The work was done at the University of Missouri, Columbia, MO 65211.
A Truncated Retrotransposon Disrupts the GRM1 Coding Sequence in Coton de Tulear Dogs with Bandera's Neonatal Ataxia
Article first published online: 31 JAN 2011
Copyright © 2011 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 25, Issue 2, pages 267–272, March/April 2011
Total views since publication: 35
How to Cite
Zeng, R., Farias, F.H.G., Johnson, G.S., McKay, S.D., Schnabel, R.D., Decker, J.E., Taylor, J.F., Mann, C.S., Katz, M.L., Johnson, G.C., Coates, J.R. and O'Brien, D.P. (2011), A Truncated Retrotransposon Disrupts the GRM1 Coding Sequence in Coton de Tulear Dogs with Bandera's Neonatal Ataxia. Journal of Veterinary Internal Medicine, 25: 267–272. doi: 10.1111/j.1939-1676.2010.0666.x
- Issue published online: 7 MAR 2011
- Article first published online: 31 JAN 2011
- Submitted August 16, 2010; Revised October 29, 2010; Accepted November 19, 2010.
- Cerebellar ataxia;
- Genome-wide association study;
- Metabotropic glutamate receptor 1;
- Synaptic plasticity
Background: Bandera's neonatal ataxia (BNAt) is an autosomal recessive cerebellar ataxia that affects members of the Coton de Tulear dog breed.
Objective: To identify the mutation that causes BNAt.
Animals: The study involved DNA from 112 Cotons de Tulear (including 15 puppies with signs of BNAt) and 87 DNA samples from dogs of 12 other breeds.
Methods: The BNAt locus was mapped with a genome-wide association study (GWAS). The coding exons of positional candidate gene GRM1, which encodes metabotropic glutamate receptor 1, were polymerase chain reaction (PCR)-amplified and resequenced. A 3-primer PCR assay was used to genotype individual dogs for a truncated retrotransposon inserted into exon 8 of GRM1.
Results: The GWAS indicated that the BNAt locus was in a canine chromosome 1 region that contained candidate gene GRM1. Resequencing this gene from BNAt-affected puppies indicated that exon 8 was interrupted by the insertion of a 5′-truncated retrotransposon. All 15 BNAt-affected puppies were homozygous for the insert, whereas all other Cotons de Tulear were heterozygotes (n = 43) or homozygous (n = 54) for the ancestral allele. None of the 87 dogs from 12 other breeds had the insertion allele.
Conclusions and Clinical Importance: BNAt is caused by a retrotransposon inserted into exon 8 of GRM1. A DNA test for the GRM1 retrotransposon insert can be used for genetic counseling and to confirm the diagnosis of BNAt.