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Genome-wide association studies for multiple diseases of the German Shepherd Dog

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Abstract

The German Shepherd Dog (GSD) is a popular working and companion breed for which over 50 hereditary diseases have been documented. Herein, SNP profiles for 197 GSDs were generated using the Affymetrix v2 canine SNP array for a genome-wide association study to identify loci associated with four diseases: pituitary dwarfism, degenerative myelopathy (DM), congenital megaesophagus (ME), and pancreatic acinar atrophy (PAA). A locus on Chr 9 is strongly associated with pituitary dwarfism and is proximal to a plausible candidate gene, LHX3. Results for DM confirm a major locus encompassing SOD1, in which an associated point mutation was previously identified, but do not suggest modifier loci. Several SNPs on Chr 12 are associated with ME and a 4.7 Mb haplotype block is present in affected dogs. Analysis of additional ME cases for a SNP within the haplotype provides further support for this association. Results for PAA indicate more complex genetic underpinnings. Several regions on multiple chromosomes reach genome-wide significance. However, no major locus is apparent and only two associated haplotype blocks, on Chrs 7 and 12 are observed. These data suggest that PAA may be governed by multiple loci with small effects, or it may be a heterogeneous disorder.

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Acknowledgments

We thank the American Kennel Club Canine Health Foundation for supporting this work and the Intramural Program of the National Human Genome Research Institute. We are grateful to the numerous dog owners and veterinarians who provided samples.

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Authors and Affiliations

  1. Department of Genetics and Biochemistry, College of Agriculture, Forestry and Life Sciences, Clemson University, Clemson, SC, 29634, USA

    Kate L. Tsai, Rooksana E. Noorai, Alison N. Starr-Moss, Caitlin J. Rinz, Keith E. Murphy & Leigh Anne Clark

  2. Cancer Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, 20892, USA

    Pascale Quignon & Elaine A. Ostrander

  3. Institut de Génétique et Développement de Rennes, CNRS-UMR6061, Université de Rennes 1, 2 avenue Prof. Léon Bernard, CS34317, Rennes Cedex, 35043, France

    Pascale Quignon

  4. Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX, 77843, USA

    Jörg M. Steiner

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  1. Kate L. Tsai
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  2. Rooksana E. Noorai
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Correspondence to Leigh Anne Clark.

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335_2011_9376_MOESM1_ESM.tif

Supplementary Fig. 1 Principal component analysis of 98 GSDs with PAA versus 79 healthy control GSDs. The x axis is principal component 1 and the y axis is principal component 2. Both populations appear to be evenly distributed throughout the cluster and no significant stratification was observed (TIFF 25530 kb)

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Tsai, K.L., Noorai, R.E., Starr-Moss, A.N. et al. Genome-wide association studies for multiple diseases of the German Shepherd Dog. Mamm Genome 23, 203–211 (2012). https://doi.org/10.1007/s00335-011-9376-9

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  • DOI: https://doi.org/10.1007/s00335-011-9376-9

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