1. Precision Medicine in Cats: Novel Niemann‐Pick Type C1 Diagnosed by Whole‐Genome Sequencing
- Author
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Mauler, D.A., Gandolfi, B., Reinero, C.R., O'Brien, D.P., Spooner, J.L., Lyons, L.A., Aberdein, Danielle, Alves, Paulo C., Barsh, Gregory S., Beale, Holly C., Boyko, Adam R., Brockman, Jeffrey A., Castelhano, Marta G., Chan, Patricia P., Matthew Ellinwood, N., Fogle, Jonathan E., Garrick, Dorian J., Helps, Christopher R., Hytönen, Marjo K., Kaukonen, Maria, Kaelin, Christopher B., Leclerc, Emilie, Leeb, Tosso, Lohi, Hannes, Longeri, Maria, Malik, Richard, Montague, Michael J., Munday, John S., Murphy, William J., Pedersen, Niels C., Rothschild, Max F., Stern, Joshua A., Swanson, William F., Terio, Karen A., Todhunter, Rory J., Ueda, Yu, Warren, Wesley C., Wilcox, Elizabeth A., Wildschutte, Julia H., Medicum, Research Programme for Molecular Neurology, Hannes Tapani Lohi / Principal Investigator, Veterinary Genetics, Veterinary Biosciences, and Research Programs Unit
- Subjects
0301 basic medicine ,Pathology ,medicine.medical_specialty ,Felis silvestris catus ,SIAMESE CATS ,Population ,Case Report ,Genomics ,Case Reports ,Biology ,PHENOTYPE ,413 Veterinary science ,medicine.disease_cause ,DNA sequencing ,Feline ,Lysosomal storage ,03 medical and health sciences ,LIPIDOSIS ,0302 clinical medicine ,medicine ,Missense mutation ,education ,Gene ,Genetics ,Whole genome sequencing ,education.field_of_study ,Mutation ,CATS ,IDENTIFICATION ,General Veterinary ,MUTATIONS ,ABNORMALITIES ,NPC1 ,3. Good health ,MODEL ,030104 developmental biology ,Neurology ,2-HYDROXYPROPYL-BETA-CYCLODEXTRIN ,SMALL ANIMAL ,DISEASE TYPE-C ,SYSTEM ,WGS ,030217 neurology & neurosurgery - Abstract
H. Lohi on työryhmä 99 Lives Consortium jäsen. State-of-the-art health care includes genome sequencing of the patient to identify genetic variants that contribute to either the cause of their malady or variants that can be targeted to improve treatment. The goal was to introduce state-of-the-art health care to cats using genomics and a precision medicine approach. To test the feasibility of a precision medicine approach in domestic cats, a single cat that presented to the University of Missouri, Veterinary Health Center with an undiagnosed neurologic disease was whole-genome sequenced. The DNA variants from the cat were compared to the DNA variant database produced by the 99 Lives Cat Genome Sequencing Consortium. Approximately 259 genomic coverage was produced for the cat. A predicted p.H441P missense mutation was identified in NPC1, the gene causing Niemann-Pick type C1 on cat chromosome D3.47456793 caused by an adenine-to-cytosine transversion, c.1322A>C. The cat was homozygous for the variant. The variant was not identified in any other 73 domestic and 9 wild felids in the sequence database or 190 additionally genotyped cats of various breeds. The successful effort suggested precision medicine is feasible for cats and other undiagnosed cats may benefit from a genomic analysis approach. The 99 Lives DNA variant database was sufficient but would benefit from additional cat sequences. Other cats with the mutation may be identified and could be introduced as a new biomedical model for NPC1. A genetic test could eliminate the disease variant from the population.
- Published
- 2017
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