Leading the way: finding genes for neurologic disease in dogs using genome-wide mRNA sequencing
| العنوان: | Leading the way: finding genes for neurologic disease in dogs using genome-wide mRNA sequencing |
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| المؤلفون: | Elaine A. Ostrander, Holly C. Beale |
| المصدر: | BMC Genetics, Vol 13, Iss 1, p 56 (2012) BMC Genetics |
| بيانات النشر: | Springer Science and Business Media LLC, 2012. |
| سنة النشر: | 2012 |
| مصطلحات موضوعية: | SPTBN2 gene, Canines, lcsh:QH426-470, Cortical degeneration, Genomics, Disease, Biology, Genome, Frameshift mutation, Dogs, Genetics, medicine, Animals, Spinocerebellar Ataxias, Genetics(clinical), Dog Diseases, RNA, Messenger, Gene, Genotyping, Genetics (clinical), Neurodegenerative diseases, Spectrin, Sequence Analysis, DNA, RNAseq, medicine.disease, lcsh:Genetics, MRNA Sequencing, Mutation, Commentary, Spinocerebellar ataxia |
| الوصف: | Neonatal cerebellar cortical degeneration is a neurodegenerative disease described in several canine breeds including the Beagle. Affected Beagles are unable to ambulate normally from the onset of walking and the main pathological findings include Purkinje cell loss with swollen dendritic processes. Previous reports suggest an autosomal recessive mode of inheritance. The development of massively parallel sequencing techniques has presented the opportunity to investigate individual clinical cases using genome-wide sequencing approaches. We used genome-wide mRNA sequencing (mRNA-seq) of cerebellum tissue from a single Beagle with neonatal cerebellar cortical degeneration as a method of candidate gene sequencing, with the aim of identifying the causal mutation.A four-week old Beagle dog presented with progressive signs of cerebellar ataxia and the owner elected euthanasia. Histopathology revealed findings consistent with cerebellar cortical degeneration. Genome-wide mRNA sequencing (mRNA-seq) of RNA from cerebellum tissue was used as a method of candidate gene sequencing. After analysis of the canine orthologues of human spinocerebellar ataxia associated genes, we identified a homozygous 8 bp deletion in the β-III spectrin gene, SPTBN2, associated with spinocerebellar type 5 in humans. Genotype analysis of the sire, dam, ten clinically unaffected siblings, and an affected sibling from a previous litter, showed the mutation to fully segregate with the disorder. Previous studies have shown that β-III spectrin is critical for Purkinje cell development, and the absence of this protein can lead to cell damage through excitotoxicity, consistent with the observed Purkinje cell loss, degeneration of dendritic processes and associated neurological dysfunction in this Beagle.An 8 bp deletion in the SPTBN2 gene encoding β-III spectrin is associated with neonatal cerebellar cortical degeneration in Beagle dogs. This study shows that mRNA-seq is a feasible method of screening candidate genes for mutations associated with rare diseases when a suitable tissue resource is available. |
| تدمد: | 1471-2156 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::816cfe0dddd6439d153fd2add9164dd2Test https://doi.org/10.1186/1471-2156-13-56Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....816cfe0dddd6439d153fd2add9164dd2 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14712156 |
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