SCWTCA ENDOWMENT, INC. – SUPPORTING WHEATEN HEALTH, RESEARCH AND EDUCATION


2001 SCWTCA Endowment established.
The Endowment had its origins in the 1995 establishment of the SCWTCA Health Fund. By 2001, the decision was made to create a separate non-profit which was incorporated in 2004 as the SCWTCA Endowment, Inc. The Endowment gained 501(c)3 status effective in 2004.
Ongoing Fecal A1PI Kit Program:
Distribution points set throughout the US & Canada.
2002 Vaden Grant - AKC CHF Grant 2219:
Longitudinal Clinical Study, Mode of Inheritance and Therapeutic Trials for PLE/PLN in Soft Coated Wheaten Terriers. Shelly Vaden DVM PhD DACVIM, NCSU. $55,600 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.
2003, 2004 Colony Dog Adopt a Colony Dog Fundraiser established.
Coordinated fundraising campaign to individual sponsors and regional clubs for each colony dog living at NCSU. Approved by SCWTCA, Inc. Funded by SCWTCA Endowment Colony Dog. Expenses incurred by SCWTCA Endowment $13,300.
2006 AKC/CHF:
Genetic Determinants of Malignant Melanoma (Michael Kent DVM, UC Davis); $1,000 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.
2006 Investigation of Antigenic Causes of Vaccine-Associated Allergic Reactions in Dogs:
Dr. George Moore, Purdue University.
2006 4th Annual CHF Canine Health Conference - Chicago, IL:
Attendees Elaine Azerolo and Susan McGee. $5,000 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.
2007 & 2008 University of Missouri Canine Phenome Project:
2007 – The purpose of the Canine Phenome Project is to establish a DNA bank with supporting data for use by researchers to identify the genes responsible for canine diseases and other characteristics. Includes Siblings Pair Study – Gary Johnson DVM Ph.D. Approved by SCWTCA, Inc. Funded by SCWTCA Endowment; $35,200 includes blood draw clinics and SNIP.
2008 Rabies Challenge Charity Trust:
$500 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment
2008 AKC CHF Conference:
Jana Carraway. $200 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.
2008 Lifetime Health Survey:
National Institute of Health, Ostrander Canine Genomics Lab Canine Phenome Project.
2012 Informative Family Project, Geriatric Dog Project contributing to AKC-CHF Grant 1485 Study of PLE/PLN (Protein-Losing Enteropathy/Nephropathy) in Soft-Coated Wheaten Terriers:
University of PA, Meryl Littman, VMD, DACVIM. $9,000

Pelletizing DNA for Penn DNA Bank. Biopsies, shipping of samples, summer students, genetic testing DNA collection kits, AKC report fees for Penn on registration numbers, histopathology, testing expense and freezer expense. Summer students also helped with the Open Registry, with the collection of DNA samples, and acquiring medical records for phenotypic information for dogs with PLE/PLN, IBD, Addison’s disease, and renal dysplasia.

After years of research supported by hundreds of Wheatens and their owners and breeders, Meryl Littman VMD DACVIM and Paula Henthorn PhD at the University of Pennsylvania School of Veterinary Medicine (Penn Vet) identified mutations associated with PLN in two genes. A simple cheek swab test to determine an individual dog’s DNA status was introduced to Wheaten owners in May 2012. $38,800 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.

2012 Student Researcher Professional Development Award:
Claire Wiley – Grant. $560 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.
2012 Genome-Wide Association Study (GWAS) of Protein-Losing Nephropathy (PLN) in Soft Coated Wheaten Terriers, Genetic Testing for PLN-Associated Variant Genes:
University of PA, Meryl Littman VMD DACVIM, Paula Henthorn PhD BS, Claire Wiley. University of PA offers a DNA test for PLN Associated Variant Alleles. By May of 2012, we had distributed 2,750 DNA test kits in support of DNA testing for PLN-associated variant alleles at University of PA. By early September 2012, Dr. Littman advised us that they had received approximately 1,000 samples with the help of the Endowment, GRF, and SCWTCA, Inc.
2013 TUFTS University Breeding & Genetics Conference:
Attendee Deb Van De Ven. $235 Approved by SCWTCA, Inc. Funded by SCWTCA Endowment.
2013 Purchase of Database and Maintenance:
After a number of years of development, the SCWTCA Endowment, Inc. is excited to announce the launch the Soft Coated Wheaten Terrier Database at http://www.scwtdb.org. $7,600
2014 Trustees of the University of Pennsylvania School of Veterinary Medicine SCWT Histopathology & Testing Expense
$5,000
2015 Freezer Storage:
University of Pennsylvania, School of Veterinary Medicine Trustees of the Univ. of PA School of Veterinary Medicine (Purchase of a new freezer to store SCWT DNA samples $9,142)
2016 University of Pennsylvania, Protein Losing Enteropathy (PLE) Research:
$9,000 Pilot association study of PLE/PLN in SCWTs. Paula Henthorn PhD BS and Meryl Littman VMD DACVIM. Nearly one hundred DNA samples have been chosen for initial analysis in the Section of Medical Genetics at the University of PA School of Veterinary Medicine.
2018 AKC CHF Grant 2519: Prevalence of Bartonella spp. Infection in Dogs with Cardiac and Splenic Hemangiosarcomas within and between Geographic Locations:
Edward B Breitschwerdt DVM; Matthew Breen PhD; North Carolina State University. $2,500 Funded by the SCWTCA Endowment.
2019 Genome-Wide Association Studies (GWAS) using SNP chips for Protein Losing Enteropathy (PLE):
University of Pennsylvania School of Veterinary Medicine, Paula Henthorn PhD BS $7,750
2019 Genetic Testing for PLN-Associated Variant Genes Follow Up Survey:
University of Pennsylvania School of Veterinary Medicine, Paula Henthorn, PhD BS, Mariah Gentry DVM.$5,000
2019 Whole Genome Sequencing (WGS), University of Pennsylvania
Researcher: Paula Henthorn. Since the introduction of the DNA test for PLN risk, owners and breeders have continued to hope for some similar testing for PLE. As noted, it is a more complex disease. WGS is an important component of this research.

WGS identifies essentially ALL of the DNA variants in an individual (there are millions of DNA variants within an individual mammal, compared to another member of the same species). The overall goal of WGS (combined with other information) is to identify all of the DNA variants in healthy and disease affected dogs, then to find which of those variants are associated with disease. This is done by analyzing the genome sequences by comparing to sequences of other dogs, examining genes known to be involved with the particular or similar diseases, such as inflammatory bowel diseases for PLE, and by performing GWAS (Genome Wide Association Studies with SNP chips) to point to the chromosomal regions that need to be studied. The goal of the proposed studies, combined together, is to further improve our ability to predict the occurrence of PLN. Dr. Henthorn has submitted 10 dogs for WGS sequencing to advance to our understanding of both PLE and PLN.

This sequencing information will make a significant contribution to our PLE research. Additional sequencing would build on that information, and it is particularly important to obtain sequence from PLE and normal geriatric dogs from the U.S. population. If we are very lucky, the WGS studies will immediately identify genes for further study. More likely, as implied above, we will need to do additional GWAS (genome-wide association studies) in the future.

In particular, Dr. Henthorn will compare genome sequences from affected and healthy geriatric dogs that are 2-2 (”2s” in the SCWT vernacular) to see if we can identify DNA changes that would allow us to more accurately predict the occurrence of PLN. An added benefit of the sequencing could find a dog(s) who have a variance for both PLE and PLN.

Penn Vet is collaborating with investigators at the Children’s Hospital of Philadelphia (CHOP), who study a form of IBD in very young children that appears similar to PLE in some SCWTs. If they find that the dogs have a similar genetic basis to their disease as do children, it opens the possibility of exciting collaborative work that could be mutually beneficial to dogs and kids.

We also want to sequence dogs affected with PLN and compare their genome sequences to healthy geriatric dogs (which will include the PLN 2-2 healthy geriatric dogs).

2020 PLN Gene Testing – 2 vs 1
Testing for variant alleles associated with a risk for PLN ("DNA test) was initially developed at Penn based on Drs. Littman and Henthorn's research. That research showed that a DNA variant occurred in each of two genes, NPHS1 and KIRREL2, that are next to each other in their position on dog chromosome 1, and that the presence of these two variants on both copies of chromosome 1 indicated significantly increased risk for developing PLN (protein-losing nephropathy). In all Wheatens examined in the research study, these genes always showed the same patterns...
    • All dogs that were 1-1 for NPHS1 were also 1-1 for KIRREL2 (both copies each gene normal),
    • All dogs that were 1-2 for NPHS1 were also 1-2 for KIRREL2 (heterozygous for both genes),
    • All dogs that were 2-2 for NPHS1 were also 2-2 for KIRREL2 (both copies of each gene are variant).

In other words, the normal versions of these two genes were always inherited together, and the variant versions to these genes were always inherited together. Because of this it is not known with 100% certainly, which gene variant puts a dog at high risk for developing PLN, or whether or not they both act together (although, based on what is known about those two genes and proteins they encode, it is thought that NPHS1 is more likely).

Among the well over 4,000 Soft Coated Wheaten Terrier samples that Penn has analyzed since the test was introduced in 2012, there have been three (3) Wheaten terriers with results in which both genes had different genotypes, (for example 1-1 for NPHS1 and 1-2 for KIRREL2). In these cases, Penn reports the results more specifically, and discusses the ramifications of these results with the dog’s owner.

Penn's DNA testing continues to test both genes for two reasons. It is not 100% certain which of the two gene variants is most important in the PLN disease process and running two tests for each sample increases the quality control in the testing process. The websites of some commercial labs indicate that they only test for one of the genes, usually NPHS1.

2020 Defining the Effect of Genotype, Breed and Age on the Risk of Developing Canine Degenerative Myelopathy and Investigating the Molecular Mechanisms Underlying that Risk

The Endowment, together with the SCWTCA and the SCWT Genetic Research Fund is donating to the funding for AKC Canine Health Foundation Grant 02800: Defining the Effect of Genotype, Breed and Age on the Risk of Developing Canine Degenerative Myelopathy and investigating the Molecular Mechanisms Underlying that Risk. Together with mixed breeds and 30 other breeds, Wheatens are susceptible to DM, a late-onset progressive neurodegenerative disease. Read the joint funding effort PDF at the Endowment At Work page. Information about the grant is at news.htm and at https://www//.akcchf.org/research/research-portfolio/2800.html

2020 Genetic testing for Degenerative Myelopathy and Microphthalmia

The University of Pennsylvania's PennGen testing facility has announced the availability of genetic testing for DM and Microphthalmia, a condition involving eye abnormalities and blindness. Penn's research into PLN in Wheatens resulted in genetic testing for the variant alleles associated with risk of PLN and has been offering testing to owners since 2012. The Endowment, together with the entire Wheaten community, supported the research leading to the PLN testing. Owners can now obtain all 3 tests through PennGen. Read the PennGen announcement PDF at the PLN Testing Recommendations page.

2020 Dr. Paula Henthorn's June SCWT PLE/PLN Research Progress Report

1. Survey
A 91-question survey was developed and distributed (in three phases) to owners and breeders, beginning early this year. A single survey was sent for each of 3773 dogs that had been tested using the PLN-Associated Variant Genes Test (and thus, we have DNA for these dogs). We have had 883 completed responses, of 1204 surveys that have been started, and we are still accepting completed surveys (until June 14th, with extensions possible if people email Dr. Gentry and ask for the extension). We are examining information provided from the surveys, with the first goal of identifying the dogs that will be most useful for our studies and obtaining medical records for these dogs. This first step is underway, with the help of a Penn undergraduate pre-vet student intern, who will be contacting veterinary clinics to obtain medical records.

2. Sequencing dogs for studies of both PLE and PLN
The Animal Health Trust in England has sequenced two dogs, including one healthy 13-year-old SCWT. Sequencing of 10 additional dogs has been completed, and the data files transferred to our laboratory. All 12 of these dogs will be useful for the study of PLE, with some of the dogs also useful for studies that may enhance genetic testing for PLN. The analysis will go into full swing when we can get access to the computer that we need for the analysis. (All non-essential research was suspended starting March 18th, and limited access to our laboratories is now being phased in.)

3. GWAS (Genome Wide Association Study, using SNP chips)
This phase is on hold until we identify additional dogs for GWAS analysis, based on information from steps 1 and 2 above.

4. Offer additional genetics tests for use by SCWT breeders: (DM/Degenerative Myelopathy) and Microphthalmia.
Two genetic disease that have been identified in Wheaten Terriers are listed above. We have developed assays for these tests and now offer them through the PennGen laboratories. We have created two documents (one to announce the test availability, and one to explain the genetics of microphthalmia in SCWT, based on the study performed in Finland (Kaukonen et al. 2018 Cell Reports 23(9):2643-2652). To determine if this disease variant allele is present in the North American SCWT population, we tested 66 of the DNA samples derived from PLN testing. Fifteen percent (10 of 66 samples) tested as carriers for the disease-associated variant in the RPB4 gene. (Among these samples were 48 samples that were received after mid-November 2019. Five of these recent samples were carriers.) None of the 66 samples had two copies. This is a small sample size, but it does demonstrate that this disease-causing gene variant is present in the SCWT population. Genetic testing, particularly of any female that is being considered for breeding, will allow breeders to avoid affected puppies in their breeding programs.

Finances (by numbered activities above)
1. $15,500 was contributed from the SCWTCA and the SCWT Endowment ($7750 each) to cover salary for Dr. Mariah Gentry and for a student researcher. After Penn’s share of these gifts (note that the majority of these funds come to the School of Veterinary Medicine, thus indirectly supporting this work), $12,400 was available for our work. To date, $11,000 has be spent for Dr. Gentry’s salary. Dr. Gentry will be working on the project until the end of 2020. Funds needed in excess of $12,400 for Dr. Gentry and the student intern will be supplied from previous gifts to the project.
2. $10,000 was contributed from the SCWTCA and the SCWT Endowment ($5000 each) for ten dog genome sequences, with $8000 directly available for this project. The fee for sequencing 10 dogs was $8200, and less than originally quoted. Additional funds from previous donations be applied to the annual software fees for sequence and GWAS analysis software (annual fee of $3000).
3. The estimate of the cost for this part of the research was originally estimated at $10,000, although costs will be re-examined as the scope of the necessary work becomes clearer.
4. All costs for the development of the assays, and initial screening for microphthalmia were completely covered by the PennGen laboratories, including technician and faculty salaries. [PennGen is a genetic testing facility operated through the Section of Clinical Genetics and Advanced Therapies (CGAT) at the University of Pennsylvania's School of Veterinary Medicine. It is a not-for-profit laboratory offering testing for genetic diseases, primarily in dogs and cats, and other molecular diagnostic services, such as somatic mutation screening in cancer patients. Together with CGAT’s Genetic Disease Discovery Laboratory, PennGen also engages in research to uncover the genetic basis of a wide range of diseases in animals and offers metabolic screening for inborn errors of metabolism including inherited and acquired forms of Fanconi Syndrome, and electron microscopy for ciliary dyskinesia in dogs.]

Respectfully submitted, with thanks for your ongoing support,
Paula Henthorn, PhD
(Professor of Medical Genetics, University of Pennsylvania School of Veterinary Medicine)