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Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds

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Abstract

Linkage disequilibrium (LD) mapping is commonly used as a fine mapping tool in human genome mapping and has been used with some success for initial disease gene isolation in certain isolated inbred human populations. An understanding of the population history of domestic dog breeds suggests that LD mapping could be routinely utilized in this species for initial genome-wide scans. Such an approach offers significant advantages over traditional linkage analysis. Here, we demonstrate, using canine copper toxicosis in the Bedlington terrier as the model, that LD mapping could be reasonably expected to be a useful strategy in low-resolution, genome-wide scans in pure-bred dogs. Significant LD was demonstrated over distances up to 33.3 cM. It is very unlikely, for a number of reasons discussed, that this result could be extrapolated to the rest of the genome. It is, however, consistent with the expectation given the population structure of canine breeds and, in this breed at least, with the hypothesis that it may be possible to utilize LD in a genome-wide scan. In this study, LD mapping confirmed the location of the copper toxicosis in Bedlington terrier gene (CT-BT) and was able to do so in a population that was refractory to traditional linkage analysis.

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Acknowledgements

This study was supported by research grants from the Canine Control Council and John and Mary Kibble Trust. We are very appreciative of the cooperation and support of the members of the Bedlington Terrier Club of Queensland and of the veterinary practitioners providing case materials.

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Authors and Affiliations

  1. Companion Animal Sciences, School of Veterinary Science, University of Queensland, St Lucia, QLD 4072, Australia

    Changbaig Hyun & Lucio J. Filippich

  2. Immunogenetics Unit, School of Veterinary Science, University of Queensland, St Lucia, QLD 4072, Australia

    Ian P. Hughes

  3. Genomics Research Centre, School of Health Science, Griffith University, Gold Coast, QLD 4111, Australia

    Rod A. Lea, Graeme Shepherd & Lyn R. Griffiths

  4. Institute for Molecular Systematics, School of Biological Sciences, Victoria University of Wellington, New Zealand

    Rod A. Lea

  5. Victor Chang Cardiac Research Institute, Level 6, 384 Victoria Street, Darlinghurst, NSW, 2010, Australia

    Changbaig Hyun

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  1. Changbaig Hyun
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  2. Lucio J. Filippich
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  4. Graeme Shepherd
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Correspondence to Ian P. Hughes.

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http://linkage.rockefeller.edu/soft/gh/ , GENEHUNTER documentation.

http://www.iop.kcl.ac.uk/IoP/Departments/PsychMed/GEpiBSt/software.stm , King’s College, London, Institute of Psychiatry, Division of Psychological Medicine, Section of Epidemiology and Biostatistics.

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Hyun, C., Filippich, L.J., Lea, R.A. et al. Prospects for whole genome linkage disequilibrium mapping in domestic dog breeds . Mamm Genome 14, 640–649 (2003). https://doi.org/10.1007/s00335-003-3006-0

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