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PloS one2014; 9(6); e98710; doi: 10.1371/journal.pone.0098710

Identification of genomic loci associated with Rhodococcus equi susceptibility in foals.

Abstract: Pneumonia caused by Rhodococcus equi is a common cause of disease and death in foals. Although agent and environmental factors contribute to the incidence of this disease, the genetic factors influencing the clinical outcomes of R. equi pneumonia are ill-defined. Here, we performed independent single nucleotide polymorphism (SNP)- and copy number variant (CNV)-based genome-wide association studies to identify genomic loci associated with R. equi pneumonia in foals. Foals at a large Quarter Horse breeding farm were categorized into 3 groups: 1) foals with R. equi pneumonia (clinical group [N = 43]); 2) foals with ultrasonographic evidence of pulmonary lesions that never developed clinical signs of pneumonia (subclinical group [N = 156]); and, 3) foals without clinical signs or ultrasonographic evidence of pneumonia (unaffected group [N = 49]). From each group, 24 foals were randomly selected and used for independent SNP- and CNV-based genome-wide association studies (GWAS). The SNP-based GWAS identified a region on chromosome 26 that had moderate evidence of association with R. equi pneumonia when comparing clinical and subclinical foals. A joint analysis including all study foals revealed a 3- to 4-fold increase in odds of disease for a homozygous SNP within the associated region when comparing the clinical group with either of the other 2 groups of foals or their combination. The region contains the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) gene, which is involved in neutrophil function. No associations were identified in the CNV-based GWAS. Collectively, these data identify a region on chromosome 26 associated with R. equi pneumonia in foals, providing evidence that genetic factors may indeed contribute to this important disease of foals.
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Publication Date: 2014-06-03 PubMed ID: 24892408PubMed Central: PMC4043894DOI: 10.1371/journal.pone.0098710Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't
  • Research Support
  • U.S. Gov't
  • Non-P.H.S.

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research is about the genetic factors that may influence susceptibility to Rhodococcus equi pneumonia in foals. The study identified a region on chromosome 26 that is linked to the disease, with particular focus on a gene involved in neutrophil function.

Section 1: Background and Objective of the Research

  • The study focuses on identifying genetic factors that influence susceptibility to Rhodococcus equi pneumonia in foals. Rhodococcus equi is a bacterium that causes pneumonia, a common disease, and cause of death among foals.
  • The objective is to identify genomic loci associated with this disease. Although it is known that both agent and environmental factors contribute to the disease, the genetic factors remain unclear.

Section 2: Methodology

  • The researchers carried out independent genome-wide association studies (GWAS) based on single nucleotide polymorphism (SNP) and copy number variant (CNV).
  • The study was conducted on a large Quarter Horse breeding farm, and foals were put into three categories: foals with R. equi pneumonia (clinical group), foals with evidence of pulmonary disease but no clinical signs of pneumonia (subclinical group), and foals with no signs or evidence of pneumonia (unaffected group).
  • Randomly selected samples from each group were used for the GWAS.

Section 3: Findings

  • The SNP-based GWAS found moderate evidence of a region on chromosome 26 associated with R. equi pneumonia by comparing clinical and subclinical foals. This region houses the TRPM2 gene, which is related to neutrophil function. Neutrophils are white blood cells pivotal in the body’s defense against bacterial infections.
  • When all studies were analyzed together, there was a 3-4 times increase in risk for carrying a homozygous SNP within this region when comparing the clinical group with either the subclinical, unaffected groups, or their combination.
  • By contrast, the CNV-based GWAS did not identify any associations.

Section 4: Conclusion

  • The findings demonstrate a region on chromosome 26 associated with R. equi pneumonia in foals, providing evidence that genetic factors may contribute to this significant disease of foals.

Cite This Article

APA
McQueen CM, Doan R, Dindot SV, Bourquin JR, Zlatev ZZ, Chaffin MK, Blodgett GP, Ivanov I, Cohen ND. (2014). Identification of genomic loci associated with Rhodococcus equi susceptibility in foals. PLoS One, 9(6), e98710. https://doi.org/10.1371/journal.pone.0098710

Publication

PloS one
ISSN: 1932-6203
NlmUniqueID: 101285081
Country: United States
Language: English
Volume: 9
Issue: 6
Pages: e98710

Researcher Affiliations

McQueen, Cole M
  • Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.
Doan, Ryan
  • Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.
Dindot, Scott V
  • Department of Veterinary Pathobiology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America; Department of Molecular and Cellular Medicine, Texas A&M University College of Medicine, College Station, Texas, United States of America.
Bourquin, Jessica R
  • Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.
Zlatev, Zlatomir Z
  • Department of Electrical and Computer Engineering, Texas A&M University Dwight Look College of Engineering, College Station, Texas, United States of America.
Chaffin, M Keith
  • Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.
Blodgett, Glenn P
  • 6666 Ranch, 1102 Dash For Cash Road, Guthrie, Texas, United States of America.
Ivanov, Ivan
  • Department of Veterinary Physiology & Pharmacology, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.
Cohen, Noah D
  • Department of Large Animal Clinical Sciences, Texas A&M University College of Veterinary Medicine & Biomedical Sciences, College Station, Texas, United States of America.

MeSH Terms

  • Animals
  • Disease Susceptibility
  • Genome-Wide Association Study / methods
  • Horse Diseases / genetics
  • Horse Diseases / microbiology
  • Horses
  • Pneumonia, Bacterial / genetics
  • Polymorphism, Single Nucleotide / genetics
  • Rhodococcus equi / pathogenicity

Conflict of Interest Statement

Competing Interests: The authors have declared that no competing interests exist.

References

This article includes 56 references
  1. Halbert ND, Cohen ND, Slovis NM, Faircloth J, Martens RJ. Variations in equid SLC11A1 (NRAMP1) genes and associations with Rhodococcus equi pneumonia in horses.. J Vet Intern Med 20: 974–979.
    pubmed: 16955825
  2. Chaffin MK, Cohen ND, Martens RJ. Evaluation of equine breeding farm characteristics as risk factors for development of Rhodococcus equi pneumonia in foals.. J Am Vet Med Assoc 222: 467–475.
    pubmed: 12597420
  3. Ainsworth DM, Eicker SW, Yeagar AE, Sweeney CR, Viel L. Associations between physical examination, laboratory, and radiographic findings and outcome and subsequent racing performance of foals with Rhodococcus equi infection: 115 cases (1984–1992).. J Am Vet Med Assoc 213: 510–515.
    pubmed: 9713534
  4. Ardans AA, Hietala SK, Spensley MS, Sansome A. Studies of naturally occuring and experimental Rhodococcus equi .. Proc Am Assoc Equine Pract 32: 129–144.
  5. Slovis NM, McCracken JL, Mundy G. How to use thoracic ultrasound to screen foals for Rhodococcus equi at affected farms.. Am Assoc Equine Pract Lexington: pp. 274–278.
  6. Martens RJ, Martens JG, Fiske RA, Hietala SK. Rhodococcus equi foal pneumonia: protective effects of immune plasma in experimentally infected foals.. Equine Vet J 21: 249–255.
    pubmed: 2767025
  7. Horin P, Sabakova K, Futas J, Vychodilova L, Necesankova M. Immunity-related gene single nucleotide polymorphisms associated with Rhodococcus equi infection in foals.. Int J Immunogenet 37: 67–71.
    pubmed: 20002811
  8. Mousel MR, Harrison L, Donahue JM, Bailey E. Rhodococcus equi and genetic susceptibility: assessing transferrin genotypes from paraffin-embedded tissues.. J Vet Diagn Invest 15: 470–472.
    pubmed: 14535549
  9. Signer-Hasler H, Flury C, Haase B, Burger D, Simianer H. A genome-wide association study reveals loci influencing height and other conformation traits in horses.. PLoS One 7: e37282.
    pmc: PMC3353922pubmed: 22615965
  10. Hou Y, Bickhart D, Chung H, Hutchison J, Norman H. Analysis of copy number variations in Holstein cows identify potential mechanisms contributing to differences in residual feed intake.. Funct Integr Genomics 1–7.
    pubmed: 22991089
  11. Corbin LJ, Blott SC, Swinburne JE, Sibbons C, Fox-Clipsham LY. A genome-wide association study of osteochondritis dissecans in the Thoroughbred.. Mamm Genome 23: 294–303.
    pubmed: 22052004
  12. Raudsepp T, McCue ME, Das PJ, Dobson L, Vishnoi M. Genome-wide association study implicates testis-sperm specific FKBP6 as a susceptibility locus for impaired acrosome reaction in stallions.. PLoS Genet 8: e1003139.
    pmc: PMC3527208pubmed: 23284302
  13. Lykkjen S, Dolvik NI, McCue ME, Rendahl AK, Mickelson JR. Equine developmental orthopaedic diseases—a genome-wide association study of first phalanx plantar osteochondral fragments in Standardbred trotters.. Anim Genet 44: 766–769.
    pubmed: 23742657
  14. Petersen JL, Mickelson JR, Rendahl AK, Valberg SJ, Andersson LS. Genome-wide analysis reveals selection for important traits in domestic horse breeds.. PLoS Genet 9: e1003211.
    pmc: PMC3547851pubmed: 23349635
  15. Brosnahan MM, Brooks SA, Antczak DF. Equine clinical genomics: A clinician's primer.. Equine Vet J 42: 658–670.
    pmc: PMC3297474pubmed: 20840582
  16. Graves KT, Henney PJ, Ennis RB. Partial deletion of the LAMA3 gene is responsible for hereditary junctional epidermolysis bullosa in the American Saddlebred Horse.. Anim Genet 40: 35–41.
    pubmed: 19016681
  17. Kato M, Kawaguchi T, Ishikawa S, Umeda T, Nakamichi R. Population-genetic nature of copy number variations in the human genome.. Hum Mol Genet 19: 761–773.
    pmc: PMC2816609pubmed: 19966329
  18. Mills RE, Walter K, Stewart C, Handsaker RE, Chen K. Mapping copy number variation by population-scale genome sequencing.. Nature 470: 59–65.
    pmc: PMC3077050pubmed: 21293372
  19. Carter NP. Methods and strategies for analyzing copy number variation using DNA microarrays.. Nat Genet 39: S16–21.
    pmc: PMC2697494pubmed: 17597776
  20. Metzger J, Philipp U, Lopes MS, da Camara Machado A, Felicetti M. Analysis of copy number variants by three detection algorithms and their association with body size in horses.. BMC Genomics 14: 487.
    pmc: PMC3720552pubmed: 23865711
  21. Dupuis MC, Zhang Z, Durkin K, Charlier C, Lekeux P. Detection of copy number variants in the horse genome and examination of their association with recurrent laryngeal neuropathy.. Anim Genet 44: 206–208.
    pubmed: 22582820
  22. Doan R, Cohen ND, Sawyer J, Ghaffari N, Johnson CD. Whole-genome sequencing and genetic variant analysis of a Quarter Horse mare.. BMC Genomics 13: 78.
    pmc: PMC3309927pubmed: 22340285
  23. Lee T, Cho S, Seo KS, Chang J, Kim H. Genetic variants and signatures of selective sweep of Hanwoo population (Korean native cattle).. BMB Rep 46: 346–351.
    pmc: PMC4133919pubmed: 23884100
  24. Luo J, Yu Y, Mitra A, Chang S, Zhang H. Genome-wide copy number variant analysis in inbred chickens lines with different susceptibility to Marek's disease.. G3 (Bethesda) 3: 217–223.
    pmc: PMC3564982pubmed: 23390598
  25. Hou Y, Liu GE, Bickhart DM, Matukumalli LK, Li C. Genomic regions showing copy number variations associate with resistance or susceptibility to gastrointestinal nematodes in Angus cattle.. Funct Integr Genomics 12: 81–92.
    pubmed: 21928070
  26. Nicholas TJ, Baker C, Eichler EE, Akey JM. A high-resolution integrated map of copy number polymorphisms within and between breeds of the modern domesticated dog.. BMC Genomics 12: 414.
    pmc: PMC3166287pubmed: 21846351
  27. Gokcumen O, Babb PL, Iskow RC, Zhu Q, Shi X. Refinement of primate copy number variation hotspots identifies candidate genomic regions evolving under positive selection.. Genome Biol 12: R52.
    pmc: PMC3219974pubmed: 21627829
  28. Liu GE, Brown T, Hebert DA, Cardone MF, Hou Y. Initial analysis of copy number variations in cattle selected for resistance or susceptibility to intestinal nematodes.. Mamm Genome 22: 111–121.
    pubmed: 21125402
  29. Liu GE, Hou Y, Zhu B, Cardone MF, Jiang L. Analysis of copy number variations among diverse cattle breeds.. Genome Res 20: 693–703.
    pmc: PMC2860171pubmed: 20212021
  30. Nicholas TJ, Cheng Z, Ventura M, Mealey K, Eichler EE. The genomic architecture of segmental duplications and associated copy number variants in dogs.. Genome Res 19: 491–499.
    pmc: PMC2661811pubmed: 19129542
  31. Giguère S, Cohen ND, Keith Chaffin M, Slovis NM, Hondalus MK. Diagnosis, Treatment, Control, and Prevention of Infections Caused by Rhodococcus equi in Foals.. J Vet Intern Med 25: 1209–1220.
    pubmed: 22092608
  32. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA. PLINK: a tool set for whole-genome association and population-based linkage analyses.. Am J Hum Genet 81: 559–575.
    pmc: PMC1950838pubmed: 17701901
  33. Lykkjen S, Dolvik NI, McCue ME, Rendahl AK, Mickelson JR. Genome-wide association analysis of osteochondrosis of the tibiotarsal joint in Norwegian Standardbred trotters.. Anim Genet 41 Suppl 2 111–120.
    pubmed: 21070284
  34. Consotium WTCC. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls.. Nature 447: 661–678.
    pmc: PMC2719288pubmed: 17554300
  35. Aulchenko YS, Ripke S, Isaacs A, van Duijn CM. GenABEL: an R library for genome-wide association analysis.. Bioinformatics 23: 1294–1296.
    pubmed: 17384015
  36. Vazquez AI, Bates DM, Rosa GJ, Gianola D, Weigel KA. Technical note: an R package for fitting generalized linear mixed models in animal breeding.. J Anim Sci 88: 497–504.
    pubmed: 19820058
  37. Price AL, Zaitlen NA, Reich D, Patterson N. New approaches to population stratification in genome-wide association studies.. Nat Rev Genet 11: 459–463.
    pmc: PMC2975875pubmed: 20548291
  38. Edgar R, Domrachev M, Lash AE. Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.. Nucleic Acids Res 30: 207–210.
    pmc: PMC99122pubmed: 11752295
  39. Ye S, Dhillon S, Ke X, Collins AR, Day IN. An efficient procedure for genotyping single nucleotide polymorphisms.. Nucleic Acids Res 29: E88–88.
    pmc: PMC55900pubmed: 11522844
  40. Untergasser A, Cutcutache I, Koressaar T, Ye J, Faircloth BC. Primer3—new capabilities and interfaces.. Nucleic Acids Res 40: e115.
    pmc: PMC3424584pubmed: 22730293
  41. Doan R, Cohen N, Harrington J, Veazy K, Juras R. Identification of copy number variants in horses.. Genome Res 22: 899–907.
    pmc: PMC3337435pubmed: 22383489
  42. Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance.. Biometrika 75: 800–802.
  43. Yamamoto S, Shimizu S, Kiyonaka S, Takahashi N, Wajima T. TRPM2-mediated Ca2+influx induces chemokine production in monocytes that aggravates inflammatory neutrophil infiltration.. Nat Med 14: 738–747.
    pmc: PMC2789807pubmed: 18542050
  44. Giguere S, Cohen ND, Chaffin MK, Hines SA, Hondalus MK. Rhodococcus equi: clinical manifestations, virulence, and immunity.. J Vet Intern Med 25: 1221–1230.
    pubmed: 22092609
  45. Cohen ND, Kuskie KR, Smith JL, Slovis NM, Brown SE 2nd. Association of airborne concentration of virulent Rhodococcus equi with location (stall versus paddock) and month (January through June) on 30 horse breeding farms in central Kentucky.. Am J Vet Res 73: 1603–1609.
    pubmed: 23013187
  46. Dawson TRMY, Horohov DW, Meijer WG, Muscatello G. Current understanding of the equine immune response to Rhodococcus equi. An immunological review of R. equi pneumonia.. Vet Immunol Immunopathol 135: 1–11.
    pubmed: 20064668
  47. Heller MC, Jackson KA, Watson JL. Identification of immunologically relevant genes in mare and foal dendritic cells responding to infection by Rhodococcus equi.. Vet Immunol Immunopathol 136: 144–150.
    pubmed: 20334935
  48. Martens RJ, Cohen ND, Jones SL, Moore TA, Edwards JF. Protective role of neutrophils in mice experimentally infected with Rhodococcus equi.. Infect Immun 73: 7040–7042.
    pmc: PMC1230988pubmed: 16177388
  49. Chaffin MK, Cohen ND, Martens RJ, Edwards RF, Nevill M. Hematologic and immunophenotypic factors associated with development of Rhodococcus equi pneumonia of foals at equine breeding farms with endemic infection.. Vet Immunol Immunopathol 100: 33–48.
    pubmed: 15182994
  50. Tateda K, Moore TA, Newstead MW, Tsai WC, Zeng X. Chemokine-dependent neutrophil recruitment in a murine model of Legionella pneumonia: potential role of neutrophils as immunoregulatory cells.. Infect Immun 69: 2017–2024.
    pmc: PMC98125pubmed: 11254553
  51. Lyons MJ, Yoshimura T, McMurray DN. Interleukin (IL)-8 (CXCL8) induces cytokine expression and superoxide formation by guinea pig neutrophils infected with Mycobacterium tuberculosis.. Tuberculosis (Edinb) 84: 283–292.
    pubmed: 15207803
  52. Bordin AI, Liu M, Nerren JR, Buntain SL, Brake CN. Neutrophil function of neonatal foals is enhanced in vitro by CpG oligodeoxynucleotide stimulation.. Vet Immunol Immunopathol 145: 290–297.
    pubmed: 22197007
  53. Nerren JR, Martens RJ, Payne S, Murrell J, Butler JL. Age-related changes in cytokine expression by neutrophils of foals stimulated with virulent Rhodococcus equi in vitro.. Vet Immunol Immunopathol 127: 212–219.
    pubmed: 19026456
  54. Liu M, Liu T, Bordin A, Nerren J, Cohen N. Activation of foal neutrophils at different ages by CpG oligodeoxynucleotides and Rhodococcus equi.. Cytokine 48: 280–289.
    pubmed: 19819162
  55. Ackermann M. Acute Inflamation.. Pathologic Basis of Veterinary Disease 4 ed. pp. 120.
  56. Zhang W, Chu X, Tong Q, Cheung JY, Conrad K. A novel TRPM2 isoform inhibits calcium influx and susceptibility to cell death.. J Biol Chem 278: 16222–16229.
    pubmed: 12594222

Citations

This article has been cited 6 times.
  1. Sharma NK, Singh P, Saha B, Bhardwaj A, Iquebal MA, Pal Y, Nayan V, Jaiswal S, Giri SK, Legha RA, Bhattacharya TK, Kumar D, Rai A. Genome wide landscaping of copy number variations for horse inter-breed variability. Anim Biotechnol 2025 Dec;36(1):2446251.
    doi: 10.1080/10495398.2024.2446251pubmed: 39791493google scholar: lookup
  2. da Silveira BP, Cohen ND, Lawhon SD, Watson RO, Bordin AI. Protective immune response against Rhodococcus equi: An innate immunity-focused review. Equine Vet J 2025 May;57(3):563-586.
    doi: 10.1111/evj.14214pubmed: 39258739google scholar: lookup
  3. Schurink A, da Silva VH, Velie BD, Dibbits BW, Crooijmans RPMA, Franҫois L, Janssens S, Stinckens A, Blott S, Buys N, Lindgren G, Ducro BJ. Copy number variations in Friesian horses and genetic risk factors for insect bite hypersensitivity. BMC Genet 2018 Jul 30;19(1):49.
    doi: 10.1186/s12863-018-0657-0pubmed: 30060732google scholar: lookup
  4. McQueen CM, Whitfield-Cargile CM, Konganti K, Blodgett GP, Dindot SV, Cohen ND. TRPM2 SNP genotype previously associated with susceptibility to Rhodococcus equi pneumonia in Quarter Horse foals displays differential gene expression identified using RNA-Seq. BMC Genomics 2016 Dec 5;17(1):993.
    doi: 10.1186/s12864-016-3345-3pubmed: 27919223google scholar: lookup
  5. Rocha JN, Cohen ND, Bordin AI, Brake CN, Giguère S, Coleman MC, Alaniz RC, Lawhon SD, Mwangi W, Pillai SD. Oral Administration of Electron-Beam Inactivated Rhodococcus equi Failed to Protect Foals against Intrabronchial Infection with Live, Virulent R. equi. PLoS One 2016;11(2):e0148111.
    doi: 10.1371/journal.pone.0148111pubmed: 26828865google scholar: lookup
  6. McQueen CM, Dindot SV, Foster MJ, Cohen ND. Genetic Susceptibility to Rhodococcus equi. J Vet Intern Med 2015 Nov-Dec;29(6):1648-59.
    doi: 10.1111/jvim.13616pubmed: 26340305google scholar: lookup
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