American Spaniel Club Foundation
The ASCF is a non-profit corporation with the general purpose to “engage in, advance, promote and administer charitable, scientific and educational activities and projects” on behalf of flushing spaniels and in particular cocker spaniels.
ASCF was founded to provide an opportunity for individuals to make tax deductible contributions, an opportunity for corporations whose charitable giving programs call for education and research efforts to make tax deductible gifts, an opportunity for corporations to match donations through their matching gift programs, and most importantly, to support the efforts of ASC to raise funds to support educational programs, rescue and research for the welfare and betterment of the flushing spaniels that have give us so much love and joy.
For more information or to donate to ASCF, please visit the American Spaniel Club Foundation Website
MOLECULAR GENETIC STUDIES OF INHERITED CATARACTS IN THE AMERICAN COCKER SPANIEL
Attention: Below is a summary by ASC FOUNDATION Scientific Research Chair Doug McFarlane of the Mid-Year Progress Report from Dr. Aguirre at University of Pennsylvania
· Purpose: This report was pulled together two months AFTER the June 2018 podcast with Dr. Aguirre so it contains additional progress information which Doug has distilled. If you want, you can also read the full 13 page PDF of the report found under FILES on the ASC Yahoo Group page. To revisit the podcast – click here: https://fccdl.in/7tjHSukqVp
· Eye Exams Need to Continue: While significant progress has been made in recent months, they still need YOU and YOUR COCKERS – any and all with pedigrees. At this point, Cockers ALREADY INCLUDED in the study are the most important because the true key for the assessment of a phenotype is the observation of the progression – or lack of – over time. So be sure to bring in your already-included Cockers for re-checks and have your eye vet complete the research paper linked below. http://www.optigen.com/doc/Cocker_Spaniel_Inherited_Cataract_Research_form2_27_17.pdf
· The need for funding is never ending. While DNA contributions and eye exams are finally strong enough, financial contributions have slowed and we need to make up the difference. You will be hearing from the Eye Support Cockers fund raising team shortly but no time like the present to consider a memorial donation for a lost loved one, family member, friend or fur baby. A wonderful way to support their legacy and the future of our breed. Checks made out to ASC Foundation are tax deductible too.
On behalf of the ASC Foundation Board of Directors, thank you for your continued support and interest in this important research. Please feel free to share this information on social media, etc. // Charles Born, ASCF Communications Chair.
Summary by ASC FOUNDATION Scientific Research Chair Doug McFarlane of the Mid-Year Progress Report from Dr. Aguirre at University Of Pennsylvania
The Project continues to focus on the identification of the genes and genetic variations responsible for inherited cataracts in American Cocker Spaniels (ACS). The goal is to develop a genetic test that can identify genetically normal, affected and carrier dogs. ACS dogs with inherited cataracts are born with normal lenses, which then proceed to opacify over time, leading to blindness by 2-10 years of age.
The mechanism of inheritance in ACS has been previously proposed as being autosomal recessive, but our recent observations suggests a more complex than one predicted. We have been able to advance our analysis by updating cases and control samples by working with breeders/owners which has become a critical step in our work. The need to keep the database updated has allowed us to pinpoint specific areas of the genome associated in various ways with the condition.
With the enhanced gathering of information about each sample we were able to select candidate cases for cataracts predictable as having a genetic cause. Specifically, inherited cataracts in ACS are thought to appear sometime around 2-5 years of age and progress. Although now we have found a subset of cases where cataracts presumably inherited begin between 5-9 years of age.
Research going forward will be based on three main principles which are described in more detail in the full report. These principles are (1) Construction of a suitable dataset obtained through the identification of cases (2) mapping of the mutation(s) and (3) validation through sequencing. The ideal result in the study using these principles involves mapping the disease to a specific chromosomal region and sequencing a presumed candidate gene for the validation of the data once the genomic region is identified.
PROGRESS TO DATE
Candidate Genes: As previously reported the selection of candidate genes based on prior data about the same or similar diseases in other dogs and species proved to be negative. There was no association with the cataract physical characteristics. This was more thoroughly discussed in previous progress reports.
Pedigree Analysis: In the previous report we described the analysis of pedigrees to determine a probable mode of inheritance. The work showed no mode of inheritance based on pedigrees alone. However, we were able to link most of our affected subjects to three common ancestors. Therefore, we hypothesized that an autosomal recessive inheritance is at play, and that such a model would explain a significant part of our cases. A deeper analysis of the that then suggested that a common, shared mutation causing ALL the genetic cataracts in ACS is unlikely.
Samples Received: A significant part of the progress we are making is the increased number of dogs participating to 750 from the 675 previous number. This is a significant increase and is most welcome.
Phenotype Reassessment: With the aid of more samples and the use the standardized Exam Forms we discovered two distinct Phenotypes (physical characteristics) of inherited cataracts. (1) the possibility of separating in regard to age and onset, and (2) we noted the emergence of a second phenotype, where one eye develops a cataract at an early age and several years later a second cataract appears in the other eye.
Genotyping and Data Analysis: Since our last report, and because of the work carried out in the phenotype reassessment, we were able to increase the suitable sample size for the research to 136 dogs. Dogs were divided into 63 cases and 73 controls. Each cases and controls was further classified by age of onset, type and location of the cataract and reliability of the sample. With this expanded and better set of data further analysis was done. Again, the aim of this phase of the work was to associate a specific genomic region and its markers to a group of study cases.
Various statistical study techniques were again conducted with this improved data set. The results indicated that roughly 80% of all samples would fall within one of the two sub-populations. Further analysis was done on each of these two populations searching for a specific region in the chromosome where the indications were the strongest. Two specific areas on the chromosome were statistically significant showing a higher indication for the affected area.
Additional analysis continues on these two sub-populations. If these regions detected through this upcoming analysis shows variants causative for cataracts, or at least increasing the dog’s vulnerability to the development of one, this may confirm our hypothesis that not all cases can be explained as inherited from a single parent. The specific strategy going forward is then with more certainty to look for a complex disease which is consistent with our previous report that the occurrence of cataracts in ACS is a probable complex of diseases.
Even though we cannot currently show a simple and complete association of a single marker with the ACS cataract, we have found we can trace and identify trends and associations both under the assumption of a recessive disease, and under the assumption of a disease associated with an area of vulnerability on the chromosome not necessarily inherited in a recessive manner. This might imply the co-existence of multiple factors, not necessarily all of them genetic.
Our work continues as we continue to expand the set of data by working with breeders/owners to gather new and confirm existing data. This is extremely important as we have shown that as the quality of data improves so then does the opportunity to discover and confirm results.
The full report is available, and it describes these results in more detail. I have attempted to summarize 13 pages of a more technical discussion into 3 pages with less technical explanations. I sincerely hope I have properly conveyed the positive research progress that has occurred.
ASCF Scientific Research Chair