Thursday, 6 June 2013

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 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)

(2001) an immunodeficiency in Fell ponies: a preliminary study into cellular responses.
Equine Veterinary Journal 33, 687–692
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
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
JElINEK, F., FALDYNA, M. & JASURKOVA-MIKUTOVA, G. (2006) Fell pony syndrome in a pony in North america. Journal of Veterinary Internal Medicine 20,
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
& 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, 
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:
Provenance: Not commissioned;
externally peer reviewed
Accepted February 14, 2013