1. September 20071 1. The Research Team 1.1. Introduction 1.2. Canine models 1.3. Collaborations 1.4. Statement from Dr. Hannes Lohi 2. Genetic Research Study: Epilepsy in Dalmatian Dogs: 2.1. Most needed items 2.2. Confidentiality of data 3. Collected samples 4. Expectations from this study 5. Links & contacts Genetic Research Study: Epilepsy in Dalmatian Dogs CONTENTS

2. September 20072 1.1. Introduction: Research team of canine models of human inherited diseases (University of Helsinki, Faculty of Medicine) Research Leader: Dr. Hannes Lohi Adjunct Professor,Academy Research Fellow Leader of the Canine Epilepsy Consortium in Europe Research Team: Raevaara Tiina, PhD Seppälä Eija, PhD Hytönen Marjo, MSc Jokinen Päivi, MSc Ahonen Saija, BSc Korhonen Anu, BSc Kyöstilä Kaisa, BSc Eklund Ranja Loikkanen Anna Ritala Marjut Dr. Hannes Lohi 1. RESEARCH TEAM

3. September 20073 human disease genes 1.2. CANINE MODELS  dogs help finding human disease genes

4. September 20074 Proven model: Lafora-Disease in humans ( Hannes Lohi et.al, Science, 2005)Hannes Lohi et.al, Science, 2005 Mutation in gene Epm2b Epm2b becomes ” un-readable” Lack of malin enzyme  problems in glycogen branching Starch accumulates in brain, neuronal damage EPILEPSY Mutation in gene EPM2B, EPM2A Miniature-wired- haired-dachshund and basset hounds: Chromosome 35 Humans: Chromosome Nr. 6

5. September 20075 Dr. Hannes Lohi collaborates: - with other Research Groups worldwide - with The Missouri Research Group (USA)  Dr. Lohi has access to dalmatian DNA samples and pedigrees that have been collected by the Dalmatian Club of America.  For the first time ever there is a chance to track the genetic background of Epilepsy in Dalmatians and the possibility to develop a gene-test. 1.3. COLLABORATIONS

6. September 20076 dalmatians suffer from epilepsy, in Finland and in other countries too comparison of Finnish and US data show similarities:  genetic background : seems to be ”quite simple”  onset-age : varies from other breeds (24 weeks - 9,9 years)  genes can be carried through many generations unseen  no breeder can know if he/she breeds with a carrier  dalmatians epilepsy occurs also in outcross combinations (EU-USA)  gene –test can be developed now with new technologies  more samples and information is needed Dr. Hannes Lohi 21.03.2007: Genetic Research Study: Epilepsy in Dalmatian Dogs 1.4. STATEMENT

7. September 20077  Info from breeders/owners about affected dogs (also of dead dogs)  blood samples (affected dogs, their siblings and close relatives)  epilepsy questionnaire  financial support Genetic Research Study: Epilepsy in Dalmatian Dogs 2.1. MOST NEEDED ITEMS

8. September 20078 affected dogs per litter sex of affected dogs pedigree possible way of inheritage & amount of genes, breed specific background(?) amount of possible involved genes better breeding recommendations better planning of research study epilepsy questionnaire Genetic Research Study: Epilepsy in Dalmatian Dogs  INFO FROM BREEDERS/OWNERS

9. September 20079  from dalmatians which suffer from epilepsy  from their healthy siblings, and close relatives (minimum required: 20 sib-pairs = affected dogs + 1 healthy sibling)  from old and healthy dogs that never showed any symptoms of epilepsy Genetic Research Study: Epilepsy in Dalmatian Dogs  BLOOD SAMPLES FOR DNA ISOLATION

10. September 200710 blood DNA SNP array chips affected dog healthy sibling SNP arrays are:  a way to detect genetic variations within a population  used to study complete loss of an allele or from an increase in copy number of one allele  making it possible to detect the smallest mistakes in genetic information  containing the complete genetic information of dogs!  expensive (300 Euro one chip) Genetic Research Study: Epilepsy in Dalmatian Dogs GENE LOCALISATION/DNA MARKER

11. September 200711 sibling of affected dog (healthy) affected dog affected dog, far related  easing the detection just a few different genes just a few same genes Genetic Research Study: Epilepsy in Dalmatian Dogs GENE LOCALISATION/DNA MARKER

12. September 200712 affected dogs Genetic Research Study: Epilepsy in Dalmatian Dogs GENE LOCALISATION/DNA MARKER DNA marker: can be tested straight away in humans

13. September 200713 - age - sex - relatives - onset-age - phases before/during/ after seizures clinical examinations treatment & medication - dosing - efficiency - side.effects - EEG - CT - MRI general info - blood tests - diagnose seizures & seizure phases relation to breed specific (?) genetic background  optimization of treatment & medication - life-style Genetic Research Study: Epilepsy in Dalmatian Dogs  EPILEPSY QUESTIONNAIRE

14. September 200714 Any information given is important for the research team in order to get an idea about the heritage of epilepsy in our breed and for developing a gene-test. It is out of the question that this info will be misused for creating suspicions on breeders or single dogs of those days, or of the past. It is important to look forward and giving breeders the tool for avoiding epilepsy in the future without relying on rumors or suspicions. No club and no person outside Dr.Lohi´s research team will ever get to know, which dogs and which breeders are involved. Genetic Research Study: Epilepsy in Dalmatian Dogs 2.2. CONFIDENTIALITY

15. September 200715 The Hereditary Diseases Research Support Association (PeSaTu)/ Finland  a non-profiting, fund raising organisation formed by: Finnish Association of Veterinarians, The Finnish Breeders Association, The Finnish Nova Scotia Retrievers Association, The Great Pyrenees and The Pyrenean Shepherds Association and Shetland Oy goals: funding, fostering and promoting canine genetic research of hereditary diseases Funds: from private and institutional donors, raised by membership fees, direct donations and fundraising activities More info: http://www.pesatu.fi/ Genetic Research Study: Epilepsy in Dalmatian Dogs  FINANCIAL SUPPORT

16. September 200716 41 DNA samples of affected dalmatians incl. 11 sib-pairs* *(=effected dal + healthy sibling) Genetic Research Study: Epilepsy in Dalmatian Dogs 3. COLLECTED SAMPLES FINLAND U.S.A. EUROPE

17. September 200717 Genetic Research Study: Epilepsy in Dalmatian Dogs EXPECTATIONS What can we get out of this study? storage of DNA the ”amount” of epilepsy inside our breed better understanding of different ”types” of epilepsy breed specific factors way of inheritage possible breeding recommendations optimization of medication, treatment, life-style factors gene test  clear identification of carriers and non-carriers  breeders don´t have to take risks  epilepsy can be avoided  gene pool can be kept larger i

18. September 200718 Canine Genetic Research in Finland, Autumn 2006 ( http://www.koirangeenit.fi/ )http://www.koirangeenit.fi/ contact: Research Leader: hannes.lohi@helsinki.fi hannes.lohi@helsinki.fi Information in english/german: http://www.epidal.dalmatiner.orghttp://www.epidal.dalmatiner.org) contct. epidal@dalmatiner.orgepidal@dalmatiner.org Genetic Research Study: Epilepsy in Dalmatian Dogs 4. LINKS & CONTACTS Text & slide design: Bettina Hutz, Review & responsible for the scientific contense: Dr. Hannes Lohi