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Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q

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Abstract

Selective malabsorption of cobalamin (vitamin B12) accompanied by proteinuria, known as Imerslund-Gräsbeck syndrome or megaloblastic anemia 1 (I-GS, MGA1; OMIM 261100), is a rare autosomal recessive disorder. In Finnish kindreds, I-GS is caused by mutations in the cubilin gene (CUBN), located on human Chromosome (Chr) 10. However, not all patients have CUBN mutations, and three distinct mutations in the amnionless gene, AMN, were very recently identified in patients from Norwegian and Israeli families. The present study demonstrates that in a large canine I-GS pedigree, the disease is genetically linked (peak multipoint LOD score 11.74) to a region on dog Chr 8 that exhibits conserved synteny with human Chr 14q. Multipoint analysis indicates that the canine disease gene lies in an interval between the echinoderm microtubule-associated, protein-like 1 (EML1) gene and the telomere. A single critical recombinant further suggests that the disease gene is between markers in EML1 and the G protein-coupled receptor (G2A) gene, defining an I-GS interval in the human genome that contains the AMN gene. Thus, these comparative-mapping data provide evidence that canine I-GS is a homologue of one form of the human disease and will provide a useful system for understanding the molecular mechanisms underlying the disease in humans.

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Acknowledgements

We thank Shana Gilbert-Gregory for excellent technical assistance. This work was supported by National Institutes of Health Grants DK45341, DK064161, and RR02512, the Companion Animal Fund of the MSU College of Veterinary Medicine, and by funds from the Dean’s Office, School of Veterinary Medicine, University of Pennsylvania.

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Authors and Affiliations

  1. Laboratory of Comparative Medical Genetics, College of Veterinary Medicine, Michigan State University, East Lansing, Michigan 48824, USA

    Qianchuan He, John C. Fyfe & Adam Kilkenney

  2. National Center for Biotechnology Information, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20894, USA

    Alejandro A. Schäffer

  3. Section of Medical Genetics, University of Pennsylvania School of Veterinary Medicine, 3900 Delancey St., Philadelphia, Pennsylvania 19104-6010, USA

    Petra Werner & Paula S. Henthorn

  4. The Institute for Genomic Research, Rockville, Maryland 20850, USA

    Ewen F. Kirkness

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  1. Qianchuan He
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He, Q., Fyfe, J.C., Schäffer, A.A. et al. Canine Imerslund-Gräsbeck syndrome maps to a region orthologous to HSA14q . Mamm Genome 14, 758–764 (2003). https://doi.org/10.1007/s00335-003-2280-1

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  • DOI: https://doi.org/10.1007/s00335-003-2280-1

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