Have you had your Dachshund IVDD screened? If so, you can now help with an investigation into the genetics of IVDD

Investigating the genetics of disc calcification in Dachshunds

Background

Intervertebral disc disease (IVDD) is the most common cause of spinal injury in dogs and presenting clinical signs range from pain to complete and irreversible paralysis of the limbs. IVDD can affect all breeds but chondrodystrophic (short-legged) breeds are at highest risk and Dachshunds are more likely to be affected by IVDD than other breeds

In 2017 a genetic risk factor for IVDD was identified that segregates in multiple, short-legged breeds, including the Dachshund. This risk factor is known as the CDDY mutation, and dogs that carry this genetic variant are known to be at increased risk of IVDD compared to dogs that don’t carry it. 1-3

However, despite this shared genetic risk factor, individual dogs and breeds vary significantly with respect to their age and clinical presentation of IVDD, which suggests that additional genetic risk factors are involved, in addition to CDDY.

Reducing CDDY frequency clearly has the potential to lower IVDD incidence but for breeds where CDDY frequency is very high (fixed) this is not an option and, in these breeds, the successful reduction of IVDD incidence will be facilitated by the identification of as many additional risk factors as possible.

Disc calcification

There is also a relationship between IVDD and the presence of calcified intervertebral discs, and it is also known that disc calcification is inherited.4,5  This has led to the development of breeding programmes including radiographic screening for intervertebral disc calcification such as the UK Kennel Club scheme IVDD Scheme for Dachshunds | The Kennel Club.

The disc calcification score may be a more valuable tool with which to reduce IVDD incidence than CDDY testing, due to the presumed very high frequency of CDDY in the UK Dachshund population.6,7 And an even better approach might be to identify genetic risk factors for disc calcification, which would afford the opportunity of genetic screening for disc calcification risk, which could, ultimately, remove the need to undertake radiographic screening.

Aim:

This project, which is a collaboration between the University of Cambridge and Wisdom PanelÔ, will be a part of a PhD thesis investigating the genetics of intervertebral disc disease in dogs.

Specifically, we aim to investigate the underlying genetics of disc calcification in Dachshunds. For this, and with the help from our partners at Wisdom Panel, we will collect DNA from Dachshunds that have been assessed under The Kennel Club/ Dachshund Health UK IVDD Screening Programme and for which an official score is available.

We will genotype these dogs for genetic markers spread across the genome and identify regions of the genome that are associated with disc calcification score. As part of this investigation, we will genotype all these dogs for the CDDY mutation, enabling us to obtain the first accurate estimate of CDDY frequency in the UK Dachshund population.

If you own at least one Dachshund that has been screened under the Kennel Club/ Dachshund Health UK IVDD Screening Programme your dog(s) could help with this research.

How you can help:

-          If you agree to participate in this study, please visit The Canine Genetics Centre website to request your sample collection kit (https://www.canine-genetics.org.uk/research/sample-request-form/). Please request a kit for each dog that has been screened under the scheme.

-          We kindly ask the owners to fill out the “Sample Submission Form for Canine Genetic Research” that is included in the kit, including relevant history and/or veterinary reports.

-          The DNA collection procedure is painless and involves rolling a swab inside the dog’s mouth, between its cheek and gums for at least 10 seconds on each side of the mouth and for a total of 5 times. The swab should be moved across the entire cheek surface and avoiding the teeth.

-          The swabs will be allowed to air dry for at least 2 minutes, and then placed directly into the envelope and sealed with adequate identification.

-          The samples will be returned to The Canine Genetics Centre at the University of Cambridge.

-          The DNA will be extracted, and genotyping, using the Wisdom Panel, will be undertaken.

-          The genotyping data will be analysed, and a summary report will be shared between The Canine Genetics Centre, Wisdom PanelÔ and Dachshund Health UK, for this and future studies.

-          If regions of the genome are identified that are associated with disc calcification they will be assessed for their suitability for use as a genetic screening tool with which to reduce the incidence of IVDD in Dachshunds.

The PhD student

Bruno is an EBVSÒ Specialist in Veterinary Neurology, from Southfields Veterinary Specialists, who is also studying for a PhD on a part-time basis at Cambridge University Vet School under the supervision of neurologist Prof. Paul Freeman Dip ECVN and geneticist Dr. Cathryn Mellersh. Bruno, while based within The Canine Genetics Centre at the University of Cambridge, will be investigating the genetics of intervertebral disc diseases in dachshunds and other breeds of dog, with the aim being to improve our understanding of the genetics of this complex, debilitating disease that affects some of the UK’s most popular breeds.

Bruno is originally from Portugal and graduated from the ICBAS – University of Porto in 2013. He moved to the UK in June 2017 to work in a first opinion practice where he developed his interest in small animal neurology and completed the General Practitioner certificate in Neurology.  He has completed a Neurology internship and an ECVN-approved Residency in Neurology and Neurosurgery before moving to Southfields Veterinary Specialists to continue his Neurology journey.

References:

1. Batcher K et al. Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs. Genes (Basel), 2019. 10(6).

2. Brown EA et al. FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proc Natl Acad Sci U S A, 2017. 114(43): p. 11476-11481.

3. Bannasch D et al. The Effects of FGF4 Retrogenes on Canine Morphology. Genes (Basel), 2022. 13(2).

4. Lappalainen AK et al. Intervertebral disc disease in Dachshunds radiographically screened for intervertebral disc calcifications. Acta Vet Scand (2014) 56:89

5. Lappaleipen et al. Estimate of heritability and genetic trend of intervertebral disc calcification in Dachshunds in Finland. Acta Vet Scand (2015) 57:78

6. Bruun CS et al. Breeding schemes for intervertebral disc disease in dachshunds: Is disc calcification score preferable to genotyping of the FGF4retrogene insertion on CFA12? Canine Med Genet (2020) 7:18

7. Reunanen VLJ et al. Evaluation of intervertebral disc degeneration in young adult asymptomatic Dachshunds with magnetic resonance imaging and radiography. Acta Vet Scand (2023) 65:42