Interview with Dr. Meryl Littman About The Informative Family Study
Tell us again the goal for the project … what do you hope to find out, how will we use that information first as breeders, then as owners.
SCWTCA Benchmarks March 2004
This project, Longitudinal Field Studies of Families of Soft Coated Wheaten Terriers Affected with Protein-Losing Enteropathy and/or Protein-Losing Nephropathy and the Foundation of a DNA Bank (more commonly referred to as the Informative Family Project), offers information to add to the important findings from the NCSU colony of Wheagles. Our dogs are out in the field, and include additional families from different geographical areas, having different exposures to infections, diets, medications, etc. and various genetic backgrounds. The study will follow close relatives of affected animals over their entire lives, and look for patterns of inheritance, timing of initial abnormalities found on screening tests, progression of disease, and possible effects of early intervention.
The study will collect large enough samples (not just cheek swabs) of DNA for the Bank from affected animals, their close relatives, and normal (presumably) geriatric animals. We will learn information about pedigrees and phenotype for each dog over its lifetime so that the genotypic information from the Bank will be meaningful. In order to identify markers in the future, we need larger samples of DNA than cheek swabs. Once markers are found, check swabs may be fine for testing, but cheek swabs are not enough for researchers to use to search for the genes involved or for markers, which will ultimately help the breeders in their decision-making.
This is a frustrating time because the Open Registry is not completely helpful and there are no predictive tests or markers yet for these serious diseases affecting 10-15% of the SCWT community. The pressure for information to come out within a few years is intense. Anecdotal information usually comes to light before statistical analysis results are satisfactory for evidence-based medicine. The rush for anecdotal information before we are really sure may ultimately hurt the breed, because animals may be culled prematurely (decreasing genetic diversity) or puppies may be put on diets or medications that possibly could mask their true phenotypes.
I urge breeders to be patient because most answers will not be forthcoming until we have followed the full life spans of the members of informative families and allowed the geneticists to do their work on the samples. We need to wait for informative family members to live out their full life spans (they are not like short-lived mice) and learn their phenotypes (expression of health or illness).
I can give an example of how early information may be of use to breeders/owners. Suppose a diet change rumored to delay manifestations of disease does not, then we may realize that food allergy may not be primary, but secondary or coincidental with the disease process. Or suppose the recommended screening tests (fecal API and ERD or Up/c) reveal abnormalities, possibly just outside normal range, this early information may prompt breeders, owners, and their veterinarians to repeat the test sooners than they might otherwise, and allows all involved to consider using interventions to slow progression of the disease.
How many families and how many dogs are involved in the study?
We currently have 3 families, plus the NCSU colony dogs as the 4th family. There are about 60 dogs in the longitudinal study. We have room for more because 2 of our 3 families are small. New informative families for the Bank are most likely to be found if breeders have already saved frozen tails, identified individually. Then, when an affected dog is found with a littermate that has already died, the samples will already be available for the Bank and this family can be polled for further participation.
In one of our families, we have most of the DNA samples already, including the affected litter and many ancestors, even with some representation from great-grandparents! This is important because the geriatric samples from our informative families will be very helpful to our studies. In this family, the affected dogs are middle-aged and often female, as in the previous findings. One side appears more affected so far than the other, which may go along with either a dominant or recessive inheritance.
In another of our families, we only have a few of the DNA samples we hope to get. The litter affected is unusually young, most are already affected, and there are more males affected in the family than we usually find. Again, the older generations are not showing as high an incidence of the diseases. The mode of inheritance in this family so far goes along with recessive inheritance. We will learn a great deal as the ancestors of this young affected litter age join the study.
The third family is new to the study and is a small family (just litter, sire/dam; no aunts/uncles/grandparents). We have most of the DNA samples because the breeder saved puppies’ tails/dewclaws. There are males and females affected. Interestingly, the grandparents, although not participating, have lived past 10 years of age. Again, a recessive mode of inheritance appears likely.
Dr. Shelly Vaden is participating in our studies. The affected SCWT family and the extended Wheagle family in the colony at NCSU are included in the DNA Bank.
Do you have everyone you need?
A few members of the first early families have not fully participated as yet, despite the owners’ early positive intentions to do so. We expect those samples to still come, hopefully this year. If they are not forthcoming, those families will not yield as much information as we had hoped they would.
We are still looking for another informative family or two. When new affected dogs are identified (either from consultations or OR), we try to find out if the breeder is able/interested in helping with adding that family to our studies. If they have kept good records, and especially if they have kept tails in their freezers, the family would be useful to our studies. Sadly, many breeders are unwilling to help, even though the Dockers project helped to identify families of interest.
Are dogs from different parts of the country?
So far the West and Midwest are represented, as well as Canada via the NCSU line. Some dogs live in other areas of the country as well. I don’t feel the need to look for any particular geographic area; in fact, Eastern dogs may confuse the issue because of Lyme nephropathy as a possibility causing PLN.
Are there any tests besides CBC, Chemscreen, urinalysis, urine protein/creatinine ratio, and fecal API testing being conducted?
Those are the tests that the AKC grant covers. Other tests are sometimes recommended during consultations with the veterinarians taking care of sick dogs.
How often are samples collected?
The plan is to have all dogs tested annually. Participants can have free screening each year by sending samples to Penn, or they may choose to have testing done by their local veterinarians and send test results to me. Our goal is to have them continue monitoring and keeping close watch on their dogs and contact us concerning any health issues.
Can you describe the process?
Styrofoam box kits were sent to participants so that the samples will arrive in as good condition as possible. The kit contains instructions for the owners and their veterinarians, as well as tubes, gel packs, FedEx papers, consent forms, and the outer Styrofoam box. The first year the blood sample for DNA is collected, as well as the samples for screening tests. For subsequent years, only samples for screening are sent. If dogs become ill, consultations are freely given. If dogs succumb, samples are also taken after death, with the owner’s permission.
How are SCWTCA members helping?
The main way SCWTCA members have helped is to educate each other about the importance of the studies, about the use of screening tests, and to share information openly without cultivating rumors. Health Committee members have worked very hard to find cooperating breeders of the informative families. Health Committee members have made themselves available to answer the myriad of questions about health that are coming from the SCWT community, because Shelly Vaden and I cannot possibly answer them all. The article in Benchmarks encouraged breeders to save puppy tails/dewclaws in readiness for the DNA Bank so we might gain information from those families if a member should become affected. Two of the families we are following already saved samples of DNA from many members.
How does the geriatric information you are receiving from owners of healthy old dogs fit into the project?
The geriatric dogs are VERY important for the project because we will compare the genotype/phenotypes of normal to abnormal in the SCWT breed. The best “normals” would be the close relatives of the “abnormals,” but this is not always possible. In several of the informative families, many of the members are affected and we don’t have as many normal genotypes as we’d like to have for comparison. Or sometimes, a relative might have appeared to be normal, but died prematurely (before the golden age of 14-16 years) due to hit by car, cancer, etc., and we don’t know whether if the dog had lived longer it might have shown an abnormal phenotype eventually. Samples from the geriatric animals in the informative families (parents/grandparents) would be “excellent” for the DNA Bank; getting information from other “normal” geriatric SCWT dogs is still “very good” for future genetic studies.
Is there anything the breeder community can do to help with the Informative Family Project?
Thank you for helping! Getting cooperation has been harder than any of us thought it would be. Please, breeders, keep saving those puppy tails/dewclaws in your freezer (with each one identified) and keep good records of the puppy owners, their contact information, and keep email contact every year at “birthday” time to see how they are doing. These communications will be a source of additional informative families to watch and include in the Bank.
Please step forward to help or when asked to help, please don’t hold back. Paula has said that hundreds of samples of DNA from people with cancer have allowed for genetic markers to be found. So I’d like this generation of breeders to help us add as many “affecteds,” “normals,” and small informative families as possible to our SCWT DNA Bank. We don’t want the next generations of breeders to have to worry about this. Let’s fill the Bank with gusto so our geneticists will have lots of samples to work with, now that the research technology is available. Thanks.
