Dwarfism

***Before taking the steps to participate in any of our research projects, please read the article here.

Dwarfism

*** See here for details of taking radiographs

Lead contact: Lyons Lab – felinegenome@missouri.edu

Introduction

Dwarfism in cats has been recorded as early as the 1930s (1), but disappeared sometime during World War II. Dwarf cats were rediscovered in 1983 and established into a recognized breed, called Munchkin, in 1994 (2). To date, the Munchkin breed has not been fully clinically and genetically characterized.

In human achondroplasia, a mutation in the FGFR3 gene, is the most common form of dwarfism that occurs 1 in 15,000 live births (3). There are still many unknown causes of inherited dwarfism in people. Finding the gene responsible for bone development and growth, in Munchkin cats, may reveal a new function of a known gene and may suggest this gene to be implicated with dwarfism in other species.

Clinical Study

Other than the original publication, dwarfism has not been clinically examined in detail. We have initiated a project at MU to clinically define cat dwarfism in regards to the Munchkin breed and define any primary or secondary health concerns. For these studies, we are taking radiographs (X-rays) of the spine and the limbs of dwarf cats. We have also examined the vertebral spinal column using MRI. Our goal is to determine if Munchkin cats have other health concerns that are found in humans, such as heart disease, or found in dogs, such as intervertebral disc degenerations. We will be defining the extent of bone growth changes in the limbs of the Munchkins as well. The more cats we have – the more accurate our data.

Genetic Study

We are performing association and whole genome sequencing studies to identify the causal DNA variant for dwarfism in the Munchkin breed.

How can you help?

• We need radiographs of dwarf cats:

1. If you are near MU – we will perform the radiographs at no cost
2. Radiographs can be accepted from other veterinarians – please contact the Lyons laboratory to obtain details on the types of radiographs (X-rays) needed.

• For the genome-wide association study (GWAS) approach (DNA arrays):

1. We need buccal swab samples from dwarf cats, their normal parents and siblings. Buccal swab instructions and the submission form can be found here. Once we have found the gene and the DNA variant, DNA from the buccal swabs will be used to type additional cats to verify the accuracy of our discovery and to develop a genetic test.

• For potential whole genome sequencing (WGS):

1. We need 6 ml of EDTA whole blood from trios of cats – two parents and an offspring – where one individual is normal (long-legged – non-standard). Instructions for collection and shipping are found here.
2. Gonads can be submitted for DNA isolation as well. If you have a cat that is to be altered / desexed/ neutered or spayed – we can use these tissues for the projects as well (WGS or GWAS). See instructions here.
3. Tissues from a cat that you have recently had to euthanized or has passed can also be submitted. We are sorry for your loss – but maybe this kitty can contribute to science for other cats. Instructions for tissue submissions are here.

• Breeding information:

1. We are always interested in your experience with breeding to demonstrate the inheritance of dwarfism. Since dwarf cats have been found in different parts of the country, we need to consider more than one causal DNA variant. Please share your knowledge and expertise.

References:

1. William-Jones HE. (1944) Arrested Development of the Long Bones of the Fore-limbs in a Female Cat. Veterinary Record 46 (47) 449.
2. “Munchkin.” TICA Munchkin Breed Introduction. Web. 3 July 2014.
3. He L, Shobnam N, Wimley WC, Hristova KJ. (2011) FGFR3 Heterodimerization in Achondroplasia, the Most Common Form of Human Dwarfism, Biol. Chem., 286.

Funding:

This project was funded in part previously by the National Center for Research Resources R24 RR016094 and is currently supported by the Office of Research Infrastructure Programs OD R24OD010928, the Winn Feline Foundation and the Cat Health Network.