Post by maggie on Feb 20, 2010 22:29:26 GMT -1
this is a note of today's meeting. I'll add the questions and answers as I get them typed up. Please add, amend and clarify as necessary as these are just my own notes and I may have missed things. It was a really good meeting and I'm very grateful to DPS Council for organising and for the experts who gave up their weekend to talk to us.
Talk to the Dales Pony Society on Foal Immunodeficiency Syndrome
Parish Hall, Barnard Castle
Saturday 20 February 2010
Speakers:
Professor Stuart Carter, Liverpool University
Laura Fox-Clipsham, Animal Health Trust (AHT)
Doctor June Swinburne AHT
Paul May MRCVS was in attendance for questions
The speakers were introduced by the DPS Chairman, Mr. Jeff Daley
Prof. Carter
An eminent immunologist, Stuart Carter BSc, PhD, FIMLS, is Associate Dean for Research at the University of Liverpool’s School of Veterinary Science. He has worked with Prof. Derek Knottenbelt on research into FIS since it was first recognised.
History
· Recognised in Fell Ponies in 1995 by Penrith Veterinary Investigation Centre
· Inherited genetic disorder
· Breeding history suggested that other breeds would suffer
· 2008 was the first confirmed diagnosis in Dales
Symptoms
· anaemia (photo of mouth of affected foal, gums almost white, not pink)
· ill thrift (failure to grow as normal)
· opportunistic infections – diarrhoea, nasal discharge, glossal (tongue) ulceration
Syndrome in Dales
· May 2008
· Immediately reported to Liverpool and AHT
· Foal admitted, diagnosed and euthanised
· Syndrome confirmed by pathology
Diagnosis
· From history and clinical signs
· Haematology – anaemia, lymphopaenia, neutrophilia
· No definitive test in the past
Signs of syndrome – for breeders
· Normal at birth
· Poor growth
· Recurrent infections from 3-6 weeks
· Do not respond well to treatment
Signs of syndrome – for vets
· Untreatable infections
· Dehydration
· Profound anaemia with PCV <20
· Neutrophilia
· Lymphopaenia
· Consider obtaining post-mortem results
Treatment
· Symptomatic – rehydrate, antibiotics etc.
· Administration of Lavamisole
· Blood transfusions etc.
NO TREATMENT IS EFFECTIVE – SYNDROME LEADS TO 100% MORTALITY
Severe anaemia
Graph here showing normal PCV levels at a relatively consistent 40% and affected foals starting at around 30% at 3 weeks and dropping over time to as little as 3%
Major breakthrough 2004
· Discovered the immunological problem and provided a test for possible diagnosis
· B Lymphocyte deficiency implicated
· Important because B cells make antibodies to fight infection
· Implications are that foals showing B cell deficiency inevitably succumb to infection when the maternal antibodies (from colostrum) have gone and this is consistent with Syndrome showing at 3 weeks + because they can’t make their own antibodies
Cause
· Inherited defect
· An autosomal recessive gene
· Spread is unobserved as no apparent detriment to the individual, therefore impossible for an owner to detect.
· Similar to genetic conditions in Irish Setter dogs, Holstein cattle and Arab horses
· Tests have been developed and the disease is under control in these breeds
Spread
· Only needs 1 animal to start
· Spread is silent
· Many carriers by the time of the first diagnosis
Genetic bottlenecks
· 1900 - Fells had a founder population of 30 animals and were subsequently cross bred with others, largely Dales
· 1940 – WW2, many ponies lost and not replaced post-war
Carrier numbers
· Fells have between 10%-22% born annually with Syndrome, so carrier rates are calculated to be 20% - 40% of overall population.
· Dales carrier rate could easily be 10% or more
Laura Fox-Clipsham
Research student at the AHT whose PhD study work has led to the breakthrough in finding a test for Syndrome
Aims of the study
· To identify the genetic mutation
· To develop a test in order to
o Detect syndrome foals
o Identify carriers
o Suggest breeding strategies/options
o Screen other breeds
The study
· Run by the AHT and University of Liverpool
· Funded by The Horse Trust and PetPlan
· Laura ran the genetic studies on the archive of samples provided by Dr. Gareth Thomas and Paul May MRCVS
Fells and Dales Ponies
· Native to the British Isles
· Both rare breeds on recognised by Rare Breeds Survival Trust
· Both proved to be affected by Syndrome
Autosomal
(autosomal means that it is not related to sex and both males and females can be equally affected)
· Only needs 1 founder animal
· The spread of the defective gene is silent
· Once detected, it is likely that there are many carriers
Inheritance
· 1 copy of mutant gene at the start
· some offspring inherit that gene
· at some point 2 distant relative, both carrying the gene, breed
· 2 copies of the gene mean a 25% chance of a Syndrome offspring
· the horse has 268 million bases (data points) on 31 chromosomes
· using samples from affected ponies, the search was narrowed
· Chromosome 26 showed a significant association
The Investigation
· Having identified the chromosome, there were still 3million bases to investigate
· This was whittled down to 1.2million
· Then it was possible to use the new ‘genome mining equipment’ bought by Liverpool in 2009
· Tests were concentrated on 5 animals and had to be done 50 times each x 1.2 million
· A number of candidate genes were identified and each was analysed until the mutation was identified consistently.
· Analysis showed it was possible to identify clear, carrier and affected conditions
Population study
· AHT held samples from both Fells and Dales that had been submitted for parentage profiling and these were tested
· 215 Fell samples showed 39% to be carriers
· 96 Dales samples showed 18% to be carriers
· 800 samples from other breeds will be tested before the end of the study
Naming
· important to break the link with one breed
· the disease will now be known as Foal Immunodeficiency Syndrome (FIS)
Test results
· First batch of results out this week
· Results will be shown as one of three categories
o Affected
o Carrier
o Clear
Breeding options
· Clear x clear = clear (100%)
· Clear x carrier = clear (50%); carrier (50%)
· Carrier x carrier = clear (25%); carrier (50%); affected (25%)
· Affected is a Syndrome foal which will inevitably die, so avoid carrier to carrier matings to avoid affected foals
Dr. June Swinburne
Researcher at the AHT and supervisor, with Prof. Carter, of Laura’s PhD study.
How to get the test
· Details on the AHT website www.aht.org.uk/genetics fis.html
· Or contact Angie Stagg on FIStesting@aht.org.uk
· Or get in touch with the breed society, FPS or DPS – this is the preferred route
The test will
· Distinguish clear, carrier and affected ponies
· 2 applications
o test breeding stock
o diagnose affected foals
Administration
· samples can be submitted via Breed Societies (preferred route as easier to administer) where batches of tests are returned to the societies for distribution to owners
· vets can take and submit the samples
· neither the breed societies nor the vets will know the results, the certificates showing status will be sealed for onward distribution to the owner. Only the owner will know the status of an individual animal
Sample
· tests are based on a hair sample
· this must be pulled, not cut
· sample to be submitted in an FIS sample bag supplied by AHT
· vet signs the bag to certify identity of animal and posts to AHT
· samples can be from archives held by breed societies and submitted by them
· tests results will normally be returned within 30 days
· foal samples will be fast-tracked and returned to vets by phone or email within 3 working days
· overseas samples can be tested, contact the breed society for details
Breeding strategy
· avoid carrier to carrier matings
· don’t exclude carriers from the breeding stock – restricting the gene pool will not be advantageous
· DPS Council will need to decide how to use the results of the tests
· Best advice is to gradually reduce the carrier numbers in the population
Talk to the Dales Pony Society on Foal Immunodeficiency Syndrome
Parish Hall, Barnard Castle
Saturday 20 February 2010
Speakers:
Professor Stuart Carter, Liverpool University
Laura Fox-Clipsham, Animal Health Trust (AHT)
Doctor June Swinburne AHT
Paul May MRCVS was in attendance for questions
The speakers were introduced by the DPS Chairman, Mr. Jeff Daley
Prof. Carter
An eminent immunologist, Stuart Carter BSc, PhD, FIMLS, is Associate Dean for Research at the University of Liverpool’s School of Veterinary Science. He has worked with Prof. Derek Knottenbelt on research into FIS since it was first recognised.
History
· Recognised in Fell Ponies in 1995 by Penrith Veterinary Investigation Centre
· Inherited genetic disorder
· Breeding history suggested that other breeds would suffer
· 2008 was the first confirmed diagnosis in Dales
Symptoms
· anaemia (photo of mouth of affected foal, gums almost white, not pink)
· ill thrift (failure to grow as normal)
· opportunistic infections – diarrhoea, nasal discharge, glossal (tongue) ulceration
Syndrome in Dales
· May 2008
· Immediately reported to Liverpool and AHT
· Foal admitted, diagnosed and euthanised
· Syndrome confirmed by pathology
Diagnosis
· From history and clinical signs
· Haematology – anaemia, lymphopaenia, neutrophilia
· No definitive test in the past
Signs of syndrome – for breeders
· Normal at birth
· Poor growth
· Recurrent infections from 3-6 weeks
· Do not respond well to treatment
Signs of syndrome – for vets
· Untreatable infections
· Dehydration
· Profound anaemia with PCV <20
· Neutrophilia
· Lymphopaenia
· Consider obtaining post-mortem results
Treatment
· Symptomatic – rehydrate, antibiotics etc.
· Administration of Lavamisole
· Blood transfusions etc.
NO TREATMENT IS EFFECTIVE – SYNDROME LEADS TO 100% MORTALITY
Severe anaemia
Graph here showing normal PCV levels at a relatively consistent 40% and affected foals starting at around 30% at 3 weeks and dropping over time to as little as 3%
Major breakthrough 2004
· Discovered the immunological problem and provided a test for possible diagnosis
· B Lymphocyte deficiency implicated
· Important because B cells make antibodies to fight infection
· Implications are that foals showing B cell deficiency inevitably succumb to infection when the maternal antibodies (from colostrum) have gone and this is consistent with Syndrome showing at 3 weeks + because they can’t make their own antibodies
Cause
· Inherited defect
· An autosomal recessive gene
· Spread is unobserved as no apparent detriment to the individual, therefore impossible for an owner to detect.
· Similar to genetic conditions in Irish Setter dogs, Holstein cattle and Arab horses
· Tests have been developed and the disease is under control in these breeds
Spread
· Only needs 1 animal to start
· Spread is silent
· Many carriers by the time of the first diagnosis
Genetic bottlenecks
· 1900 - Fells had a founder population of 30 animals and were subsequently cross bred with others, largely Dales
· 1940 – WW2, many ponies lost and not replaced post-war
Carrier numbers
· Fells have between 10%-22% born annually with Syndrome, so carrier rates are calculated to be 20% - 40% of overall population.
· Dales carrier rate could easily be 10% or more
Laura Fox-Clipsham
Research student at the AHT whose PhD study work has led to the breakthrough in finding a test for Syndrome
Aims of the study
· To identify the genetic mutation
· To develop a test in order to
o Detect syndrome foals
o Identify carriers
o Suggest breeding strategies/options
o Screen other breeds
The study
· Run by the AHT and University of Liverpool
· Funded by The Horse Trust and PetPlan
· Laura ran the genetic studies on the archive of samples provided by Dr. Gareth Thomas and Paul May MRCVS
Fells and Dales Ponies
· Native to the British Isles
· Both rare breeds on recognised by Rare Breeds Survival Trust
· Both proved to be affected by Syndrome
Autosomal
(autosomal means that it is not related to sex and both males and females can be equally affected)
· Only needs 1 founder animal
· The spread of the defective gene is silent
· Once detected, it is likely that there are many carriers
Inheritance
· 1 copy of mutant gene at the start
· some offspring inherit that gene
· at some point 2 distant relative, both carrying the gene, breed
· 2 copies of the gene mean a 25% chance of a Syndrome offspring
· the horse has 268 million bases (data points) on 31 chromosomes
· using samples from affected ponies, the search was narrowed
· Chromosome 26 showed a significant association
The Investigation
· Having identified the chromosome, there were still 3million bases to investigate
· This was whittled down to 1.2million
· Then it was possible to use the new ‘genome mining equipment’ bought by Liverpool in 2009
· Tests were concentrated on 5 animals and had to be done 50 times each x 1.2 million
· A number of candidate genes were identified and each was analysed until the mutation was identified consistently.
· Analysis showed it was possible to identify clear, carrier and affected conditions
Population study
· AHT held samples from both Fells and Dales that had been submitted for parentage profiling and these were tested
· 215 Fell samples showed 39% to be carriers
· 96 Dales samples showed 18% to be carriers
· 800 samples from other breeds will be tested before the end of the study
Naming
· important to break the link with one breed
· the disease will now be known as Foal Immunodeficiency Syndrome (FIS)
Test results
· First batch of results out this week
· Results will be shown as one of three categories
o Affected
o Carrier
o Clear
Breeding options
· Clear x clear = clear (100%)
· Clear x carrier = clear (50%); carrier (50%)
· Carrier x carrier = clear (25%); carrier (50%); affected (25%)
· Affected is a Syndrome foal which will inevitably die, so avoid carrier to carrier matings to avoid affected foals
Dr. June Swinburne
Researcher at the AHT and supervisor, with Prof. Carter, of Laura’s PhD study.
How to get the test
· Details on the AHT website www.aht.org.uk/genetics fis.html
· Or contact Angie Stagg on FIStesting@aht.org.uk
· Or get in touch with the breed society, FPS or DPS – this is the preferred route
The test will
· Distinguish clear, carrier and affected ponies
· 2 applications
o test breeding stock
o diagnose affected foals
Administration
· samples can be submitted via Breed Societies (preferred route as easier to administer) where batches of tests are returned to the societies for distribution to owners
· vets can take and submit the samples
· neither the breed societies nor the vets will know the results, the certificates showing status will be sealed for onward distribution to the owner. Only the owner will know the status of an individual animal
Sample
· tests are based on a hair sample
· this must be pulled, not cut
· sample to be submitted in an FIS sample bag supplied by AHT
· vet signs the bag to certify identity of animal and posts to AHT
· samples can be from archives held by breed societies and submitted by them
· tests results will normally be returned within 30 days
· foal samples will be fast-tracked and returned to vets by phone or email within 3 working days
· overseas samples can be tested, contact the breed society for details
Breeding strategy
· avoid carrier to carrier matings
· don’t exclude carriers from the breeding stock – restricting the gene pool will not be advantageous
· DPS Council will need to decide how to use the results of the tests
· Best advice is to gradually reduce the carrier numbers in the population
