A Gentle Reminder

Clifden Show week is beginning on Sunday.  This is a time when much purchasing of Connemara Ponies has been the norm. The genetic test for HWSS will not be available before the end of the  year, so any pony buyers will still need to use visual criteria to assess whether a pony is HWSS affected or not; there is no way of physically assessing carrier status.

So here are a few suggestions for onsite assessment:

• Only consider young stock and/or breeding ponies presented without shoes and without hoof black. 
• Be extremely wary of ponies which are shod and not in work, especially youngstock.
• Do not accept any reasons/excuses about the farrier 'trimming the feet too short the last time he/she was out'.  Feet that are too short is a 'red flag'.
• Any chipping or peeling away of the outer hoof wall is a red flag.
• Pick up the feet yourself and have a look at the structure of the hoof wall between the white line and the outer hoof wall (see photo below).
• Look at the environment the ponies are living in. Boggy conditions masks the issue.
• Hoof black can be used to hide the use of hoof fillers - shod and hoof blacked 'red flag'.

For those purchasing from a distance (ie not personal inspection or through an agent) ask for not only conformation photos and videos, but close up pictures of feet - unshod and not blacked, and taken with the pony standing on concrete.

Here is a picture which demonstrates that the splitting occurs within in the structures of the hoof wall and not at the white line.  This photograph comes from a Swedish HWSS site with many good quality photographs of HWSS feet.  Even with short and newly trimmed feet (a prime method used to attempt to disguise HWSS), any sign of fissures should be classed as a 'red flag'.  Normal feet do not do this.

Another important factor to consider is the genetic inheritance of the pony/ies you may wish to buy. The higher the level of inbreeding, the higher the chances are of ponies carrying recessive genes.

Checkout An Analysis of the Sire Lines Represented in the 2013 CPBS Class 1 Stallion List if you want to found out just how dire the inbreeding issue is.

General News Updates

Those readers of the blog who also follow the HWSS Facebook page will already know that last month the number of hits on the blog reached 20,000 - this total has been reached in 19 months of operation.  As of right now the hits are 20,570.  There has been big upsurge in traffic, especially from Ireland.  As the number of hits from Ireland does not even register in the top ten source countries, which is deemed to indicate a low internet presence, this increase in traffic may be in part due to the following:

 DoneDeal advertisement

To whomsoever paid for and listed this advertisement the Irish Connemara Pony breeders should be grateful. From the perspective of the global community the significance of the HWSS issue does not seem to be understood in the heartland of Connemara pony breeding.  

It is a proven fact that continuing to ignore the existence of a genetic disease will do far more harm to the sales market than accepting that there is indeed a problem and doing something positive about it.  This has been proven in the past in the case of both HYPP and HERDA.

Linked to the incidence of  the expression of genetic disease in any population is the level of inbreeding in that population.    Deirdre Feely in her 2003 paper Characterisation of the Connemara Pony Population in Ireland states the following - the highlights are those of this blog editor:

"Following the analysis, it appears that the Connemara Pony breed is being confronted with two problems. Firstly, the survival of the traditional type of breed is under threat, and secondly, the genetic diversity of the breed is diminishing.

Today, the riding industry is an important outlet for Connemara Ponies. However, there is concern that this industry is instigating a shift from the traditional type of pony, to a taller, ‘modern’ type. The traditional type of Connemara Pony is perfectly adapted to the environment in which it developed and is completely distinct from other equine breeds. It may be necessary to safeguard against market forces inciting the disappearance of the traditional type of pony, which is a valuable national resource, and once lost can never be recovered.

The results generated from the characterisation of the Connemara Pony population indicate that past breeding practices have caused a significant loss in the breeds’ genetic diversity. To ensure that the genetic variation in the breed does not recede to a detrimental level, breeding policies need to be altered.

In future, it is vital that sire family sizes become more balanced, giving all stallions a better opportunity to breed their own replacements in the next generation. This would help to control the level of inbreeding and genetic diversity within the population.

The stallions used for breeding are closely related to each other and tend to be of similar ancestry or breeding lines. From a genetic diversity perspective it may be advantageous to have a pool of breeding stallions that are less related to each other to bestow a variety of genes to the proceeding generations.

As relationships among animals in the present population is high the mating of related animals is inevitable. Breeders must be very vigilant in respect to the stallions that they use for breeding to ensure that a minimal amount of inbreeding is practised.

There are 16 different countries, outside Ireland, that have formed their own Breeders’ Societies and maintain their own stud books. A study is presently being undertaken to characterise the Connemara Pony populations in a number of these countries. It is hoped that these animals may be a source of genetic variability that could be used to widen the gene pool of the Irish Connemara Pony population.

Adequate genetic diversity is vital for the long term health and viability of any population. Thus, it is vital that breeding practices are altered in order to secure the future prosperity of the Connemara Pony breed.'

Sadly this advice does not appear to have been taken on board by the majority of the ruling elite within the pony breeding community worldwide, not just in Ireland.  

Analysis of the genetics of the Connemara pony in all of the countries where the ponies are bred is presently underway.  If the issue of  over used bloodlines and stallions is not addressed then we can expect to see the incidence of new emerging genetic disorders to rise.   

HWSS is potentially the 'canary in the mine' - an indicator of what is to come for the breed if fundamental changes are not made now, about the selection of breeding stock to reduce the level of in-breeding.  Over use of popular or fashionable stallions is the leading cause in-breeding and subsequent population decline.  

There has to be a shift in outlook from just breeding the next generation, to looking as to what will happen in three to five generations, if this breed is to survive in a healthy state for future pony owners and breeders to enjoy.

The results of this work to date can be read on the new website Connemara Pony Genetics International  Comments and questions on the presented papers is encouraged and contributions for publication are invited.

Another new site has also recently been started Connemara Pony Breeders/Producers of Ireland, Chat & Debate where hopefully discussions of importance will not be censored as has happened in the past on other sites.

HWSS research has been officially presented to the world.

The team from Bannasch Laboratory were involved  in the recent 10th International Equine Genome Mapping Workshop  held  10-13 July 2013 at the Biotechnology Centre of Azores from the University of Azores. 

The First International Equine Gene Mapping Workshop sponsored by the Dorothy Russell Havemeyer Foundation (DRHF) was conducted in 1995 in Lexington, Kentucky. Since then, a series of horse genome workshops were conducted by the DRHF every two years (San Diego, California; 1997; Uppsala, Sweden; 1999; Brisbane, Australia; 2001; Kreuger Park, South Africa; 2003; Newbridge, Ireland; 2005; Tahoe City, California; 2007; Ickworth, Suffolk, United Kingdom; 2009; Chaska, Minnesota; 2011).

Over 200 scientists from 20 countries around the world have been participating in these workshops, sharing ideas and resources, collaborating and creating a common genomics framework.

The Bannasch submission is as follows:

10th Dorothy Russell Havemeyer Foundation International Equine Genome Mapping Workshop Abstract

A successful genome wide association for Connemara Hoof Wall Separation Syndrome using the equine Illumina 74K beadchip

Danika Bannasch, Carrie Finno, Carlynn Stevens, Amy Young, Sheila Ramsay

A syndrome has been described in Connemara foals characterized by severe separation of the hoof wall during the first year of life.  Clinical signs of HWSS occur when the weight-bearing borders of the hoof wall break away from the underlying structure, leaving the pony to bear weight on the sole of the hoof and unfit for riding.  Initial pedigree research has revealed a likely hereditary component to the disease with an apparent autosomal recessive mode of inheritance.   DNA samples, pedigrees and photographs were collected from Connemara ponies from around the world.  Within a year, 15 affected individuals and 315 controls were sampled.  Twelve cases and 24 controls were genotyped on the Illumina Equine 74K beadchip.  Based on our results, 12 affected and 24 unaffected cases provided significant power to identify a strong, genome-wide significant, candidate region of association (p raw 6.9 X 10^-11, p genome 2.6 X 10^-5).  Three additional affected foals and 5 obligate carriers were subsequently genotyped.  A region of homozygosity of 1.8 Mb was identified in all 15 affected foals consistent with an autosomal recessive mode of inheritance. Next generation sequence data from affected ponies and controls across the region will be analyzed for mutations and the results reported at the meeting.



The take home message from the information in the above abstract is that:

• There is NO DOUBT WHATSOEVER that HWSS is genetic in origin.  
• There is NO WAY that the above abstract would have been accepted for this workshop if the work being presented  was not proven beyond all doubt.
• HWSS is NOT the result of 'mineral imbalance', any other environmental challenge or lack of care of the part of owners of affected ponies.
• HWSS is the result of mating two ponies who carry a genetic mutation.

Denial that the cause of this condition is genetic is not going to make the problem disappear; indeed based on present trends the incidence of HWSS in the Connemara pony population is set to increase. 
A population genetics study presently underway, indicates that this is especially so in Ireland; a direct result of overuse of certain stallions both historically and in the present.

Guest Post by Tom Ryan FWCF on his experience with treating an HWSS affected pony.

This paper has recently been published in Forge Magazine and is republished here with kind permission from Mr Ryan http://www.equinehoof.co.uk/hwss.php

Hoof wall separation syndrome in Connemara ponies

Tom Ryan FWCF

The first time I saw pony Liam (name changed) was just after my client had bought him. I could see that he had slightly broken up hooves but thinking like most farriers would, I expected his hooves would improve under my charge. Unfortunately, this was not to be the case and as the winter progressed his hooves gradually deteriorated and by April 2010 the stratum externum was breaking away from the stratum medium, not just in the area around the nails but also around the toe of the hoof, an area that normally stays intact when hooves break up.

Photograph 1:  Liam's broken hoof in May 2010

As all four hooves were badly affected and thinking that a bacterial infection was causing the problem I decided to ask the help of the client's vet and together we took biopsies from the affected areas of Liam’s hoof wall. The results came back as normal, no abnormal bacteria associated with breaking hooves were found in the hoof.

Photograph 2:  Broken hoof removed and hoof poulticed with iodine

We decided that the entire areas of broken hoof should be removed but doing this to all four hooves at once was out of the question as it would make the pony very lame. Instead we decided to treat one hoof per week, in this way if we encountered problems it would be with only one foot. So each week all the broken hoof from one foot was removed and for the next twenty four hours the hoof was poulticed with iodine to ensure the hoof was sterile.

Photograph 3:  Kerckheart Aluminium shoe glued to repaired hoof

The hoof was rebuilt with glue then an aluminum shoe was glued to the repaired hoof, blue children's modeling dough was used on the inner border of his shoe to prevent the glue or shoe pressing onto the sole of his foot.  This was time consuming and expensive but worked well. For the next few months the glued on shoes were replaced as they started to become loose or were lost altogether, Liam was comfortable in the shoes and they didn’t cause him any problems.

Photograph 4: All hooves repaired

I noticed his hoof reacted slightly differently to the glue, in that the surface of stratum medium adhered less well to the glue, something I had not observed in other types of broken hooves. I have experienced cases of breaking hoof walls and seedy toe in other breeds both in everyday practice and as a referral farrier at an equine veterinary practice and I can safely say that Liam’s feet were different, although at the time I wasn’t sure quite how, it certainly was not a case of severe seedy toe.

When the wall had re-grown down to the ground surface, I could still see that his hoof was still not normal but tried again using nailed shoes, unfortunately his hooves soon started to deteriorate again. In discussion with the client it was decided to try Liam barefoot as an alternative solution to the problem but Liam soon became very uncomfortable and foot sore, as all his weight was being carried by his sole, as the hoof wall was crumbling away, we realised that this was not going to solve his problem and went back to gluing his shoes.

Liam had been bought for showing but as his feet were repaired with glue and the rules for showing do not allow filled or rebuilt hooves, he could not be shown. Considering that the only way of keeping him sound was with rebuilt hooves and glued shoes, meant his hooves were going to be a perpetual and very costly problem. After a lot of soul searching, the owner in discussion with her vet decided he would have to be put down.

It was eighteen months later at a Farriers Focus Day, that a farrier who has produced a horseshoe for broken hooves called GluShu[ii] first mentioned hoof wall separation syndrome in Connemara ponies to me. Some quick research on the internet[iii] revealed that there did seem to be an ongoing hoof wall problem within the Connemara population which some were calling ‘Hoof Wall Separation Syndrome‘(HWSS). Gauging what proportions of Connemara's have had problems or how severely it has affected them was difficult to establish, certainly some severe cases have eventually resulted in euthanasia.

Some contributors reported an apparent absence of lipids in HWSS affected hooves, a type of fat normally found in hoof, its function is thought to provide protection to the hoof structure by repelling excess moisture. Reading the comments of others about HWSS, I knew that this was what I had been dealing with eighteen months earlier.

Current thinking is that HWSS is a congenital genetic problem, the genes thought to be responsible are said to be recessive within an autosomal chromosome, autosomal chromosomes are not responsible for deciding the sex of the animal and therefore both males and females can carry the defective gene. Both parents must be carriers of the defective recessive gene in order to produce a chance of a foal with affected hooves. The possible outcomes are; a 1:4 chance that the foal will have HWSS, a 2:4 chance of a foal with good hooves but still a carrier of the defective gene and a 1:4 chance of producing a foal which is not a carrier and has good hooves.

Diagram 1:  Possible outcome if both parents are HWSS carriers. 

These chances are random and any outcome is possible for each foal born.

If one parent is a HWSS carrier and the other is not, then there will be a 2:4 chance of the foal being a carrier but it will not have HWSS hooves.

Diagram 2: Possible outcome if one parent is a carrier

The genome for the horse was sequenced for the first time in 2007, opening the opportunity to isolate which genes may be involved in HWSS. Currently research into HWSS is being carried out by Dr. Carrie Finno, DVM, PhD at University of California Davis and is focused on identifying the genes which are associated with the production of keratin, the protein which is used to produce horn and hair. DNA samples of both normal and affected animals are currently being collected and compared. The goal of this research will be the ability to identify carriers of HWSS with a simple blood test. So they can be isolated and excluded from any future breeding program (* editor's note). Until then it will only be when an affected foal with HWSS is born that it will alert the breeder that its parents are both carries of HWSS. As this may not be the first foal from this dam and sire, previous foals may have already been produced and unknowingly sold on, as there were no indicators at that time there was a genetic problem.

When only a few ponies were carriers the chances of both parents being affected must have been small, the odd foal with poor quality hooves would have been seen as a random occurrence of bad luck. Other foals would have been born as carriers with good hooves, in this insidious way HWSS has secretly crept into the population and as the ponies have moved around the world, so has HWSS. Today cases have been reported in many countries including UK, Ireland, Sweden, New Zealand and the USA.

From the one case that I have experienced, Liam's problems were of a greater magnitude than any broken hoof I had met before. The only solution to avoid future cases of HWSS will come from revised breeding practices which acknowledge the underlying genetic causes. If the first-class reputation of the Connemara is to be upheld, then both breeders and individuals will have to address this problem in an open and honest way.

First published in the Connemara Chronicle Vol 40-2013, page 183

Anatomy notes

The hoof wall is comprised of tubules of keratin which grow downward from the Coronary band. Distribution or the density of the horn tubules reduces through the three main zones of the hoof wall, the stratum externum, stratum medium and stratum internum. The greatest density of horn tubules is in stratum externum where on the surface of the hoof wall they are slightly flattened to become oval, which is thought to help retain moisture. The stratum medium forms the bulk of the hoof wall while the inner stratum internum has the lowest number of horn tubules and forms the laminal interface with the dermal tissues, it is usually un-pigmented and can be seen as a white line on darker coloured hooves

Diagram 3, Anatomy of hoof wall

Between the horn tubules is inter-tubular horn which binds the horn tubules together, this has intermediate filaments which are laterally orientated fibres which help to bind the horn tubules together and resist cracking.

The outer stratum externum is more rigid than the more flexible stratum medium, while the stratum internum is the softest, this gradient of reducing stiffness helps the hoof capsule transfer energy smoothly between the wall and the dermis and also allows the hoof capsule to expand in shape under loading and return back to it's original shape when the load is removed. Transfer of weight from the skeletal structures is primarily from distal phalanx (pedal bone) via the hoof wall to the ground surface, the solar surface can only support a small proportion of the total weight of the horse before it causes pain.

---

Footnotes:
[i] Jameg ShoeGlu, Jameg Horseshoes, Barnby Moor Stables, Kennel Drive, Barnby Moor, Retford, Notts., DN22 8QU

[ii] GluShu, https://www.facebook.com/glushu

[iii] Google "Hoof wall separation syndrome in Connemara ponies"

* Editor's note.  Removing carrier ponies from the breeding population is not recommended as this will further reduce an already truncated genepool; the test will identify carriers.  This information will help breeders to choose non-carrier mates and therefore prevent the production of any further affected ponies.

The relevance of the Fell Pony Syndrome Research to HWSS

The situation with HWSS in presently facing the breeders of Connemara Ponies is very similar to that which The Fell Pony breeders are faced with and which they have dealt with in a positive, constructive and successful manner.   The united approach to find cause of FIS  is an example that the Connemara Pony breeding community could well do to follow.  The whole of the latest research paper has been reprinted below because it has become obvious that people are not aware of how relevant this work is.  The blog stats tell us whether people outclick to the posted links; not one outclick has been made to this paper.

The overall population numbers are different between the Fell Pony situation described here and that of the Connemara Pony situation but the level of penetrance of the relevant mutations within in each of these  populations is very similar.  Table 1 at the end of the paper  makes for very interesting reading.

April 13, 2013 | Veterinary Record
Foal immunodeficiency syndrome: carrier testing has markedly reduced disease incidence

S. D. Carter, L. Y. Fox-Clipsham, R. Christley, J. Swinburne

Foal immunodeficiency syndrome (FIS), a fatal autosomal recessive disease found in three breeds of horses, was first reported (in the Fell pony) in 1996, and it soon became apparent that significant numbers of syndrome foals were being born each year. In each FIS case, the foals are clinically normal at birth, but start to weaken at 2–8 weeks (Scholes and others 1998) as they develop profound anaemia (Dixon and others 2000) and do not have the ability to produce their own antibodies (Thomas and others 2005), due to the almost total lack of B lymphocytes in the circulation or tissues (Thomas and others 2003), but with apparently normal levels of functional T lymphocytes (Bell and others 2001). The outcome is persistent opportunistic infections with no effective treatment; euthanasia is the preferred option. FIS has also been reported in Fell ponies in The Netherlands (Butler and others 2006), Germany (May and others 2011) and USa (Gardner and others 2006). In 2009, we confirmed a case of FIS in a Dales pony foal (Fox-Clipsham and others 2009).

The search for the genetic lesion thus became paramount, as the carrier parents were clinically normal, and it was feared that there could be high carrier rates in breeding Fell and Dales ponies. In 2009, we identified a single nucleotide polymorphism (SNP) in a sodium transporter (SlC5a3) which was completely associated with FIS and was homozygous in FIS foals and heterozygous in FIS carriers (Fox-Clipsham and others 2011a). The SNP is a functional alteration in an exon within the SlC5a3 gene, and within three months, we developed and launched a diagnostic test (available at http://www.animaldnadiagnostics.co.uk) based on PCR and sequencing to identify FIS carriers and early syndrome foals. This was made available to all equine owners and can be performed simply on pulled hair samples, removing the need for blood sampling.

The acquisition of the FIS test meant that we could identify carriers and make recommendations concerning the possible outcomes of specific breeding combinations, for instance, a carrier breeding with a normal pony, or two carriers breeding together. We regularly met with Fell and Dales pony owners to explain how they should use the FIS test to avoid producing a syndrome foal, and stressed the need to use the FIS test to avoid carrier-carrier matings. Concerns about depletion of the gene pool in pony breeds were soon quelled once it was explained that they could still safely use carrier ponies to breed with normal ponies. Indeed, it was pointed out that owners and breeders actually needed to widen their use of stallions to reduce the numbers of FIS foals and to preserve the gene pool.In the first year of testing, our fears were confirmed when the FIS carrier rates were shown to be 39 per cent in breeding Fell ponies and 18 per cent in breeding Dales ponies. Broadening the testing to other at-risk breeds (known to crossbreed with Fell and Dales ponies), showed that 1 per cent of a coloured pony population were carriers (Fox-Clipsham and others 2011b). There may be other breeds containing FIS carriers; only further population testing will confirm or deny this possibility.

The next key question was how effective the carrier test would be in reducing the numbers of FIS foals being born in subsequent years. There have now been two breeding seasons (2011 and 2012) prior to which the 

owners could avail themselves of the test and avoid carrier-carrier matings. The test findings (Table 1) provide considerable hope for the future.The FIS carrier rate in breeding adult Fell and Dales ponies varies over the three years of testing, but this variation was statistically significant (X2(2df) p=0.3, and Fisher’s Exact Test p=0.6, respectively). 

Importantly, there was a lower number of FIS-positive (diseased) Fell pony foals in 2011 and 2012 (although this only approached statistical significance (X2(2df) p=0.1, X2for trend (1df) p=0.08) and no FIS 

cases in Dales ponies in 2011 or 2012. Obviously, the datasets may be skewed because of the animals selected for testing, which may introduce some bias. However, as many carriers will have been identified previously from breeding records, there is no reason to suppose that FIS-positive breeding stock would be preferentially submitted. It is clear that the owners and breeders have taken the advice we provided about avoiding carrier-carrier matings, and that this has led to a major reduction in the number of syndrome foals born in the last two year. Although the definitive figures are not available, the total  number of breeding Fell ponies that have been FIS tested in the last three years (n=1171) comprise a large proportion of the breeding population, and the testing has been done to guide breeding strategies. By the same measure, the 284 Dales ponies tested represent a large part of  the breeding population of that breed.

Predictably, our breeding recommendations to use carrier-clear matings have not had a rapid impact on the large numbers of FIS carriers in the breeding populations of both breeds. Reducing carrier numbers will either take much longer using the current breeding approach, or a change in breeding strategy to avoid breeding from carriers at all. With the carrier rate so high in the Fell ponies, such a restrictive recommendation would probably be unacceptable to many  breeders, and would risk depleting the gene pool. On the other hand,  the breeders who choose carrier-clear matings will need to test their offspring to see if their foal is a carrier. The results are consistent with uptake of the FIS carrier test by the owners of at-risk ponies, and suggest that they have also taken our advice about breeding strategies to reduce the numbers of FIS-positive foals. This is a significant and swift impact of modern genomic technologies in clinical veterinary medicine, and is a healthy indicator of veterinary scientists and animal breeders working well together to improve animal welfare.

TABLE 1: Foal immunodeficiency syndrome (FIS)-positive test results in Fell and Dales ponies (adults and foals) (N/A=not applicable)

Year	Number tested	Normal (%)	FIS Carriers (%)	FIS Diseased (%)
(A) Fell ponies
Adults        2010	565	290 (51)	275 (49)	N/A
2011	179	103 (58)	76 (42)	N/A
2012	106	60 (57)	46 (43)	N/A
Foals          2010	142	72 (51)	58 (41)	12 (8)
2011	108	60 (56)	39 (36)	1 (1)
2012	71	32 (45)	38 (54)	1 (1)
(B) Dales Ponies
Adults 2010	180	158 (88)	22 (12)	N/A
2011	53	44 (83)	9 (17)	N/A
2012	36	32 (89)	4 (11)	N/A
Foals 2010	10	9 (90)	0 (0)	1 (10)
2011	4	3 (75)	1 (25)	0 (0)
2012	1	1 (100)	0 (0)	0 (0)

References
BELL, S. C., SAVIDGE, C., TAYLOR, P., KNOTTENBElT, D. C. & CARTER, S. D.
(2001) an immunodeficiency in Fell ponies: a preliminary study into cellular responses.
Equine Veterinary Journal 33, 687–692
BUTLER, C. M., WESTERMANN, C. M., KOEMAN, J. P. & SLOET VAN
OLDRUITENORGH-OOSTERBAAN, M. M. (2006) The Fell pony immunodeficiency syndrome also occurs in the Netherlands: a review and six cases. Tijdschrift Voor Diergeneeskunde 131, 114–118
DIXON, J. B., SAVAGE, M., WATTRET, A., TAYLOR, P., ROSS, G., CARTER, S. D.,
KELLY, D. F., HAYWOOD, S., PHYTHIAN, C., MACINTYRE, A. R., BELL, S. C.,
KNOTTENBELT, D. C. & GREEN, J. R. (2000) Discriminant and multiple regression
analysis of anaemia and opportunistic infection in Fell pony foals. Veterinary Clinical
Pathology 29, 84–86
FOX-CLIPSHAM, L., BROWN, E. E., CARTER, S. D. & SWINBURNE, J. E. (2011b)   Population screening of endangered horse breeds for the foal immunodeficiency syndrome mutation. The Veterinary Record 169, 655–655
FOX-CLIPSHAM, L., CARTER, S. D., GOODHEAD, I., Hall, N., KNOTTENBELT, D. C., MAY, P. D. F., OLLIER, W. E. & SWINBURNE, J. E. (2011a) Identification of a
mutation associated with fatal foal immunodeficiency syndrome in the Fell and Dales pony. PLoS Genetics 7 135, e1002133
FOX-CLIPSHAM, L., SWINBURNE, J. E., PAPOUlA-PEREIRA, R., BLUNDEN, A. S., MALALANA, F., KNOTTENBELT, D. C. & CARTER, S. D. (2009) Immunodeficiency/anaemia syndrome in a Dales pony. The Veterinary Record 165, 289–290
GARDNER, R. B., HART, K. a., STOKOl, T., DIVERS, T. J., FLAMINIO, M. J.,
JElINEK, F., FALDYNA, M. & JASURKOVA-MIKUTOVA, G. (2006) Fell pony syndrome in a pony in North america. Journal of Veterinary Internal Medicine 20,
198–203
MAY, A., LEIPIG, M. & GEHlEN, H. (2011) Case report of a Fell pony immunodeficiency syndrome foal in Germany. Pferdeheilkunde 27, 507–513
SCHOlES, S. F., HollIMAN, A., MAY, P. D. & HOLMES, M. A. (1998) a syndrome of anaemia, immunodeficiency and peripheral ganglionopathy in Fell pony foals. The Veterinary Record 142, 128–134
THOMAS, G. W., BELL, S. C. & CARTER, S. D. (2005) Immunoglobulin and peripheral B-lymphocyte concentrations in Fell pony foal syndrome. Equine Veterinary Journal 37, 48–52
THOMAS, G. W., BELL, S. C., PHYTHIAN, C., TAYLOR, P., KNOTTENBELT, D. C.
& CARTER, S. D. (2003) Aid to the antemortem diagnosis of Fell pony foal syndrome by the analysis of B lymphocytes. The Veterinary Record 152, 618–621

S. D. Carter, BSc, PhD, FRCPath
L.Y. Fox-Clipsham, BSc, PhD
R. Christley, BVSc, MVCS, PhD, 
DipECVPH, MRCVS
Department of Infection Biology,
Department of Epidemiology and
Population Health,
Institute of Infection and Global Health,
School of Veterinary Science, University
of Liverpool, Liverpool, UK
L. Y. Fox-Clipsham, BSc, PhD
Centre for Preventative Medicine,
Animal Health Trust, Newmarket, UK
J. Swinburne, BSc, PhD
Animal DNA Diagnostics Ltd,
William James House, Cowley Road,
Cambridge CB4 0WX, UK
E-mail for correspondence:
scarter@liv.ac.uk
Provenance: Not commissioned;
externally peer reviewed
Accepted February 14, 2013

Research Update

• A descriptive case report covering the clinical signs of HWSS and the pedigree research has been submitted for publication to the relevant, top peer reviewed journal available.  This paper has been accepted subject to some re-writing requests by the peer reviewers.  Such re-writing requests is normal procedure for peer reviewed publications.  Once the research paper has been published the on-line address for the abstract will be posted on this blog.

• a paper written by Tom Ryan (FWCF)  has been accepted for publication by Forge.  Forge the industry magazine for farriers and is sent to all farriers in the UK and by subscription to others around the world.  Tom has indicated that once publication in Forge has occurred he will be sending the paper to be circulated via this blog.  In his paper he deals with the issues of  hoof care to maintain quality of  life for HWSS affected ponies.

• The Havemeyer Foundation sponsored  10th International Equine Genome Mapping Workshop   is taking place in July in Portugal.   The Bannasch Laboratory will be there presenting their latest research on the HWSS issue.  Participants are invited to this prestigious workshop; just getting an invite to attend is an honour in itself.  To be one of the presenters validates the research work done to date.

• Over the summer the humongous quantity of data generated by the genomics work will be analysed in depth.  The computing requirements for such work is in the multi-terabyte arena, which is way beyond the capacity of all but a few computers in the world.  To access such a facility computer time has to be booked in advance. Booking ahead is a best guess option as to time scale and is judged on when a facility was needed in similar areas of research. As it turns out because the initial answers were so cut and dried on the HWSS project, the research has run ahead of the expected schedule. Further rapid progress has been constrained because of the need to wait for this pre-booked computer access.

• Another native pony breed with a genetic problem - The Fell has posted an update on their progress.  Their research to find the genetic marker commenced in 2005 with the mutation being located in 2009.  The test became available 3 years ago in 2010.If you wish to read more about the Fell pony research below are some links.  The process is quite proscribed. 

1. The first step is to publicise the emergence of a new condition to the veterinary profession; Immunoglobulin and peripheral B-lymphocyte concentrations in Fell pony foal syndrome.  
2. One then demonstrates that the problem is not confined to one geographical area but extends through the total genepool; The Fell pony immunodeficiency syndrome also occurs in the Netherlands: a review and six cases. 
3. The genetic research is performed and reported and published; Identification of a mutation associated with fatal Foal Immunodeficiency Syndrome in the Fell and Dales pony.
4. Having found the mutation the effects at the cellular level can be established; Fell Pony syndrome: characterization of developmental hematopoiesis failure and associated gene expression profiles.
5. The outcome; Foal Immunodeficiency Syndrome: carrier testing has markedly reduced disease incidence or put another way A recent report shows what can be achieved when scientists and horse breeders work together

• When one looks at the timescale involved with the  HWSS research much has been achieved in a very short time.  Unlike the situation with HWSS, the Fell Pony Syndrome (FPS) research had the backing, financially, morally and ethically from the Fell Pony Society and the Rare Breeds Trust; it also involved a large 'buy in' from the breeders themselves. 

The Connemara Pony Research Group would like to think that the scientific progress in this research is now sufficiently advanced that all societies, breeders and owners will now take this problem seriously and start making plans on how we as a community are going to use this information to preserve and protect our beloved Connemara pony. It is our hope that the CPBS and the ICCPS will see fit to invite Dr Carrie Finno to Ireland this year to present her HWSS research at an open public forum during  the Clifden Festival in August 2013.

Feel free to offer comment and helpful suggestions on the HWSS Facebook page.HWSS (Hoof Wall Separation Syndrome)

News from the Bannasch Laboratory

A message from the lovely people of the Bannasch Laboratory at U C Davis arrived today. 

"The Connemara community has been incredibly supportive, and I know you have worked extraordinarily hard at getting DNA to the lab. Your efforts and the generosity of many owners has been very effective, and we are no longer in need of control samples." 

This is a real kudos to the people who got in behind this project, both with donations to fund the work, and those who at their own expense, rallied to the call and submitted blood samples from their ponies. The research has come such a long way in a very short space of time (from the scientific research perspective). This would never have happened so quickly without you all.

Please note that samples from additional confirmed HWSS affected ponies will still be accepted.  

To anyone who wishes to send blood samples from outside of the USA from affected ponies, you are asked to wait until further notice whilst the import permits are renewed. Once the permits have come through, a notice to this effect will be posted on the blog.

Once again, thank you to all of the people who have made this research a 'happening thing'.

New Update - some good, some sad.

Sadly another pony has had to be euthanased because of intractable hoof pain from HWSS.  This pony was bred in Connemara, purchased at Clifden and exported to Sweden.   All four legs from this much loved pony have been sent to the Farrier School in Sweden for research and teaching purposes.  She was one of the ponies whose blood sample was sent over for the part of the research which proved that HWSS is indeed genetic in origin.

It is coming up to the time of the Pony Inspections in Ireland, where in the past much purchasing of Connemara Ponies has been the norm. The genetic test for HWSS will not be available before the end of the northern summer, so any pony buyers will still need to use visual criteria to assess whether a pony is HWSS affected or not; there is no way of physically assessing carrier status.

So here are a few suggestions for onsite assessment:

• Only consider young stock and/or breeding ponies presented without shoes and without hoof black. 
• Be extremely wary of ponies which are shod and not in work.
• Do not accept any reasons/excuses about the farrier 'trimming the feet too short the last time he/she was out'.  Feet that are too short is a 'red flag'.
• Any chipping or peeling away of the outer hoof wall is a red flag.
• Pick up the feet yourself and have a look at the structure of the hoof wall between the white line and the outer hoof wall (see photo below).
• Look at the environment the ponies are living in. Boggy conditions masks the issue.
• Hoof black can be used to hide the use of hoof fillers - shod and hoof blacked 'red flag'.

For those purchasing from a distance (ie not personal inspection or through an agent) ask for not only conformation photos and videos, but close up pictures of feet - unshod and not blacked, and taken with the pony standing on concrete.

Here is a picture which demonstrates that the splitting occurs within in the structures of the hoof wall and not at the white line.  This photograph comes from a Swedish HWSS site with many good quality photographs of HWSS feet.  Even with short and newly trimmed feet (a prime method used to attempt to disguise HWSS), any sign of fissures should be classed as a 'red flag'.  Normal feet do not do this.

Other news is that the final shipment of blood samples for HWSS research  has been dispatched from Germany.  A total of 184 ponies have contributed to the population study part of the research.  Well done Germany for have such pro-active breeders and pony owners.  In addition to the samples from the Connemara ponies, samples were included  from Highland ponies and Haflinger horses which demonstrate a similar hoof phenotype to that seen and known to be HWSS in Connemara ponies.  The farriers in Germany are to be commended for making the connection with the HWSS they are dealing with in Connemara ponies owned by their clients, and notifying the German research group representative about these other suspicious hooves.  Thanks must also go to the owners of these non Connemara ponies for being so willing to send samples to UC Davis.   

IF these breeds do show up as being HWSS affected it is the hope of the research group, that their relevant breed societies will be pro-active in dealing with the issues and not emulate the 'head in the sand' attitude which has been the predominant response from the Connemara breed 'authorities' with which the research group has to date met with.

One shipment of samples from Ulster has just safely  arrived at the laboratory for the population study.  30 ponies from a wide variety of bloodlines, one of which is a Scottish bred pony.  This shipment is the only one which has been sent from anywhere in Ireland.  Thank you to this pony owner for making the effort and shouldering the cost all on your own; this is appreciated by the researchers.

Dr Carrie Finno Receives an Award for Her Research

Dr Carrie Finno is the lead researcher who worked upon finding the genetic basis to HWSS for us.  She also was part of the team which found the genetic cause of HERDA.  

This year's James M. Wilson Award was presented to Carrie Finno, DVM, PhD, Dipl. ACVIM, for her work on neuroaxonal dystrophy (NAD), an inherited neurologic disease that affects all breeds of horses. The Wilson Award is given each year to an outstanding equine research publication authored by a graduate academic student or resident in the UC Davis School of Veterinary Medicine. Finno received the award for her publication, "Electrophysiological Studies in American Quarter Horses with Neuroaxonal Dystrophy."
You can read the full article here:
Dr. Carrie Finno Receives 2012 Wilson Award

The Connemara Pony Research Group congratulates Dr Finno on this award.   Here is hoping that in 2013 she wins another one for her work on HWSS.

Thank you Dr Carrie Finno for believing we did have an issue with the hooves in our Connemara ponies and then taking on our research project.

Presentation by Dr Carrie Finno on HWSS

On 13th October 2012 Dr Carrie Finno presented the outcome of her research on HWSS to the members of the American Connemara Pony Society at their Annual Meeting.    The presentation was well received by the audience.  For many of the participants this was the first information that they had seen with regards to the reality of  HWSS.  It is difficult when working on a project to not become submerged in the topic and remember that something which has taken up a good amount of one's own time, is often not known about in the wider community.  

A call was made at the meeting for further blood samples to be submitted for the study. One hopes that owners and breeders will rally to the call.  This has certainly been the case in Germany where the representative of this group has today dispatched samples from a further 28 ponies.  Another shipment is planned so if you and your ponies live in Germany and you would like to help to be part of the solution to the HWSS problem, contact the group and your details will be passed onto the person coordinating the shipments.

If there are any Connemara people in France or the UK who would be prepared to help by shipping blood samples we would really like you to contact the group.   France and the UK are the two largest Connemara pony breeding nations after Ireland. Both countries have tended to concentrate their breeding programmes on bloodlines that are less popular than those in other European countries.  It would be very interesting (and possibly advantageous) to be able to screen these populations also.

Dr Finno has kindly given permission for  a pdf version of her presentation to be posted on this blog.   Of course the pdf contains the slides only and thus does not have her explanations and commentary to explain some of the points made.  Dr Finno. HWSS Presentation 13th October 2012

In the presentation Dr Finno: 

• explains the signs of HWSS
• shows the feet of two ponies which were examined at UC Davis Veterinary Medical Teaching Hospital.
• Shows the cross-section of an affected hoof.  The lesions shown there are 'typical' of all HWSS cases.  It shows quite obviously that the breakdown is within the layers of the hoof wall and does not involve the white-line in any way.
• Genetic terminology, modes of inheritance and where HWSS fits in the wider scheme of things is explained.
• on the bottom of slide 23 is an ambiguous, to those not at the meeting, sounding statement.  The explanation is that there is no record of any person breeding two affected ponies together so the outcome of such a mating is not known. 
• HWSS is autosomal recessive; other autosomal recessive conditions in horses are discussed.  Dr Finno was one of the principal people responsible for finding the genetic marker for (HERDA) and getting this commercially available to breeders.  Also discussed is Glycogen Branching Enzyme Deficiency (GBED) and Overo Lethal White Syndrome (OLWS).
• Explains how genetic research is undertaken.  Slide 39, point 3 explains why more samples are needed.
• Explains what you can do to help to eliminate HWSS from the Connemara pony population with no loss of genetic variation.

Samples are still required from normal, non-HWSS affected, Connemara ponies

Several more enquiries have been received from people willing to help with the research at UC Davis by submitting blood samples from their ponies.  If everyone who has requested the submission forms, collection/shipping instructions and the import permit (for outside of the USA) send their samples, then the closer Bannasch Laboratory will be to having the numbers required to meet the testing protocols.

Samples from unaffected ponies are needed and wanted; there has been no shortage of submissions from affected ponies.

Time to step up people - ponies whose samples that are used in this research will be issued with a report at the end of the research.  The end of the research will occur well in advance of the test becoming available commercially because of legal/patenting issues.

So get in now and be ahead of the rest.  This opportunity could be especially relevant to owners of stallions standing at public stud or to owners who regularly sell their youngstock at weaning.  All this will cost you is the collection and shipping costs, and your time.

Private message the research group to obtain the paperwork required to submit samples.

As an 'aside' the group often gets queries about whether HWSS is present in other breeds.  It has always been the group's opinion that, yes this problem does occur in other minority breeds, but that it is the Connemara breed which has acknowledged that there is a problem and has stepped up to the plate to do something productive and useful about the issue.

So to the list of breeds with authoritative reports of a hoof condition which appears similar to HWSS, we now add Haflinger.

Today is the equinox - for those in the southern hemisphere this means the glory of Spring and rebirth.  For those in the northern hemisphere, the time when the day length really begins to telescope and for those in the colder climbs the onset of the challenges of  Autumn (Fall) and Winter.

Best wishes to all, whichever hemisphere in which you and your ponies may reside.

It is Official - More Samples required for HWSS Research

It is Official - 

UC Davis requires/needs more samples to continue with their research into the causes of HWSS.

Whole blood samples are required from both unaffected and affected ponies.

Submissions from affected ponies require high quality digital photographs to accompany the blood samples.  Where possible a full medical history is also desired.  A farrier's report could also be useful.

If you want your ponies to be part of this research project you need to contact UC Davis OR the Research Group to obtain the correct submission forms and the sample collection protocols.

Samples from outside of the USA will require an import permit which can be obtained from UC Davis or the group.

UC Davis have not indicated how many samples they need BUT let us, the Connemara community, show how important this issue is to the health and welfare of the breed and get as many samples as possible to UC Davis as quickly as possible.   

They need more samples to go onto the next stage of the research. Until they have enough the process will slow down dramatically.  Some of the research equipment used runs in cycles with 48 samples per cycle.  A run does not  get wasted  by loading less than the optimum number of samples; it all comes back to economies of scale.  So until there are enough samples for a 'run' all must wait.

Both UC Davis and the group look forward to having our in-boxes flooded with requests for submission documentation and import permits.

The contact details for UC Davis are on their poster Here is the link to UC Davis

Putting email addresses directly onto the blog, sadly invites the attentions of spam crawlers, so you will need to go directly to the UC Davis page to get their contact details.

Breaking News - HWSS is Official

It is Official!!

Because of the close relationship between the HWSS Research Group and the Bannasch Laboratory, UC Davis, we have been aware for sometime of the progress that has been made, and now we can share this publicly.

The very existence of HWSS and that it is of genetic orign of it has been questioned by many people throughout the Connemara Pony breeding world. Those who have not seen or personally experienced the condition are reluctant to accept that such a serious problem could be lurking within their beloved breed. Understandably the recurring call has been the need for scientific proof that this is not simply an environmental or management issue, but a genetic one. Now because of the dedication of a number of breeders and individuals throughout the world, we have that proof! UC Davis has released the following information into the public domain.

Here is the link to UC Davis

While this may only be the first official statement regarding research into HWSS, we believe that now is the time for an open acknowledgement that there is a cause for concern, but that there is a way out of the situation.

The ICCPS Annual General Meeting is coming up, as is the Technical Meeting. With so many delegates from breed societies around the world present for these, the research group group sincerely hopes that the UC Davis release on HWSS is enough scientific proof to acknowledge the condition, and start a constructive discussion on the issue.

For further research to continue, UC Davis needs the help of Connemara Pony owners and breeders worldwide. They need more samples from ponies, and the sooner they get them, the sooner we will have a test for the condition. The ICCPS are in a unique position to facilitate this. An education campaign to the daughter breed societies would rapidly add to UC Davis' collection of samples. Additionally, breed societies could vastly aid breeders and owners by coordinating the collection and shipment of blood samples to UC Davis. What a huge pro-active and positive step for the breed that would be!

The Connemara Pony community needs to start talking now about how to deal with the problem when a test is commercially available. There will be a time lag between the research phase being completed and when testing becoming commercial available, but that should not stop us from calmly, and rationally, discussing how this issue will be managed to the betterment of the breed.

We are not the only breed society to have faced such issues - both the Fell Pony breeders and the New Forest Pony Breeders have faced similar problems over the genetic issues in their respective breeds. And like the conditions in the above breeds, we do not believe that HWSS will be limited to just the Connemara Pony - this research will likely benefit horses worldwide.

We know the test is coming; let us as a cohesive community be positive and ready. Let the Connemara Pony community worldwide be ready and waiting to embrace the new technology as soon as it becomes available.

GET TALKING – KEEP POSITIVE AND EVERYONE WILL BENEFIT

The Research into HWSS – How was it Achieved??

The research into HWSS is the result of the dedication and perseverance of a few private individuals who rose to the challenge to provide the scientific evidence required to support their working hypothesis.

The research group made a tentative approach to researchers at the Bannasch Laboratory back in April 2011.  Because of the high standing worldwide that this laboratory has in the area of equine genetic research the group considered that any work performed by them would be well beyond any reproach .  

Although interested to be involved at a personal level, the researchers told us that to conduct the necessary initial GWAS required money – lots of money which the group did not have and until we could fund the study, there was little they could do to help.  However Bannasch did make the offer to the group that if samples were submitted to them they would extract the DNA and then store this for the future; an offer which was gratefully accepted.

The turning point came when Rosewood Witchcraft was taken to the Centre for Equine Health for a clinical workup. Thank you so much Darian, you had no idea what this action would precipitate. Rosewood Witchcraft's facebook page

Until 'Crafty' was 'seen in the flesh' the researchers really had no conception of just what the severity of this condition was. Photographs just DO NOT illustrate how dramatic this condition can be.

Shortly after Crafty's visit another affected pony made the journey to UC Davis.

These clinical examinations was the spur needed to get official, professional interest underway to research into the causes and origins of HWSS.

But of course 'we' still needed money – lots of money; thus this blog was created.

To all of you private individuals who rose to the occasion and donated funds to UC Davis to fund the GWAS and subsequent gene sequencing; 

THANK YOU FROM THE BOTTOM OF OUR HEARTS

it could not have happened without you.

The influx of funds to UC Davis allowed the initial GWAS to start. Because of the great start to fundraising UC Davis approached the Morris Foundation to apply for a dollar for dollar grant. This grant application was accepted and the Morris Foundation and two other sponsors are continuing to support the ongoing research.

BUT IT WAS 'YOUR' MONEY THAT STARTED THE BALL ROLLING

without the initial financial support from mainly private individuals within the worldwide Connemara Pony community the grant from the Morris Foundation would not have eventuated, nor that of the other two sponsors.

At this point the Connemara Pony Research Group would like to formally acknowledge the following organisations for their financial support of the research:

• American Connemara Pony Society
• Region 111 of the American Connemara Pony Society
• Ulster Connemara Pony Breeder's Association (previously known as Northern Ireland Connemara Pony Breeder's Association)
• Connemara.nu (an independent Swedish organisation which collected private donations on behalf, specifically for this project)

The above funds combined to approximately a  third of the total monies donated; the balance came from private individuals. Other than the official notifications received from the mentioned organisations, the research group has no information as to who made donations to the fund.

Another result of this blog is that many owners of affected ponies around the world made contact with the research group. 

One of these people was Kathy.  read her story here 

People who emailed the group were  put into direct contact with their country representative in the group. Much work has been performed by these representatives on behalf of both the pony owners and the research group. Without this input of samples from so many different countries, Bannasch could not have made progress as quickly as they have.

Blood collections and co-ordinated shipping of samples to Bannasch for DNA extraction (which each participating pony owner paid for themselves) have been made from Denmark, Germany/Austria, Canada, USA, Sweden and New Zealand.

UC Davis are now calling for further sample submissions.

NOW is the time for the 'ordinary' breeders and owners to unite and to become involved in this ground breaking research.

Contact the research group for help if you wish to be part of submitting samples in a co-ordinated response or UC Davis direct, if this should be your preferred option.