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

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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.

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Acknowledgments

The Horse Trust, a UK horse charity committed to promoting education and welfare within the equine world, funded this project in the UK. In Switzerland, this study was supported by Vetsuisse and DKV grants, the Berne Equine Lung Research Group, and the Swiss National Science Foundation grant number 310000-116502. We thank Dr. Claire Wade of the Broad Institute for performing the BLAT search of known horse microsatellite sequences against the horse genome sequence, the information from which was used here to physically position the markers. Last but not least, we thank A. Ramseyer, U. Jost, N. Hasler, E. Laumen, P. Nussbaumer, and D. Burger and all horse owners for their help phenotyping the horses and collecting blood samples.

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Authors and Affiliations

  1. Animal Health Trust, Newmarket, Suffolk, CB8 7UU, UK

    June E. Swinburne, Helen Bogle & Elizabeth Temperton

  2. Centre for Preventive Medicine, Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk, CB8 7UU, UK

    June E. Swinburne

  3. Equine Clinic, Department of Veterinary Clinical Studies, Vetsuisse-Faculty, University of Berne, Langgass-strasse 124, 3012, Berne, Switzerland

    Jolanta Klukowska-Rötzler & Vincent Gerber

  4. Institute of Genetics, Vetsuisse-Faculty, University of Berne, Bremgartenstrasse 109A, 3001, Berne, Switzerland

    Jolanta Klukowska-Rötzler, Michaela Drögemüller, Tosso Leeb & Gaudenz Dolf

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  1. June E. Swinburne
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Correspondence to June E. Swinburne.

Electronic supplementary material

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335_2009_9214_MOESM1_ESM.xls

List of all of the markers used in the study and their relevant details Positions on the linkage map and on the genome sequence are given. A reference to the original publication is given, or, if unpublished, the NCBI accession number is given, or the primer sequences themselves(XLS 226 kb)

335_2009_9214_MOESM2_ESM.xls

Results of FASTLINK analysis of the two half-sibling families LOD scores greater than 1 are indicated in bold. LOD scores greater than 2 are indicated in grey(XLS 79 kb)

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Swinburne, J.E., Bogle, H., Klukowska-Rötzler, J. et al. A whole-genome scan for recurrent airway obstruction in Warmblood sport horses indicates two positional candidate regions. Mamm Genome 20, 504–515 (2009). https://doi.org/10.1007/s00335-009-9214-5

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  • DOI: https://doi.org/10.1007/s00335-009-9214-5

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