Epilepsy and Pneumonia/PCD Update

Dr. Margret Casal, Section of Medical Genetics, School of Veterinary Medicine, University of Pennsylvania

We are looking forward to a busy summer and fall of data analysis.  As we write this, exciting new experiments are underway to detect DNA sequence differences at places in the dog DNA where more that one different base is known to occur in different dogs.  We call sequence differences polymorphisms. The particular polymorphisms we are working with are called SNPs (pronounced "snip") for single nucleotide polymorphism. Our experiments are being performed using the recently developed "SNP chips". This work is possible through generous funding from the Irish Wolfhound Studies, Inc and with statistical support from the Penn Genomics Frontiers Institute (PGFI). A core facility within PGFI is currently performing SNP chip analysis on 300 dogs, including nearly 100 Irish Wolfhounds in the epilepsy study, using the Affymetrix 127K SNP-chip.

So, what is a SNP chip, what are we looking for in the data, and where do we go from here? To make a SNP chip, MANY short synthetic DNA molecules (called oligonucleotides or "oligos"), representing alternative DNA sequences known to occur in dog DNA, are individually attached to a small piece of silicon glass (about the size of your thumbnail) in a precise gridded pattern. These oligos, attached on one end to the silicon chip, are free to selectively bind to pieces of a dog's DNA that perfectly match them. Based on the pattern of binding of the dog's DNA to the grid of different oligos, each dog's DNA sequence at the sites of DNA variation can be detected and recorded.

Once the data is collected, we will start the analysis, in which we will look for instances when affected dogs have the same DNA sequence and unaffected dogs show variability at the same SNP. If we find this type of association, we will have identified the region of the dog genome (genome means all of the DNA in a cell) that contains a gene that is associated with epilepsy. By analogy, let's imagine that the DNA in the dog genome is represented by Interstate 80, spanning the United States. If we find an association between a particular SNP and epilepsy, we will know which state the gene is in. Our next task will be to find out which exit to use in that state. If we can find the exit, we should be able to develop a genetic test that will detect dogs carrying a DNA sequence that puts them at risk for developing epilepsy.

So why are we going to be analyzing for several months? Because we will be able to look at more than 120,000 different SNPs, in almost 100 dogs (remember that each dog has two copies of every gene or SNP). That is more than 24 million pieces of data that must be analyzed in multiple different ways. The SNP technology and the types of statistical analysis that will work best for dogs have not yet been well established, so we will be charting new territory. This new technology is potentially very powerful, and will ultimately benefit the Irish Wolfhound and other dog breeds not only for the study of epilepsy, but for many other simple and complex diseases, such as PCD and lymphoma. (note: PCD samples are now being examined using the same technique.)

Margret Casal, Dr. med. vet., Ph.D., Dipl ECAR
Paula Henthorn, Ph.D., professor medical genetics

Reprint requests to:
Margret L. Casal Dr med. vet, PhD or Paula Henthorn, Ph.D., professor medical genetics
E-mail: swampsyde26@att.net

Two Noted Researchers Join IWF Research Committee

The Research Committee of the Irish Wolfhound Foundation is pleased to announce the addition of two distinguished scientists to its roster. Both Dr. Margret Casal and Dr. Nathan Sutter are highly-respected researchers committed to helping Irish Wolfhounds and their owners.

MARGRET CASAL, Dr. VET. MED., PH.D.,
Diplomate EUCAR

Dr. Margret Casal, Assistant Professor of Medical Genetics at the University of Pennsylvania School of Veterinary Medicine, performed the seminal research characterizing idiopathic epilepsy as an inherited disease in the Irish Wolfhound. In addition, she continues working on characterizing PCD, pneumonia, and recurrent pneumonia in wolfhounds.

NATHAN B. SUTTER, PH.D.

Dr. Nathaniel B. Sutter, Assistant Professor of Medical Genetics at the Cornell University School of Veterinary Medicine, heads the Sutter Dog Genetics Laboratory there. In 2007, Dr. Sutter’s work identifying a DNA regulatory sequence which reduces the activity of a growth gene in dogs, completed while he was a research fellow at the Ostrander Laboratory at the National Institute of Health, received national attention because of its implications to human genetics. Since 2004, Dr. Sutter has been assisting the IWF Research Committee with establishing a DNA Blood Bank for use in genetic research of benefit to IWs.

Please Help Us Find the Genes That Cause
Irish Wolfhound Bone Cancer

The Irish Wolfhound Foundation is working with leading geneticists to help identify the gene(s) involved with bone cancer. We know that cancer, whether hereditary or not, is a disease of genes. But we don’t know which set of genes malfunction when an Irish Wolfhound gets osteosarcoma.

If you have a wolfhound diagnosed with bone cancer, we need a blood sample from your dog. We also need more blood samples from wolfhounds eight years of age or older who have never had any type of cancer.

This blood will go into our own Irish Wolfhound DNA blood bank, which the IWF established in 2004 in order to support research specifically designed to help our breed. Blood is stored at the Ostrander Canine Genomics laboratory at the National Institutes of Health and at the Sutter Dog Genetics Lab at the Cornell University Veterinary School. This is NOT the same as CHIC, so if your dog’s blood is in CHIC and you would like to help, you will need to give another blood sample.

We will supply you with blood collection tubes, mailing canisters, and simple instructions for your vet. All you need to do is complete the included release form, attach the mailing label, and send it back with your dog’s blood sample. Contact Karen Malone at iwpaw@verizon.net if you would like to participate, or, if you have further questions, call Kathy Wilson at (252) 257-2525.

Thank you for supporting the critical research that is our best hope for fighting osteosarcoma in our beloved hounds.

New IWF-Sponsored Study To Evalualte IW VPC Arrhythmia

The Irish Wolfhound Foundation is funding a new research study by veterinary cardiologist Dr. William D. Tyrrell, Jr., and resident cardiologist Dr. Gina Pasieka as chief investigators. The goal of their research is to characterize ventricular premature contractions (VPCs) in wolfhounds who have no underlying heart disease.

Ventricular premature contractions (VPCs) are heart rhythm disturbances that interrupt the normal heart rhythm and cause an irregular beat. While one or two isolated VPCs can be harmless, when they occur very often or repetitively, they can lead to a very serious condition called ventricular tachycardia. For this reason, all dogs with VPCs should be closely monitored.

In Boxers and Dobermans, VPCs can signal a condition which frequently leads to sudden death. In wolfhounds, VPCs appear to be more benign. However, VPCs have been found in wolfhounds with impaired cardiac function as well as those with no heart disease.

Twenty wolfhounds will be evaluated. Drs. Tyrrell and Pasieka will collect data from echocardiograms, electrocardiograms, bloodwork, thyroid tests, and tick panels. They will then have each dog wear a holter monitor to record a 24-hour continuous EKG.

This study will give us a much better idea of whether or not VPCs are truly benign in wolfhounds, or whether they can indicate more serious problems.

If your IW‘s EKG has had VPCs please consider entering your IW in this study. Contact Kathy Wilson at (252) 257-2525 or kathywilson25@gmail.com.