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Precision medicine and disease in cats

Mauler DA, Gandolfi B, Reinero CR, O’Brien DP. Spooner JL, Lyons LA, et al. Precision Medicine in Cats: Novel Niemann-Pick Type C1 diagnosed by whole-genome sequencing. J Vet Intern Med. 24 Feb 2017. DOI: 10.1111/jvim.14599 (Winn Funded)

In the world of the cat, available genetic and genomic resources are becoming more cost efficient and useful for health studies. The cost of whole genome sequencing can now be done for a similar cost to a magnetic resonance (MRI) scan.  While the turnaround time is not quite as quick as with humans, the availability of the DNA variant database developed by the 99 Lives Cat Genome Sequencing Initiative is a proven valuable first step for cats.

The variant database is comprised from a variety of cats of diverse populations and breeds, including those with and without known genetic health problems. Using the database supports identification of those DNA variants that cause health issues that might have a genetic component. This whole genome sequencing approach has already shown successes such as finding DNA variants associated with progressive retinal atrophy in Persians, the bobtail of the Japanese Bobtail breed and one variant responsible for a congenital myasthenic syndrome in Devon Rex and Sphynx-related cats.

The concept behind Precision Medicine is that clinicians will receive tools to better understand the complex mechanisms making up a cat’s health, disease, or condition, while being able to predict which treatments will be more effective or determine which polymorphisms lead to the need for different drug dosages. In the human, our individual genetic makeup is becoming an important part of our standard health care. It is felt to be the same for the cat using a Precision Medicine approach.

This paper demonstrates the use of whole genome sequencing for exactly this reason by describing a case of a 12-week old silver tabby intact female cat of probably American shorthair lineage that was presented for a new kitten examination. The kitten exhibited some abnormal physical findings including signs of a shaky, unsteady, hypermetric cat which caused the kitten to fall over. A presumptive diagnosis of cerebellar hypoplasia was made. Twelve weeks later, the kitten was referred to the Veterinary Health Center at the University of Missouri for concurrent liver and neurologic disease. The neurologic signs had progressed to where the kitten was unable to walk without support but still had good motor function and hypermetria in all four limbs. The neurologic signs were localized to the cerebellum. Because cats with cerebellar hypoplasia do not have progressive neurologic signs, a storage disorder was suspected instead. The cat continued to decline and was euthanized at an age of approximately 9 months.

Whole genome sequencing of the cat was performed using blood clots taken from prior samples collected. A mutation was found in the suspected NPC1 location which has been associated with Niemann-Pick C type disease. The NPC1 variant is considered rare since it was not identified in all the cats making up the 99 Lives sequence database.

It is important to note that over 40 genes with approximately 70 DNA variants have been documented to cause phenotypic, disease, or blood type variations in the domestic cat. The known DNA variants can be genotyped quickly and in a cost effective manner using panels appropriate for breeds, populations, or in cats as part of wellness care programs. The Precision Medicine approach can be utilized to resolve rare or undiagnosed cat cases.  (VT)

See also:
Montaque MJ, Li G, Gandolfi B, et al. Comparative analysis of the domestic cat genome reveals genetic signatures underlying feline biology and domestication. Pro Nat Acad Sci USA 2014: 111:17230-17235.