ABSTRACT
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.
Subject(s)
Cerebellar Ataxia/veterinary , Dog Diseases/genetics , Mutation , Receptors, Metabotropic Glutamate/genetics , Age of Onset , Animals , Cerebellar Ataxia/genetics , DNA Mutational Analysis/veterinary , DNA Primers/genetics , Dogs , Exons , Female , Genome-Wide Association Study , Genotype , Heterozygote , Homozygote , Male , Mutagenesis, Insertional , Open Reading Frames , Pedigree , RetroelementsABSTRACT
BACKGROUND: Driving under the influence of intoxicating drugs other than alcohol may be an important cause of traffic injuries. We used a rapid urine test to identify reckless drivers who were under the influence of cocaine or marijuana. METHODS: We conducted a consecutive-sample study in Memphis, Tennessee, in the summer of 1993. Subjects arrested for reckless driving who were not apparently impaired by alcohol (did not have an odor of alcohol, tested negative on breath analysis, or both) were tested for cocaine and marijuana at the scene of arrest. The results of the drug tests were compared with clinical evaluations of intoxication made at the scene by a police officer. RESULTS: A total of 175 subjects were stopped for reckless driving, and 150 (86 percent) submitted urine samples for drug testing at the scene of arrest. Eighty-eight of the 150 (59 percent) tested positive: 20 (13 percent) for cocaine, 50 (33 percent) for marijuana, and 18 (12 percent) for both drugs. Ninety-four of the 150 tested drivers were clinically considered to be intoxicated, and 80 of them (85 percent) tested positive for cocaine or marijuana. The intoxicated drivers had a broad range of affects and appearances. Nearly half the drivers intoxicated with cocaine performed normally on standard sobriety tests. CONCLUSIONS: Over half of the reckless drivers who were not intoxicated with alcohol were found to be intoxicated with other drugs. Toxicologic testing at the scene is a practical means of identifying drivers under the influence of drugs and is a useful adjunct to standard behavioral sobriety testing.
