Hereditary eye diseases are one of the most common groups of diseases impairing the health of dogs. In the research for her doctoral dissertation, veterinarian Maria Kaukonen investigated the genetic background of three hereditary eye diseases that result in blindness by employing the latest research methods encompassing the entire genome. The research targets included microphthalmia in Irish Soft-Coated Wheaten Terriers, glaucoma in Norwegian Elkhounds and retinal degeneration in Miniature Schnauzers.
Based on Kaukonen’s results, three novel gene tests were developed to support dog breeding and diagnostics.
“Identifying gene defects underlying the disorders has made it possible to develop gene tests. Discovering the genetic cause also helps to better understand the disease process,” Kaukonen says.
New mode of maternal inheritance
Kaukonen investigated the genetic background of microphthalmia affecting the Wheaten Terriers, and identified a defect in the RBP4 gene as the cause of the disorder.
Normally, RBP4 transfers vitamin A from the mother to the puppy during gestation. Vitamin A is important for the normal development of several organs, and eyes are the most sensitive to its deficiency.
“The gene defect now located causes a vitamin A deficiency in developing puppies, which, in turn, leads to a disturbed eye development,” Kaukonen explains.
Simultaneously, a new mode of maternal inheritance was found, as the disease manifested only when the mother and the puppy were both homozygous for the variant. Normally in recessively inherited diseases the healthy parents are carriers of the associated gene defect, not homozygous for it.
“As far as we know, our study is the first to describe such a mode of maternal inheritance in any species. These results are very exciting, and in the future, the possibility of this kind of inheritance mode must be considered, especially when investigating developmental disorders,” notes Kaukonen.
Human patients benefit from the results too
Kaukonen also uncovered the genetic causes of open-angle glaucoma in Norwegian Elkhounds and retinal degeneration in Miniature Schnauzers. Millions of people suffer from these same diseases worldwide. In veterinary medicine, gene testing provides an efficient way of preventing new cases. In the case of humans, the accumulation of genetic knowledge makes it possible to develop gene therapies.
“When I was working on my dissertation, the first commercial pharmaceutical product based on gene therapy entered the market. In the future, the demand for similar drug products will undoubtedly be high, since gene therapy can be used to treat diseases for which there have been no treatments before,” Kaukonen reflects.
A canine DNA bank maintained by Professor Hannes Lohi’s research group currently holds specimens of over 70,000 pet dogs, of which roughly half have been analysed by veterinarians specialised in eye diseases.
“As a research resource, the dataset is truly extraordinary and also provides excellent opportunities for future gene discoveries,” Kaukonen sums up.
Kaukonen's doctoral dissertation is part of Professor Lohi’s project uncovering the genetic causes of canine hereditary diseases.
Public examination
Maria Kaukonen, DVM, will defend her doctoral dissertation entitled ‘Genetics of three canine eye disorders’ on 5 December 2019 at 12.00 at the Faculty of Veterinary Medicine, University of Helsinki. The public examination will take place at Porthania, the Suomen Laki hall, Yliopistonkatu 3. Professor Alison Hardcastle from University College London, United Kingdom, will serve as the opponent and Professor Hannes Lohi as the custos.