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A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions.

Abstract: Recurrent airway obstruction (RAO), or heaves, is a naturally occurring asthma-like disease that is related to sensitisation and exposure to mouldy hay and has a familial basis with a complex mode of inheritance. A genome-wide scanning approach using two half-sibling families was taken in order to locate the chromosome regions that contribute to the inherited component of this condition in these families. Initially, a panel of 250 microsatellite markers, which were chosen as a well-spaced, polymorphic selection covering the 31 equine autosomes, was used to genotype the two half-sibling families, which comprised in total 239 Warmblood horses. Subsequently, supplementary markers were added for a total of 315 genotyped markers. Each half-sibling family is focused around a severely RAO-affected stallion, and the phenotype of each individual was assessed for RAO and related signs, namely, breathing effort at rest, breathing effort at work, coughing, and nasal discharge, using an owner-based questionnaire. Analysis using a regression method for half-sibling family structures was performed using RAO and each of the composite clinical signs separately; two chromosome regions (on ECA13 and ECA15) showed a genome-wide significant association with RAO at P < 0.05. An additional 11 chromosome regions showed a more modest association. This is the first publication that describes the mapping of genetic loci involved in RAO. Several candidate genes are located in these regions, a number of which are interleukins. These are important signalling molecules that are intricately involved in the control of the immune response and are therefore good positional candidates.
Publication Date: 2009-09-18 PubMed ID: 19760324DOI: 10.1007/s00335-009-9214-5Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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The research in this article investigates the genetic origins of recurrent airway obstruction (RAO) in Warmblood sport horses, identifying two significant chromosome regions potentially linked to the disease.

Study Background and Objective

  • This research focuses on Recurrent Airway Obstruction (RAO), a health condition in Warmblood sport horses similar to asthma in humans. This disease is related to exposure to mouldy hay and has a genetic basis with a complex inheritance pattern.
  • The study aims to identify the chromosomal regions associated with the inherited component of RAO using a genome-wide scanning technique.

Research Methodology

  • The researchers used two half-sibling Warmblood families for their study, centering on a severely RAO-impacted stallion in each family.
  • Initially, the researchers genotyped these families using a panel of 250 microsatellite markers. These markers provided a wide and varied coverage of the 31 equine autosomes.
  • The study later added extra markers, leading to a total of 315 genotyped markers.
  • The researchers assessed the severity of RAO symptoms in each individual horse through an owner-based questionnaire. Symptoms considered included breathing difficulty at rest or during work, coughing, and nasal discharge.
  • A regression method was employed to analyze the RAO symptoms and the genotypic structures of the half-sibling families.

Results

  • The results highlight two chromosomal regions, on ECA13 and ECA15, significantly associated with RAO.
  • 11 other chromosomal regions showed a possible but less pronounced relationship.
  • This study is the first to scientifically map the genetic loci involved in RAO.

Implications and Conclusions

  • The identified regions contain several candidate genes for RAO, including a number of interleukins, which are vital to controlling immune responses.
  • The findings can help understand the genetic basis of RAO and pave the way for further studies and potential treatments.

Cite This Article

APA
Swinburne JE, Bogle H, Klukowska-Rötzler J, Drögemüller M, Leeb T, Temperton E, Dolf G, Gerber V. (2009). A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions. Mamm Genome, 20(8), 504-515. https://doi.org/10.1007/s00335-009-9214-5

Publication

ISSN: 1432-1777
NlmUniqueID: 9100916
Country: United States
Language: English
Volume: 20
Issue: 8
Pages: 504-515

Researcher Affiliations

Swinburne, June E
  • Animal Health Trust, Newmarket, Suffolk CB8 7UU, UK. june.swinburne@aht.org.uk
Bogle, Helen
    Klukowska-Rötzler, Jolanta
      Drögemüller, Michaela
        Leeb, Tosso
          Temperton, Elizabeth
            Dolf, Gaudenz
              Gerber, Vincent

                MeSH Terms

                • Airway Obstruction / genetics
                • Airway Obstruction / veterinary
                • Animals
                • Chromosome Mapping
                • Female
                • Genetic Linkage
                • Genome-Wide Association Study / veterinary
                • Horse Diseases / genetics
                • Horses
                • Male
                • Pedigree
                • Quantitative Trait Loci

                References

                This article includes 40 references
                1. Kim SH, Kim YK, Park HW, Jee YK, Kim SH, Bahn JW, Chang YS, Kim SH, Ye YM, Shin ES, Lee JE, Park HS, Min KU. Association between polymorphisms in prostanoid receptor genes and aspirin-intolerant asthma.. Pharmacogenet Genomics 2007 Apr;17(4):295-304.
                2. Malerba G, Pignatti PF. A review of asthma genetics: gene expression studies and recent candidates.. J Appl Genet 2005;46(1):93-104.
                  pubmed: 15741670
                3. Schuelke M. An economic method for the fluorescent labeling of PCR fragments.. Nat Biotechnol 2000 Feb;18(2):233-4.
                  pubmed: 10657137doi: 10.1038/72708google scholar: lookup
                4. Howard TD, Koppelman GH, Xu J, Zheng SL, Postma DS, Meyers DA, Bleecker ER. Gene-gene interaction in asthma: IL4RA and IL13 in a Dutch population with asthma.. Am J Hum Genet 2002 Jan;70(1):230-6.
                  pubmed: 11709756doi: 10.1086/338242google scholar: lookup
                5. Rogaev EI, Sherrington R, Rogaeva EA, Levesque G, Ikeda M, Liang Y, Chi H, Lin C, Holman K, Tsuda T. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene.. Nature 1995 Aug 31;376(6543):775-8.
                  pubmed: 7651536doi: 10.1038/376775a0google scholar: lookup
                6. Koppelman GH, te Meerman GJ, Postma DS. Genetic testing for asthma.. Eur Respir J 2008 Sep;32(3):775-82.
                  pubmed: 18757702doi: 10.1183/09031936.00093608google scholar: lookup
                7. Abecasis GR, Cherny SS, Cookson WO, Cardon LR. Merlin--rapid analysis of dense genetic maps using sparse gene flow trees.. Nat Genet 2002 Jan;30(1):97-101.
                  pubmed: 11731797doi: 10.1038/ng786google scholar: lookup
                8. Robinson NE, Derksen FJ, Olszewski MA, Buechner-Maxwell VA. The pathogenesis of chronic obstructive pulmonary disease of horses.. Br Vet J 1996 May;152(3):283-306.
                  pubmed: 8762605doi: 10.1016/s0007-1935(96)80101-1google scholar: lookup
                9. Whittaker PA. Genes for asthma: much ado about nothing?. Curr Opin Pharmacol 2003 Jun;3(3):212-9.
                  pubmed: 12810182doi: 10.1016/s1471-4892(03)00035-3google scholar: lookup
                10. Wills-Karp M, Ewart SL. Time to draw breath: asthma-susceptibility genes are identified.. Nat Rev Genet 2004 May;5(5):376-87.
                  pubmed: 15143320doi: 10.1038/nrg1326google scholar: lookup
                11. Eder C, Crameri R, Mayer C, Eicher R, Straub R, Gerber H, Lazary S, Marti E. Allergen-specific IgE levels against crude mould and storage mite extracts and recombinant mould allergens in sera from horses affected with chronic bronchitis.. Vet Immunol Immunopathol 2000 Mar 15;73(3-4):241-53.
                  pubmed: 10713338doi: 10.1016/s0165-2427(00)00154-9google scholar: lookup
                12. Cui T, Wu J, Pan S, Xie J. Polymorphisms in the IL-4 and IL-4R [alpha] genes and allergic asthma.. Clin Chem Lab Med 2003 Jul;41(7):888-92.
                  pubmed: 12940513doi: 10.1515/CCLM.2003.134google scholar: lookup
                13. Hytönen AM, Löwhagen O, Arvidsson M, Balder B, Björk AL, Lindgren S, Hahn-Zoric M, Hanson LA, Padyukov L. Haplotypes of the interleukin-4 receptor alpha chain gene associate with susceptibility to and severity of atopic asthma.. Clin Exp Allergy 2004 Oct;34(10):1570-5.
                14. Kurucz I, Szelenyi I. Current animal models of bronchial asthma.. Curr Pharm Des 2006;12(25):3175-94.
                  pubmed: 17020527doi: 10.2174/138161206778194169google scholar: lookup
                15. Shamim Z, Müller K, Svejgaard A, Poulsen LK, Bodtger U, Ryder LP. Association between genetic polymorphisms in the human interleukin-7 receptor alpha-chain and inhalation allergy.. Int J Immunogenet 2007 Jun;34(3):149-51.
                16. Seaton G, Haley CS, Knott SA, Kearsey M, Visscher PM. QTL Express: mapping quantitative trait loci in simple and complex pedigrees.. Bioinformatics 2002 Feb;18(2):339-40.
                17. Chae SC, Li CS, Kim KM, Yang JY, Zhang Q, Lee YC, Yang YS, Chung HT. Identification of polymorphisms in human interleukin-27 and their association with asthma in a Korean population.. J Hum Genet 2007;52(4):355-361.
                  pubmed: 17318299doi: 10.1007/s10038-007-0123-8google scholar: lookup
                18. Vendelin J, Pulkkinen V, Rehn M, Pirskanen A, Räisänen-Sokolowski A, Laitinen A, Laitinen LA, Kere J, Laitinen T. Characterization of GPRA, a novel G protein-coupled receptor related to asthma.. Am J Respir Cell Mol Biol 2005 Sep;33(3):262-70.
                  pubmed: 15947423doi: 10.1165/rcmb.2004-0405OCgoogle scholar: lookup
                19. Hansen G, Jin S, Umetsu DT, Conti M. Absence of muscarinic cholinergic airway responses in mice deficient in the cyclic nucleotide phosphodiesterase PDE4D.. Proc Natl Acad Sci U S A 2000 Jun 6;97(12):6751-6.
                  pubmed: 10841571doi: 10.1073/pnas.97.12.6751google scholar: lookup
                20. Kurz T, Hoffjan S, Hayes MG, Schneider D, Nicolae R, Heinzmann A, Jerkic SP, Parry R, Cox NJ, Deichmann KA, Ober C. Fine mapping and positional candidate studies on chromosome 5p13 identify multiple asthma susceptibility loci.. J Allergy Clin Immunol 2006 Aug;118(2):396-402.
                  pubmed: 16890764doi: 10.1016/j.jaci.2006.04.036google scholar: lookup
                21. Abdulamir AS, Hafidh RR, Abubakar F, Abbas KA. Changing survival, memory cell compartment, and T-helper balance of lymphocytes between severe and mild asthma.. BMC Immunol 2008 Dec 16;9:73.
                  pubmed: 19087256doi: 10.1186/1471-2172-9-73google scholar: lookup
                22. Lavoie JP, Maghni K, Desnoyers M, Taha R, Martin JG, Hamid QA. Neutrophilic airway inflammation in horses with heaves is characterized by a Th2-type cytokine profile.. Am J Respir Crit Care Med 2001 Oct 15;164(8 Pt 1):1410-3.
                  pubmed: 11704587doi: 10.1164/ajrccm.164.8.2012091google scholar: lookup
                23. Mitsuyasu H, Izuhara K, Mao XQ, Gao PS, Arinobu Y, Enomoto T, Kawai M, Sasaki S, Dake Y, Hamasaki N, Shirakawa T, Hopkin JM. Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma.. Nat Genet 1998 Jun;19(2):119-20.
                  pubmed: 9620765doi: 10.1038/472google scholar: lookup
                24. Gerber V, Straub R, Marti E, Hauptman J, Herholz C, King M, Imhof A, Tahon L, Robinson NE. Endoscopic scoring of mucus quantity and quality: observer and horse variance and relationship to inflammation, mucus viscoelasticity and volume.. Equine Vet J 2004 Nov;36(7):576-82.
                  pubmed: 15581321doi: 10.2746/0425164044864525google scholar: lookup
                25. Cottingham RW Jr, Idury RM, Schäffer AA. Faster sequential genetic linkage computations.. Am J Hum Genet 1993 Jul;53(1):252-63.
                  pubmed: 8317490
                26. Williams JT, Blangero J. Power of variance component linkage analysis to detect quantitative trait loci.. Ann Hum Genet 1999 Nov;63(Pt 6):545-63.
                  pubmed: 11246457doi: 10.1017/S0003480099007848google scholar: lookup
                27. Bossé Y, Hudson TJ. Toward a comprehensive set of asthma susceptibility genes.. Annu Rev Med 2007;58:171-84.
                28. Hecker M, Bohnert A, König IR, Bein G, Hackstein H. Novel genetic variation of human interleukin-21 receptor is associated with elevated IgE levels in females.. Genes Immun 2003 Apr;4(3):228-33.
                  pubmed: 12700598doi: 10.1038/sj.gene.6363954google scholar: lookup
                29. Inoue H, Fukuyama S, Matsumoto K, Kubo M, Yoshimura A. Role of endogenous inhibitors of cytokine signaling in allergic asthma.. Curr Med Chem 2007;14(2):181-9.
                  pubmed: 17266577doi: 10.2174/092986707779313327google scholar: lookup
                30. Herszberg B, Ramos-Barbón D, Tamaoka M, Martin JG, Lavoie JP. Heaves, an asthma-like equine disease, involves airway smooth muscle remodeling.. J Allergy Clin Immunol 2006 Aug;118(2):382-8.
                  pubmed: 16890762doi: 10.1016/j.jaci.2006.03.044google scholar: lookup
                31. Kroegel C, Foerster M. Phosphodiesterase-4 inhibitors as a novel approach for the treatment of respiratory disease: cilomilast.. Expert Opin Investig Drugs 2007 Jan;16(1):109-24.
                  pubmed: 17155857doi: 10.1517/13543784.16.1.109google scholar: lookup
                32. Ober C, Leavitt SA, Tsalenko A, Howard TD, Hoki DM, Daniel R, Newman DL, Wu X, Parry R, Lester LA, Solway J, Blumenthal M, King RA, Xu J, Meyers DA, Bleecker ER, Cox NJ. Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations.. Am J Hum Genet 2000 Feb;66(2):517-26.
                  pubmed: 10677312doi: 10.1086/302781google scholar: lookup
                33. Giguère S, Viel L, Lee E, MacKay RJ, Hernandez J, Franchini M. Cytokine induction in pulmonary airways of horses with heaves and effect of therapy with inhaled fluticasone propionate.. Vet Immunol Immunopathol 2002 Mar;85(3-4):147-58.
                  pubmed: 11943316doi: 10.1016/s0165-2427(01)00420-2google scholar: lookup
                34. Ramseyer A, Gaillard C, Burger D, Straub R, Jost U, Boog C, Marti E, Gerber V. Effects of genetic and environmental factors on chronic lower airway disease in horses.. J Vet Intern Med 2007 Jan-Feb;21(1):149-56.
                35. Gerber V, Baleri D, Klukowska-Rötzler J, Swinburne JE, Dolf G. Mixed inheritance of equine recurrent airway obstruction.. J Vet Intern Med 2009 May-Jun;23(3):626-30.
                36. Swinburne JE, Boursnell M, Hill G, Pettitt L, Allen T, Chowdhary B, Hasegawa T, Kurosawa M, Leeb T, Mashima S, Mickelson JR, Raudsepp T, Tozaki T, Binns M. Single linkage group per chromosome genetic linkage map for the horse, based on two three-generation, full-sibling, crossbred horse reference families.. Genomics 2006 Jan;87(1):1-29.
                  pubmed: 16314071doi: 10.1016/j.ygeno.2005.09.001google scholar: lookup
                37. Ainsworth DM, Grünig G, Matychak MB, Young J, Wagner B, Erb HN, Antczak DF. Recurrent airway obstruction (RAO) in horses is characterized by IFN-gamma and IL-8 production in bronchoalveolar lavage cells.. Vet Immunol Immunopathol 2003 Nov 15;96(1-2):83-91.
                  pubmed: 14522137doi: 10.1016/s0165-2427(03)00142-9google scholar: lookup
                38. Horohov DW, Beadle RE, Mouch S, Pourciau SS. Temporal regulation of cytokine mRNA expression in equine recurrent airway obstruction.. Vet Immunol Immunopathol 2005 Oct 18;108(1-2):237-45.
                  pubmed: 16098607doi: 10.1016/j.vetimm.2005.07.013google scholar: lookup
                39. Marti E, Gerber H, Essich G, Oulehla J, Lazary S. The genetic basis of equine allergic diseases. 1. Chronic hypersensitivity bronchitis.. Equine Vet J 1991 Nov;23(6):457-60.
                40. Gerber H. Sir Frederick Hobday memorial lecture. The genetic basis of some equine diseases.. Equine Vet J 1989 Jul;21(4):244-8.

                Citations

                This article has been cited 15 times.
                1. Simões J, Batista M, Tilley P. The Immune Mechanisms of Severe Equine Asthma-Current Understanding and What Is Missing.. Animals (Basel) 2022 Mar 16;12(6).
                  doi: 10.3390/ani12060744pubmed: 35327141google scholar: lookup
                2. Borowska A, Wolska D, Niedzwiedz A, Borowicz H, Jaworski Z, Siemieniuch M, Szwaczkowski T. Some Genetic and Environmental Effects on Equine Asthma in Polish Konik Horses.. Animals (Basel) 2021 Aug 3;11(8).
                  doi: 10.3390/ani11082285pubmed: 34438743google scholar: lookup
                3. Hulliger MF, Pacholewska A, Vargas A, Lavoie JP, Leeb T, Gerber V, Jagannathan V. An Integrative miRNA-mRNA Expression Analysis Reveals Striking Transcriptomic Similarities between Severe Equine Asthma and Specific Asthma Endotypes in Humans.. Genes (Basel) 2020 Sep 28;11(10).
                  doi: 10.3390/genes11101143pubmed: 32998415google scholar: lookup
                4. Couetil L, Cardwell JM, Leguillette R, Mazan M, Richard E, Bienzle D, Bullone M, Gerber V, Ivester K, Lavoie JP, Martin J, Moran G, Niedźwiedź A, Pusterla N, Swiderski C. Equine Asthma: Current Understanding and Future Directions.. Front Vet Sci 2020;7:450.
                  doi: 10.3389/fvets.2020.00450pubmed: 32903600google scholar: lookup
                5. Raudsepp T, Finno CJ, Bellone RR, Petersen JL. Ten years of the horse reference genome: insights into equine biology, domestication and population dynamics in the post-genome era.. Anim Genet 2019 Dec;50(6):569-597.
                  doi: 10.1111/age.12857pubmed: 31568563google scholar: lookup
                6. Tessier L, Côté O, Bienzle D. Sequence variant analysis of RNA sequences in severe equine asthma.. PeerJ 2018;6:e5759.
                  doi: 10.7717/peerj.5759pubmed: 30324028google scholar: lookup
                7. Mason VC, Schaefer RJ, McCue ME, Leeb T, Gerber V. eQTL discovery and their association with severe equine asthma in European Warmblood horses.. BMC Genomics 2018 Aug 2;19(1):581.
                  doi: 10.1186/s12864-018-4938-9pubmed: 30071827google scholar: lookup
                8. Pacholewska A, Kraft MF, Gerber V, Jagannathan V. Differential Expression of Serum MicroRNAs Supports CD4⁺ T Cell Differentiation into Th2/Th17 Cells in Severe Equine Asthma.. Genes (Basel) 2017 Dec 12;8(12).
                  doi: 10.3390/genes8120383pubmed: 29231896google scholar: lookup
                9. Lanz S, Brunner A, Graubner C, Marti E, Gerber V. Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity.. J Vet Intern Med 2017 Nov;31(6):1877-1883.
                  doi: 10.1111/jvim.14817pubmed: 28921663google scholar: lookup
                10. Tessier L, Côté O, Clark ME, Viel L, Diaz-Méndez A, Anders S, Bienzle D. Impaired response of the bronchial epithelium to inflammation characterizes severe equine asthma.. BMC Genomics 2017 Sep 8;18(1):708.
                  doi: 10.1186/s12864-017-4107-6pubmed: 28886691google scholar: lookup
                11. Pacholewska A, Marti E, Leeb T, Jagannathan V, Gerber V. LPS-induced modules of co-expressed genes in equine peripheral blood mononuclear cells.. BMC Genomics 2017 Jan 5;18(1):34.
                  doi: 10.1186/s12864-016-3390-ypubmed: 28056766google scholar: lookup
                12. Pacholewska A, Jagannathan V, Drögemüller M, Klukowska-Rötzler J, Lanz S, Hamza E, Dermitzakis ET, Marti E, Leeb T, Gerber V. Impaired Cell Cycle Regulation in a Natural Equine Model of Asthma.. PLoS One 2015;10(8):e0136103.
                  doi: 10.1371/journal.pone.0136103pubmed: 26292153google scholar: lookup
                13. Bosshard S, Gerber V. Evaluation of coughing and nasal discharge as early indicators for an increased risk to develop equine recurrent airway obstruction (RAO).. J Vet Intern Med 2014 Mar-Apr;28(2):618-23.
                  doi: 10.1111/jvim.12279pubmed: 24417562google scholar: lookup
                14. Racine J, Gerber V, Feutz MM, Riley CP, Adamec J, Swinburne JE, Couetil LL. Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using Ingenuity Pathway Analysis®.. BMC Vet Res 2011 Aug 15;7:48.
                  doi: 10.1186/1746-6148-7-48pubmed: 21843342google scholar: lookup
                15. Brosnahan MM, Brooks SA, Antczak DF. Equine clinical genomics: A clinician's primer.. Equine Vet J 2010 Oct;42(7):658-70.