Research update from Dr. Casal on the project looking at what is commonly known as PES in our breed.
The objective of this study is to A) clinicopathologically and molecularly characterize microphthalmia with delayed growth in the Portuguese Water Dog (PWD) and B) develop a DNA-based test to assist breeders with their breeding programs and avoid producing affected dogs.
Objective A is over 95% complete. A draft of the paper describing the clinicopathological findings had been written but we found more data on affected puppies, which we are currently adding to the paper to be submitted by the end of May 2019. A paper was published about microphthalmia in PWDs recently by a group out of Cornell. However, this paper described only the ocular changes in affected dogs. With our publication, we will show that there are other abnormalities such as low platelet counts and stunted growth, which makes this a truly syndromic disorder. We have also included pedigree analyses showing the autosomal recessive mode of inheritance.
For Objective B, we received enough DNA samples from affected dogs and their relatives to perform an initial genome wide association study (GWAS). The DNA was aliquoted into plates for the GWAS and was sent to Illumina (Neogen) the end of November 2018. We received the results as expected in January 2019. We are absolutely thrilled with the results: A single, very significant peak was seen on the “Manhattan plot”, which allows us to locate not only the chromosome but the general area of that chromosome in which the gene must be located. Indeed, there is a gene in this area that, when mutated in mice and humans, causes a microphthalmia syndrome. We are currently in the process of sequencing this gene. If we do not find a disease-causing variant in this gene, we will sequence the entire genome of one affected dog and one normal PWD.