Cystinuria Project FAQs

Auction to support project: November 13-20!

Who is the principal investigator?
Dr. Paula Henthorn is Professor of Medical Genetics and Chief, Section of Medical Genetics, at the University of Pennsylvania’s School of Veterinary Medicine.  Here is more information on Dr. Henthorn, including a list of her publications.

How will the money be raised for this project?
Plan A is to raise money through donations, which will be solicited on-line, by mail (to those without computers), and by telephone, as well as an on-line auction and possibly some clothing sales.

How much of the current Bunny Austin balance is being used for the project?
Currently the BAF has about $13,000. It is used for the annual sample collection and health test clinic, and we like to keep a few thousand in the fund so if we get a smaller request we have the money to do it: for instance, that’s how we funded Dr. Henthorn’s previous project to do a Whole Genome Sequence on a cystinuric Deerhound. If we get close to our goal after having asked everyone to donate and completed our auction and clothing sales, then Miranda Levin will go to the Board and ask for some Bunny Austin funds. We hope we don’t need to touch the Fund, but it’s there if we need it.

What happens to the donations made to Penn if enough money is not raised?
We have the money to cover any differences between what is raised and the grant total, so that is not an issue.

Can I see the grant proposal?
Here is the grant proposal submitted to the Health and Genetics Committee:

Proposal: Next Steps with Cystinuria Research in Scottish Deerhounds

As was reported in the year-end research report in The Claymore, the whole genome sequencing (WGS) of a cystinuric Deerhound has been done, and there were no obvious dominant or recessive mutations in the two known “cystinuria genes” (SLC3A1 and SLC7A9). Given that to date all of the known mutations that cause cystinuria in dogs have been found on one of those two genes, further research needs to be done to search for potential mutations in or near those genes before we can categorically say that we have to look elsewhere.
To accomplish this, we propose to:
1.     Update and expand Dr. Henthorn’s cystinuria research database to include health information (particularly cystinuria status) and pedigree information on any Deerhound that has DNA stored at the University of Pennsylvania. Specifically, with the help of veterinary students, we will:

a.     Ascertain all available DNA samples stored at the University of Pennsylvania, either through the cystinuria research or through Factor VII testing.
b.     Integrate all PennGen data (urine nitroprusside and DNA testing) into Dr. Henthorn’s cystinuria research database.

And with the help of the SDCA’s Health and Genetics Committee and veterinary students, we will contact by email or phone the owners of all dogs that have DNA stored at the University of Pennsylvania to:

c.     Obtain current health information and add this to the database.
d.     Obtain pedigree information and add this to the database.
e.     Recruit urine sample submissions (shipping materials and fees will be covered).
f.      Perform nitroprusside testing on urine samples and add the results to the database.
g.     Perform quantitative urine amino acid analysis on selected samples and add the results to the database.

2.     Use the cystinuria research database to assemble pedigrees that include cystinuric dogs (with emphasis on dogs that have blocked) and examine the pedigrees for evidence of single-gene modes of inheritance.

Perform WGS (20X coverage) on two stone-forming dogs to continue to search for the potential disease-causing mutations in two known cystinuria genes, including promoter and enhancers for these genes, as well as sequences outside of these genes that are suspected (in human and mouse) to control the expression of these genes and their chromosomal regions. We will also examine the genes for other amino acid transporters that may affect renal cystine transport, and genes that affect testosterone metabolism.  As controls, Dr. Kate Meurs has made available WGS data from four Scottish Deerhounds in her cardiomyopathy study.  We also have access to the list of sequence variants from >280 dog genomes in the sequence data from the “Dog Biomedical Variant Database Consortium”. If no suitable controls can be found in these already-sequenced dogs, then we will perform WGS (20X coverage) on a control dog.

The above will be done as a grant contract; the SDCA is required to send to Penn a letter that lays out the payment schedule, timeline, reporting responsibilities, etc.

The Penn Vet School is able to accept donations, which would be tax-deductible, directly from donors, but they will charge a 20% administrative fee on all direct donations. This 20% will go to the Vet School and not the project, and is not included in the grant budget as outlined in the proposal above. This will be made clear to all donors.

What is the study budget?
ITEM                                                                                                     COST                                    
Vet Student Research                                                                                                                    $13.17/hr, 2 students, 5 hr/wk, 5 weeks                                              $  660

Shipping costs (urine)                                                                                                          ~$30/package (supplies and fees), 50 samples                                 $1500

Amino acid quantitation (with shipping)                                                                                              15 samples @ $90                                                                                    $1350

Whole genome sequencing, 3 dogs @ $2100                                     $6300

Sequence analysis (Dr. Henthorn)                                                       $1550

Overhead (8%)                                                                                         $  909

TOTAL                                                                                                    $12,269

Who owns the research and the samples?
The University of Pennsylvania.

What is the timeline for the project?
The study has already begun and must be completed by December 31, 2017.

What about reports from Dr. Henthorn?
Complete and thorough progress reports that include a lay summary on the status of the research shall be prepared and provided in writing to the SDCA Health & Genetics Committee no later than December 31, 2016, and June 30, 2017. A final report that includes a lay summary shall be provided to the SDCA Health & Genetics Committee no later than December 31, 2017.

What recourse do we have if for some reason Dr. Henthorn doesn’t finish the project as outlined?
This is a grant contract with a letter of agreement signed by both parties. Dr. Henthorn and Penn are contractually obligated to finish this project. It’s the most protection we can get for a project of this type.

This is the next logical step in our cystinuria research as we search for the genetic mutation that causes this disease in Deerhounds. Once we know what that mutation is, we can develop a genetic test for it, which will help breeders make more informed breeding decisions. As we have said, Dr. Henthorn’s research in other breeds with this disease and research in human cystinuria would indicate that the mutation that is causing the problem in Deerhounds is on one of the two genes known to be involved in the other breeds and humans. So the chances are reasonable. However, this is scientific research, so full of surprises. But we won’t know whether the odds are with us or against us unless we look.

If you have any more questions or concerns, please don’t hesitate to ask — use the contact form below.

SDCA Health & Genetics Committee