Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog

dc.contributor.author Mansour, Tamer
dc.contributor.author Sebbag, Lionel
dc.contributor.author Woolard, Kevin
dc.contributor.author Vernau, Karen
dc.contributor.author Ancona, Devin
dc.contributor.author Thomasy, Sara
dc.contributor.author Sebbag, Lionel
dc.contributor.author Moore, Bret
dc.contributor.author Knipe, Marguerite
dc.contributor.author Seada, Haitham
dc.contributor.author Cowan, Tina
dc.contributor.author Aguilar, Miriam
dc.contributor.author Brown, C. Titus
dc.contributor.author Bannasch, Danika
dc.contributor.department Biomedical Sciences
dc.contributor.department Veterinary Clinical Sciences
dc.date 2020-04-20T22:26:20.000
dc.date.accessioned 2020-07-07T05:12:27Z
dc.date.available 2020-07-07T05:12:27Z
dc.date.copyright Wed Jan 01 00:00:00 UTC 2020
dc.date.issued 2020-04-16
dc.description.abstract <p>Mucopolysaccharidosis (MPS) is a metabolic storage disorder caused by the deficiency of any lysosomal enzyme required for the breakdown of glycosaminoglycans. A 15-month-old Boston Terrier presented with clinical signs consistent with lysosomal storage disease including corneal opacities, multifocal central nervous system disease and progressively worsening clinical course. Diagnosis was confirmed at necropsy based on histopathologic evaluation of multiple organs demonstrating accumulation of mucopolysaccharides. Whole genome sequencing was used to uncover a frame-shift insertion affecting the alpha-L-iduronidase (IDUA) gene (c.19_20insCGGCCCCC), a mutation confirmed in another Boston Terrier presented 2 years later with a similar clinical picture. Both dogs were homozygous for the IDUA mutation and shared coat colors not recognized as normal for the breed by the American Kennel Club. In contrast, the mutation was not detected in 120 unrelated Boston Terriers as well as 202 dogs from other breeds. Recent inbreeding to select for recessive and unusual coat colors may have concentrated this relatively rare allele in the breed. The identification of the variant enables ante-mortem diagnosis of similar cases and selective breeding to avoid the spread of this disease in the breed. Boston Terriers carrying this variant represent a promising model for MPS I with neurological abnormalities in humans.</p>
dc.description.comments <p>This article is published as Mansour, Tamer A., Kevin D. Woolard, Karen L. Vernau, Devin M. Ancona, Sara M. Thomasy, Lionel Sebbag, Bret A. Moore et al. "Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog." <em>Scientific Reports</em> 10 (2020): 6558. DOI: <a href="https://doi.org/10.1038/s41598-020-63451-4" target="_blank">10.1038/s41598-020-63451-4</a>. Posted with permission.</p>
dc.format.mimetype application/pdf
dc.identifier archive/lib.dr.iastate.edu/vcs_pubs/43/
dc.identifier.articleid 1042
dc.identifier.contextkey 17468262
dc.identifier.s3bucket isulib-bepress-aws-west
dc.identifier.submissionpath vcs_pubs/43
dc.identifier.uri https://dr.lib.iastate.edu/handle/20.500.12876/91923
dc.language.iso en
dc.source.bitstream archive/lib.dr.iastate.edu/vcs_pubs/43/2020_SebbagLionel_WholeGenome.pdf|||Sat Jan 15 00:15:23 UTC 2022
dc.source.uri 10.1038/s41598-020-63451-4
dc.subject.disciplines Animal Diseases
dc.subject.disciplines Congenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subject.disciplines Genomics
dc.subject.disciplines Small or Companion Animal Medicine
dc.subject.disciplines Veterinary Pathology and Pathobiology
dc.subject.keywords Animal breeding
dc.subject.keywords Disease genetics
dc.subject.keywords Experimental models of disease
dc.subject.keywords Genetic testing
dc.subject.keywords Genetics research
dc.subject.keywords Metabolic disorders
dc.subject.keywords Neurological disorders
dc.subject.keywords Next-generation sequencing
dc.title Whole genome sequencing for mutation discovery in a single case of lysosomal storage disease (MPS type 1) in the dog
dc.type article
dc.type.genre article
dspace.entity.type Publication
relation.isAuthorOfPublication 3f7ce870-c6d0-4420-8cde-95e5d6290597
relation.isOrgUnitOfPublication 184db3f2-d93f-4571-8ad7-07c8a9e6a5c9
relation.isOrgUnitOfPublication 1ad68def-86ae-460b-8808-f1b1febafd0a
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