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Identification of the PLA2G6 c.1579G>A Missense Mutation in Papillon Dog Neuroaxonal Dystrophy Using Whole Exome Sequencing Analysis.
- Source :
-
PloS one [PLoS One] 2017 Jan 20; Vol. 12 (1), pp. e0169002. Date of Electronic Publication: 2017 Jan 20 (Print Publication: 2017). - Publication Year :
- 2017
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Abstract
- Whole exome sequencing (WES) has become a common tool for identifying genetic causes of human inherited disorders, and it has also recently been applied to canine genome research. We conducted WES analysis of neuroaxonal dystrophy (NAD), a neurodegenerative disease that sporadically occurs worldwide in Papillon dogs. The disease is considered an autosomal recessive monogenic disease, which is histopathologically characterized by severe axonal swelling, known as "spheroids," throughout the nervous system. By sequencing all eleven DNA samples from one NAD-affected Papillon dog and her parents, two unrelated NAD-affected Papillon dogs, and six unaffected control Papillon dogs, we identified 10 candidate mutations. Among them, three candidates were determined to be "deleterious" by in silico pathogenesis evaluation. By subsequent massive screening by TaqMan genotyping analysis, only the PLA2G6 c.1579G>A mutation had an association with the presence or absence of the disease, suggesting that it may be a causal mutation of canine NAD. As a human homologue of this gene is a causative gene for infantile neuroaxonal dystrophy, this canine phenotype may serve as a good animal model for human disease. The results of this study also indicate that WES analysis is a powerful tool for exploring canine hereditary diseases, especially in rare monogenic hereditary diseases.<br />Competing Interests: Although one of the authors (TI) is employed by a commercial company, (Thermo Fisher Scientific, Life Technologies Japan Ltd.), he has no competing interests concerning this work. This does not alter our adherence to PLOS ONE policies on sharing data and materials.
- Subjects :
- Amino Acid Sequence
Animals
Dogs
Female
Group VI Phospholipases A2 chemistry
Immunohistochemistry
Male
Neuroaxonal Dystrophies genetics
Pedigree
RNA, Messenger genetics
Reverse Transcriptase Polymerase Chain Reaction
Sequence Homology, Amino Acid
Dog Diseases genetics
Exome
Group VI Phospholipases A2 genetics
Mutation, Missense
Neuroaxonal Dystrophies veterinary
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 28107443
- Full Text :
- https://doi.org/10.1371/journal.pone.0169002