary Science, Nutrition and Natural Resources 2:15Google Scholar