Golden Retriever dogs with neuronal ceroid lipofuscinosis have a two-base-pair deletion and frameshift in CLN5
| Autor: | D. Gilliam, Martin L. Katz, Gary S. Johnson, Jeremy F. Taylor, Robert D. Schnabel, A. Kolicheski, Tendai Mhlanga-Mutangadura |
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| Rok vydání: | 2015 |
| Předmět: |
Ataxia
Base pair Endocrinology Diabetes and Metabolism Golden Retriever Biology medicine.disease_cause Biochemistry Frameshift mutation Dogs Endocrinology Neuronal Ceroid-Lipofuscinoses Genetics medicine Animals Dog Diseases Allele Frameshift Mutation Molecular Biology Sequence Deletion Mutation Base Sequence Homozygote Membrane Proteins Heterozygote advantage Sequence Analysis DNA medicine.disease Neuronal ceroid lipofuscinosis medicine.symptom |
| Zdroj: | Molecular Genetics and Metabolism. 115:101-109 |
| ISSN: | 1096-7192 |
| DOI: | 10.1016/j.ymgme.2015.04.001 |
| Popis: | We studied a recessive, progressive neurodegenerative disease occurring in Golden Retriever siblings with an onset of signs at 15 months of age. As the disease progressed these signs included ataxia, anxiety, pacing and circling, tremors, aggression, visual impairment and localized and generalized seizures. A whole genome sequence, generated with DNA from one affected dog, contained a plausibly causal homozygous mutation: CLN5:c.934_935delAG. This mutation was predicted to produce a frameshift and premature termination codon and encode a protein variant, CLN5:p.E312Vfs*6, which would lack 39 C-terminal amino acids. Eighteen DNA samples from the Golden Retriever family members were genotyped at CLN5:c.934_935delAG. Three clinically affected dogs were homozygous for the deletion allele; whereas, the clinically normal family members were either heterozygotes (n = 11) or homozygous for the reference allele (n = 4). Among archived Golden Retrievers DNA samples with incomplete clinical records that were also genotyped at the CLN5:c.934_935delAG variant, 1053 of 1062 were homozygous for the reference allele, 8 were heterozygotes and one was a deletion-allele homozygote. When contacted, the owner of this homozygote indicated that their dog had been euthanized because of a neurologic disease that progressed similarly to that of the affected Golden Retriever siblings. We have collected and stored semen from a heterozygous Golden Retriever, thereby preserving an opportunity for us or others to establish a colony of CLN5-deficient dogs. |
| Databáze: | OpenAIRE |
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