Version 1
: Received: 30 September 2024 / Approved: 1 October 2024 / Online: 1 October 2024 (04:58:55 CEST)
How to cite:
Zeng, R.; Guo, J.; Bullock, G.; Johnson, G. S.; Katz, M. L. Canine Multiple System Degeneration Associated with Sequence Variants in SERAC1. Preprints2024, 2024100014. https://doi.org/10.20944/preprints202410.0014.v1
Zeng, R.; Guo, J.; Bullock, G.; Johnson, G. S.; Katz, M. L. Canine Multiple System Degeneration Associated with Sequence Variants in SERAC1. Preprints 2024, 2024100014. https://doi.org/10.20944/preprints202410.0014.v1
Zeng, R.; Guo, J.; Bullock, G.; Johnson, G. S.; Katz, M. L. Canine Multiple System Degeneration Associated with Sequence Variants in SERAC1. Preprints2024, 2024100014. https://doi.org/10.20944/preprints202410.0014.v1
APA Style
Zeng, R., Guo, J., Bullock, G., Johnson, G. S., & Katz, M. L. (2024). Canine Multiple System Degeneration Associated with Sequence Variants in SERAC1. Preprints. https://doi.org/10.20944/preprints202410.0014.v1
Chicago/Turabian Style
Zeng, R., Gary S. Johnson and Martin L Katz. 2024 "Canine Multiple System Degeneration Associated with Sequence Variants in SERAC1" Preprints. https://doi.org/10.20944/preprints202410.0014.v1
Abstract
Canine Multiple System Degeneration (CMSD) is an early onset, progressive movement disorder affecting Kerry Blue Terriers and Chinese Crested dogs. The associated pathologic lesions include degeneration of the cerebellum, caudate nucleus and substantia nigra. CMSD is inherited as an autosomal recessive trait in both dog breeds. Previous linkage mapping localized the CMSD locus to a 15 MB region on canine chromosome 1 (CFA1). Next generation sequencing was used to generate whole genome sequences from DNA of an affected dog from each breed. The resulting sequence reads were aligned to the NCBI canine reference genome (build 3.1). Among the homozygous sequence variants within the CFA1 target region, a nonsense variant in exon 15 of SERAC1 was identified in the affected Kerry Blue Terrier, while in the Chinese Crested dog, a 4 bp deletion in the SERAC1 exon 4 acceptor splice site was found. RT-PCR showed that this deletion resulted in exon 4 skipping. Genotyping of large cohorts of Kerry Blue Terriers and Chinese Crested dogs for the respective breed-specific SERAC1 variants showed complete concordance between genotype and disease phenotype. Genotype-phenotype concordance was also observed in offspring generated by cross breeding between SERAC1-heterozygous Kerry Blue Terrier and Chinese Crested dogs, with only the compound heterozygotes exhibiting the disease phenotype, further confirming the recessive inheritance of CMSD. Variants in human SERAC1 are associated with disorders with a range of ages of disease onset and patterns of clinical signs, but that are all characterized by movement abnormalities similar to those of the dogs with CMSD. Canine CMSD could serve as a valuable model to elucidate the mechanisms underlying SERAC1-deficiency disorders and to evaluate potential therapeutic interventions.
Keywords
movement disorder; dog; mitochondria; whole genome sequencing; neurodegeneration
Subject
Biology and Life Sciences, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
