but it is what it is. As I stated before, I am no expert and we now have to let science prove what it will prove. I have asked Lisa Shaffer at Paw Print Genetics to introduce herself and to add to what I have already said and asked her to share the current status of the project and what will be done going forward. Please keep an open mind and know that this project was started because I love and care about our breed. It is my greatest hope that in the near future, no other Chinese Crested will have to suffer the unpredictability of seizures, because of EP and the distress it causes them. It is also my greatest hope by being honest and trying to be a leader, not a follower, when it comes to health issues—that more people will be will- ing to come forward with information and be willing to share problems they have seen in their breeding programs. It is no ones fault that EP is becoming a major health concern in our breed as we have no test—but we all need to take note and make health our number one priority again and stop breeding for ribbons. What good is a CH or lots of pretty ribbons when our dogs are not healthy? In most cases of seizures or Epilepsy in our breed, age 3-5 is when most sei- zures are being reported to have start- ed. Many of our dogs are already being bred by this age so each one of us needs to be diligent in researching any health problems behind our dogs. According to the pedigree research I have done, affected dogs from breedings that have parents that are NOT affected can/usu- ally produce a single affected pup. Now, if you have a dog that is not affected but has produced affected (or have affect- ed relatives or produce affected) and breed it to a dog that is or later becomes affected, usually that breeding will pro- duce 2 or more affected offspring from the breeding. I have also seen affected dogs bred that have not produced any affected offspring. With this being prov- en consistently, across the board for all dogs I know that are affected—this is my reason for thinking EP in our breed is recessive. Now we just have to wait for the science to prove what it will! I hope that my thinking and research is not correct because if it is, my calcula- tions show that our breed is going to be in trouble in the near future. Many peo- ple are using the same popular studs and popular pedigrees knowing that
region in the genome likely to con- tain ‘The Mutation’—again, assuming one mutation. Now that the genome of about 3 billion base pairs of DNA and roughly 20,000 genes has been narrowed to smaller regions that may contain the mutation, we are now per- forming linkage analysis on 10 pedi- grees collected. In these pedigrees, we have collected affected dogs, their parents and in some cases, the normal siblings. The DNA from the dogs in these pedigrees will be used to hone- in on ‘The One Region’ likely to con- tain the mutation. From there, we will examine the genes in the region and choose those that are likely candidates for the EP gene. Candidates include genes that are expressed in the brain or work in pathways known to also carry mutations in humans resulting in EP. Once candidate genes are cho- sen, we will sequence those genes in hopes of identifying a mutation (a change in the DNA) that is found only in affected dogs and their obligate car- rier parents, but not found in normal relatives (unless they are carriers) and not found in unrelated, healthy dogs. Once the mutation is identified, we will then develop a diagnostic test at Paw Print Genetics to screen large numbers of dogs to identify carriers and prove that other affected dogs have the same mutation. It may be that some EP dogs do not have our yet-to-be dis- covered mutation, but have a mutation elsewhere in the genome. It is quite possible that dogs have more than one mutation that contributes to EP. But it is also possible that the mutation found in the Chinese Crested will also be found to contribute to EP in other breeds. So our hope is that the work that we are doing in Chinese Cresteds can also help dogs of other breeds. This research could not be done without the support of Chinese Crested breeders and owners. We are grateful for Karen Fischer-Smith for bringing this important concern to our attention, for getting people involved and espe- cially for helping people obtain swabs and submit samples to us. Her dedica- tion and the dedication of the owners and breeders who have submitted sam- ples is what keeps us going in our pur- suit of the answers. Know that you are not only helping your breed but you are helping to provide a better understand- ing of EP in all dogs.
some of these dogs and combinations have produced Epilepsy—but yet it seems most are willing to take a chance. I hope that chance is worth it. a feW Words from the expert Lisa G Shaffer, PhD, FACMG Founder & CEO, Paw Print Genetics Spokane, WA As founder and CEO of Paw Print Genetics, I am very interested in all aspects of canine health. I have a PhD in human genetics, which allows me to use my knowledge of human genet- ics and apply that to canine genetics. In humans, there are several thousand mutations known to cause disease; whereas there are only a few hundred mutations known in dogs. We hope to improve canine health by identifying additional mutations that cause canine disease and epilepsy is one of them. Epilepsy (EP) is a clinical term to describe recurrent, abnormal brain activity that manifests as seizures. There are many causes of EP and even within the genetic, or inherited causes, there are likely many gene mutations that might contribute to EP. Think of the genome as a set of blueprints. The genome codes for proteins that provide the building blocks for cells and con- trol the functions of those cells. Genes do not work in isolation; genes work in pathways. Imagine that there are probably hundreds if not a few thou- sand genes that must work together for proper brain function. That is why, when you enter the word ‘epilepsy’ into the Online Mendelian Inheritance in Man (http://www.ncbi.nlm.nih. gov/omim) database, you get over 700 hits on conditions that have isolated EP or EP in combination with other clinical features. The goal of our research is simple— find the gene and causative mutation that is causing EP in Chinese Crested dogs. Based on pedigree examination, ‘The Cause’, may actually be more than one mutation. However, to approach this problem, we have assumed one gene mutation causes the EP that is found in the pedigrees that we are using. From the cheek swab samples that have been collected, we extract- ed DNA (the genomic blueprints) and together with researchers from TGEN, have performed a genome wide asso- ciation study (GWAS) to identify the
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