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Genome-wide association study identifies loci associated with milk leukocyte phenotypes following experimental challenge with Streptococcus uberis

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Abstract

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.

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Acknowledgements

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.

Funding

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.

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Authors and Affiliations

  1. Department of Animal Science, The University of Tennessee, 2506 River Drive, Knoxville, TN, 37996, USA

    Lydia Siebert, Susan Headrick, Mark Lewis, Barbara Gillespie, Raul A. Almeida, Stephen P. Oliver & Gina M. Pighetti

  2. Department of Entomology and Plant Pathology, The University of Tennessee, 2431 Joe Johnson Drive, Knoxville, TN, 37996, USA

    Margaret E. Staton

  3. Zoetis, 100 Campus Drive, Florham Park, NJ, 07932, USA

    Charles Young

  4. AgResearch, The University of Tennessee, 2621 Morgan Circle, Knoxville, TN, 37996, USA

    Stephen P. Oliver

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  1. Lydia Siebert
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Correspondence to Gina M. Pighetti.

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Siebert, L., Staton, M.E., Headrick, S. et al. Genome-wide association study identifies loci associated with milk leukocyte phenotypes following experimental challenge with Streptococcus uberis. Immunogenetics 70, 553–562 (2018). https://doi.org/10.1007/s00251-018-1065-3

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