september 20071 1. the research team 1.1. introduction 1.2. canine models 1.3. collaborations 1.4....

September 2007 1

1. The Research Team1.1. Introduction1.2. Canine models1.3. Collaborations

1.4. Statement from Dr. Hannes Lohi

2. Genetic Research Study: Epilepsy in Dalmatian Dogs:2.1. Most needed items2.2. Confidentiality of data

3. Collected samples

4. Expectations from this study

5. Links & contacts

Genetic Research Study: Epilepsy in Dalmatian DogsGenetic Research Study: Epilepsy in Dalmatian Dogs

CONTENTSCONTENTS

September 2007 2

1.1. Introduction: Research team of canine models of human inherited diseases (University of Helsinki, Faculty of Medicine)

Research Leader: Dr. Hannes LohiAdjunct Professor,Academy Research FellowLeader of the Canine Epilepsy Consortium in Europe

Research Team:Raevaara Tiina, PhDSeppälä Eija, PhDHytönen Marjo, MScJokinen Päivi, MScAhonen Saija, BScKorhonen Anu, BScKyöstilä Kaisa, BScEklund RanjaLoikkanen Anna Ritala Marjut

Dr. Hannes Lohi

1. RESEARCH TEAM1. RESEARCH TEAM

September 2007 3

human disease genes

1.2. CANINE MODELS1.2. CANINE MODELS

dogs help finding human disease genes

September 2007 4

Proven model:Lafora-Disease in humans

( 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 geneEPM2B, EPM2A

Miniature-wired-haired-dachshund

and basset hounds:Chromosome 35

Humans:Chromosome Nr. 6

September 2007 5

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. COLLABORATIONS1.3. COLLABORATIONS

1.3. COLLABORATIONS1.3. COLLABORATIONS

September 2007 6

• 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 Lohi21.03.2007:


1.4. STATEMENT1.4. STATEMENT

September 2007 7

Info from breeders/owners about affected dogs (also of dead dogs)

blood samples (affected dogs, their siblings and close relatives)

epilepsy questionnaire

financial support


2.1. MOST NEEDED ITEMS2.1. MOST NEEDED ITEMS

September 2007 8

affected dogs per litter

sex of affected dogspedigree

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


INFO FROM BREEDERS/OWNERSINFO FROM BREEDERS/OWNERS

September 2007 9

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


BLOOD SAMPLES FOR DNA ISOLATIONBLOOD SAMPLES FOR DNA ISOLATION

September 2007 10

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)


GENE LOCALISATION/DNA MARKERGENE LOCALISATION/DNA MARKER

September 2007 11

sibling of affected dog(healthy)

affected dog

affected dog, far related easing the detection

just a few different genes

just a few same genes



September 2007 12

affected dogs



DNA marker: can be tested straight away

in humans

September 2007 13

- 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


EPILEPSY QUESTIONNAIREEPILEPSY QUESTIONNAIRE

September 2007 14

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.


2.2. CONFIDENTIALITY2.2. CONFIDENTIALITY

September 2007 15

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/


FINANCIAL SUPPORTFINANCIAL SUPPORT

September 2007 16

41 DNA samples of affected

dalmatians incl. 11 sib-pairs*

*(=effected dal + healthy sibling)


3. COLLECTED SAMPLES3. COLLECTED SAMPLES

FINLANDU.S.A.

EUROPE

September 2007 17


EXPECTATIONSEXPECTATIONS

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

September 2007 18

Canine Genetic Research in Finland, Autumn 2006 ( http://www.koirangeenit.fi/ )

contact:Research Leader:[email protected]

Information in english/german:http://www.epidal.dalmatiner.org)

contct. [email protected]


4. LINKS & CONTACTS4. LINKS & CONTACTS

Text & slide design: Bettina Hutz, Review & responsible for the scientific contense: Dr. Hannes Lohi

september 20071 1. the research team 1.1. introduction 1.2. canine models 1.3. collaborations 1.4....

Documents

research team slide

genetic background of

research groups

dalmatian dogs info

dalmatian dogs contents

europe research team

canine models dogs

canine epilepsy consortium