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DNA testing scheme for Irish Setters - PRA rcd4

Following consultation with the Irish Setter Breed Health Committee, the Kennel Club has recently approved a new official DNA testing scheme for PRA (rcd-4) in the breed.

Follow the link for further information:



DNA Testing for PRA RCD4 is available

We advise that all breeding stock is tested before mating. 


Following a meeting between Professor Ed Hall, Chairman of the Breed Health Committee, Dr Cathryn Mellersh. Canine Genetics Research Group Leader from AHT and Dr Jeff Sampson, Genetics consultant to the Kennel Club we have been advised by Ed Hall that in addition to the 7 dogs which have been identified with PRA rcd4 there are 3 more having "mid-onset" PRA and which do not have rcd1 or rcd4. 

Any Irish Setter with suspected sight problems can have DNA testing free-of-charge if the sample sent to the AHT is accompanied by a certificate from a veterinary ophthalmologist confirming PRA       (Progressive Retinal Atrophy).

To get your dog tested for PRA by an ophthalmologist you will need to see your vet first and ask for a referral to an eye specialist.



Joint Irish Setter Breed Clubs

Statement on the control of the rcd4 mutation in Irish Setters

The Joint Irish Setter Breed Clubs (JISBC) have drawn up the following guidelines for the control of the recently discovered rcd4 mutation which causes Late Onset Progressive Retinal Atrophy (LOPRA) in Irish Setters. Whilst it should be stressed that clinical signs of LOPRA usually appear after the age of 9 years, the JISBC still believe it to be a welfare issue, although it is noted that many dogs can cope with blindness.

Data from the Animal Health Trust so far suggest the prevalence of carriers of the rcd4 mutation (i.e. heterozygotes) in the breed is about 42% and therefore the proposed guidelines are considered appropriate at this time. The JISBC recognises the need to maintain genetic diversity within the breed and does not yet recommend a complete ban on breeding using carrier or affected dogs.

However, the principle of these guidelines is that no dogs should be produced that will develop PRA and become blind, and therefore all members of the JISBC agree that:

     1. All caring and resonsible breeders will test their stock before planning a mating.

  • Any rumour and supposition about a dog’s genetic status should be ignored; DNA-testing should be undertaken.
  • As DNA-testing is now available, ‘hereditarily clear’ dogs will be produced. However such dogs should still be tested before being used for breeding because of the potential difficulty in proving parentage.
  • If the rcd4 status of any stud dog, or its semen, is unknown then the bitch to be mated must be tested and found CLEAR.                                                                                    

2. AFFECTED dogs (i.e. homozygous for the rcd4 mutation) should never be mated with other AFFECTED dogs as all progeny will be AFFECTED.

Thus the following are recommendations about potential matings that the JISBC consider acceptable at this time:

  • CLEAR x CLEAR matings are encouraged.
  • CLEAR x CARRIER* matings: progeny will, on average, be CLEAR (50%) or CARRIERS (50%) and should be DNA‑tested before breeding.
  • CLEAR x AFFECTED* matings: all progeny will be CARRIERS.

* It is recommended that any use of AFFECTED and CARRIER stud-dogs is given serious, cautious consideration by both stud-dog owners and breeders before planning a mating.

Purchasers of any dogs produced by CLEAR x CARRIER and CLEAR x AFFECTED matings should be advised that these dogs will not develop PRA rcd-4, but should not be used for breeding unless tested.


All breeders should note that AFFECTED x CARRIER or CARRIER x CARRIER matings may produce some AFFECTED dogs.

  1. CARRIER x CARRIER matings will produce, on average, 25% AFFECTED progeny.
  2. AFFECTED x CARRIER matings will produce, on average, 50% AFFECTED progeny.

Purchasers of any dogs produced by such matings should be advised that some of these dogs may develop PRA rcd-4 and should not be used for breeding unless DNA-tested.


The JISBC will continue to monitor the prevalence of the rcd4 mutation within the breed. However it is aware that a further PRA mutation that causes blindness at an earlier age (so-called mid-onset PRA) may be present in the breed but has yet to be confirmed and characterised genetically. Thus control measures for rcd4 may need to be modified if this new form of PRA is prevalent, as the earlier onset of blindness clearly has an even greater welfare implication.


Signed on behalf of the following breed clubs, which endorse and support these recommendations

  • Belfast & District Irish Setter Club
  • The Irish Setter Association England
  • The Irish Setter Breeders Club
  • The  Irish Setter Club of Scotland
  • The  Irish Setter Club of Wales
  • The  Midlands Irish Setter Society
  • North-East of England Irish Setter Club
  • The  South of England Irish Setter Club


Professor E J Hall


Chairman, Irish Setter Breed Clubs Health Coordinator Group

29 February 2012




Statement from The Animal Health Trust   

Progressive Retinal Atrophy in the Irish Setter

Progressive Retinal Atrophy (PRA) is a well-recognised inherited condition that many breeds of dog are predisposed to.  The condition is characterised by bilateral degeneration of the retina which causes progressive vision loss that culminates in total blindness.  There is no treatment for PRA, of which several genetically distinct forms are recognised, each caused by a different mutation in a specific gene.  The various forms of PRA are typically breed-specific, with clinically affected dogs of the same breed usually sharing an identical mutation.  Clinically affected dogs of different breeds, however, usually have different mutations, although PRA-mutations can be shared by several breeds.

A mutation for an early-onset form of PRA, known as rcd1, was identified in Irish Setters as long ago as 1993, and is well-documented to affect dogs from a few weeks of age.   More recently dogs have been identified with a seemingly different form of PRA that affects dogs later in their lives and is known to be different from rcd1.  This alternative form became known as “LOPRA” – for Late-Onset PRA.  Unlike rcd1, where all dogs became affected at almost exactly the same age the age of onset of dogs with LOPRA varied, from a few years of age (2-3 yo) up to old age (10-11 yo).  It was unclear whether these dogs all shared the same form of PRA or whether there were genetically distinct forms of PRA segregating in this breed.


Mutation Identified

In 2011 geneticists working in the Kennel Club Genetics Centre at the Animal Health Trust identified a recessive mutation that is associated with the development of LOPRA in the Gordon Setter.  Owners of Gordon Setters with LOPRA report that their affected dogs develop night blindness in the first instance, which is indicative of a rod-cone degeneration, so we have termed this mutation rcd4 (for rod-cone degeneration 4) to distinguish it from other, previously described, forms of rod-cone degeneration.

Following our work with rcd4 in the Gordon Setter we have found some Irish Setters that have been diagnosed with PRA also carry two copies of the rcd4 mutation.  As a result the AHT will make the rcd4 DNA test available to Irish Setters, from August 1st 2011.  The DNA test we are offering examines the DNA from each dog being tested for the presence or absence of this precise mutation and is thus a ‘mutation-based test’ and not a ‘linkage-based test’. 


Other Forms of PRA

The research we have carried out to identify the rcd4 mutation has revealed that there are at least three forms of PRA segregating in the Irish Setter; rcd1, rcd4 and an additional, third form, that has yet to be identified.  We know there is a third form of PRA because of the ten dogs with LOPRA, whose DNA we have been sent to analyse, only 7 have two copies of the rcd4 mutation.  The remaining 3 dogs do not carry either the rcd1 or rcd4 mutations, meaning their PRA must be due to another, as yet unidentified, mutation.  There is some evidence that this third form of PRA has, on average, an earlier age of onset than rcd4, but we need to examine more dogs before we can be confirm this.

The age at which dogs with the rcd4 mutation develop PRA seems to vary and we know about dogs as young as 4yo and as old as 10yo, that have been diagnosed with LOPRA, and that carry two copies of rcd4 mutation.  But it is important to remember that the age at which a dog is diagnosed with PRA can vary according to circumstances, and is not necessarily the same age at which it started to develop PRA.  For example, a dog whose PRA is detected at a routine eye examination will have an earlier age of diagnosis than a dog whose PRA was only detected once it started to lose its sight.  It is also possible that the dogs that have developed PRA very early also carry the mutation for the third, unidentified, form of PRA (as well as rcd4) and it is this ‘mid onset’ mutation that has caused them to develop PRA at a relatively young age.  More research will be required to understand the variability in age of onset more fully.

Our research indicates rcd4 is a common form of PRA among Irish Setters and the development of this test therefore enables breeders to slowly decrease the frequency of an important form of PRA in their lines.  However, because we know that at least one other form of LOPRA exists within the breed, we cannot guarantee that any dog will not develop PRA, even if they are clear of the rcd4 mutation. 


Rcd4 DNA Test

Breeders using the rcd4 DNA test will be sent results identifying their dog as belonging to one of three categories.  In all cases the terms ‘normal’ and ‘mutation’ refer to the position in the DNA where the rcd4 mutation is located; it is not possible to learn anything about any other region of DNA from the rcd4 DNA test. 

CLEAR: these dogs have two normal copies of DNA.  Clear dogs will not develop PRA as a result of the rcd4 mutation, although we cannot exclude the possibility they might develop PRA due to other mutations they might carry that are not detected by this test.

CARRIER: these dogs have one copy of the mutation and one normal copy of DNA. These dogs will not develop PRA themselves as a result of the rcd4 but they will pass the mutation on to approximately 50% of their offspring.  We cannot exclude the possibility that carriers might develop PRA due to other mutations they might carry that are not detected by this test. 

GENETICALLY AFFECTED: these dogs have two copies of the rcd4 mutation and will almost certainly develop PRA during their lifetime.  The average age of diagnosis for dogs with rcd4 is 10 yo, although there is considerable variation within the breed.



Our research has demonstrated that the frequency of the rcd4 mutation in Irish Setters is high and approximately 30-40% of dogs might be carriers. The mutation is recessive which means that all dogs can be bred from safely but carriers and genetically affected dogs should only be bred to DNA tested, clear dogs.  About half the puppies from any litter that has a carrier parent will themselves be carriers and any dogs from such litters that will be used for breeding should themselves be DNA tested prior to breeding so appropriate mates can be selected.  All puppies that have a genetically affected parent will be carriers.

It is advisable for all breeding dogs to have their eyes clinically examined by a veterinary ophthalmologist prior to breeding and throughout their lives so that any cases of PRA caused by additional mutations can be detected and that newly emerging conditions can be identified.



PRA rcd4 (LOPRA)    Some questions answered

(please read this alongside the AHT announcement)

I have been asked a number of questions on this subject, and the following answers try to throw light on the current situation.

  1. What does it mean to be genetically affected but not yet clinically affected by PRA rcd4?

Unlike PRA rcd1 and CLAD, which can be seen in very young puppies, PRA rcd4 may not be visible to the owner or even to the vet or ophthalmologist until later in life.  The dog is genetically affected from birth and a DNA test for PRA rcd4 will show this; however the clinical signs of deteriorating eyesight will not be present until sometime later in life and, in fact in a few cases, may never occur.  The dog has the defective genes from birth although the clinical signs are not present and this must be understood when considering a breeding programme.

  1. Explain the meaning of “homozygous for PRA rcd4”.

This is frequently referred to as having “two copies of the mutant gene” and thus being genetically affected.

In layman’s terms this means that the defective gene is inherited from both parents.    

If the defective gene is inherited from only one parent the dog will be a “carrier” of the condition  which means the defective gene can be passed to the offspring but this dog will never have this condition.  This is typical of a recessive mutant gene and most of us are familiar with it in PRA rcd1 and CLAD.

  1. Remind me what happens if an affected dog is mated to a clear.

AFFECTED to CLEAR >>>>>>>>>>  100% CARRIERS


CARRIER to CLEAR >>>>>>>>>>>> 50% CARRIERS; 50% CLEAR


  1. How do we know there might be 30-40% of dogs in our breed that are carriers?

A random check was performed on a large number of DNA samples stored at the AHT and this provided the information.  The large number of samples used by the AHT means that the proportion of carriers for that sample is likely to reflect the proportion throughout our breed.

  1. Will we be told the individual results from this test run?

No.  The AHT have permission to use the samples stored for research purposes i.e. in the development of a new test, and to provide a statistical analysis of the results but not to provide individual dog’s names or results.

The way forward is to test the dogs you own now, particularly your breeding stock, and to move forward from this.

The advice so far is to avoid producing genetically affected puppies – if you find you have an affected dog or a carrier with which you wish to breed only breed to a clear dog.

  1. What do we know about another form of LOPRA that exists in the breed?

We know there is a third form of PRA in the breed as 3 dogs have been clinically identified as having PRA but their DNA shows that they do not have PRA rcd1 or PRA rcd4.  It probably occurs at a younger age then PRA rcd4.  It may be the cause of blindness in the younger dogs that also have the PRA rcd4 mutation.  Further research will be needed to find the mutation if more cases are found.  

  1. How many dogs so far (July 2011) are homozygous for PRA rcd4?

We only know of 7, 6 of which have been named by their owners.  I understand that there were very few in the research run but we have not been given further information on this.  I do, however, have a personal story to tell as a result of this research run.

My experience has been with my old dog, Willow (Kirkavagh Karamita of Follidown), until now referred to in newsletters but not named because of the uncertainty involved in her condition at the time.  During the research she was found to have two copies of (i.e. homozygous for) the PRA rcd-4 mutation and she was blind and she was 13 years old.  This seemed to confirm the research programme but on examination by two highly respected ophthalmologists she was found not to have LOPRA.  Her blindness was caused by typical problems of old age – some cataract and sclerosis of the lens.  If she had lived longer she may have developed LOPRA but, very sadly, she died in April.   ( Incidentally, she coped very well in her familiar environment with her blindness but did need extra help and consideration because of her condition.)

Most of you will have read about her already but it provides an important case study and a good reason not to panic if the DNA test shows your dog to be homozygous for PRA rcd-4.  Your dog may never go blind despite having the genetic mutation.

If you have any further questions, please email me and I will try to help.

Gillian Townsend

ISAE Health Representative.

Email: townsendatwaitrose [dot] com


 A statement from the Irish Setter Breed Clubs Health Coordinators Committee concerning

Late Onset Progressive Retinal Atrophy (LOPRA)

Recently, DNA samples from Irish setters diagnosed with Late Onset Progressive Retinal Atrophy (LOPRA) have been submitted to the Animal Health Trust for genetic analysis. So far several dogs have been diagnosed with two copies of the rcd-4 mutation (i.e. homozygous). This means these dogs are clinically affected with a condition that has previously been described in Gordon setters.

The Animal Health Trust is hoping to release a DNA test for rcd-4 in Irish setters in the near future and when it is available the scale of the problem in the breed can be assessed and an appropriate strategy to eradicate the condition can begin. Until that time the Committee advises against panic and ill‑informed rumour.

Whilst the recognition of LOPRA in the breed is a serious and unwanted development, we should take heart that previous genetic problems (e.g. PRA rcd-1, CLAD) in the breed have been conquered by dedicated breeders implementing controlled breeding schemes, and there is no reason to doubt an eradication programme, when launched, will be successful.

Professor Ed Hall

Chairman, Irish Setter Breed Clubs Health Coordinators Committee


Irish Setter Breed Clubs Health Coordinators Committee

Late Onset Progressive Retinal Atrophy (LOPRA)


Following the discovery of Irish setters clinically affected with LOPRA in association with two copies of the rcd-4 gene (i.e. homozygous), so far the following six dogs (in alphabetical order) have been identified as affected.

  • Joben Midnight Memories
  • Joben Midnight Moments
  • Konakakela Red Admiral at Ixia
  • Millcroft the Moon's Shadow
  • Starchelle Buddy Holly
  • Wickenberry Capsicum

These names are being published with the permission of their owners/breeders in a spirit of openness in order to alert responsible owners and breeders and to prevent the propagation of unfounded rumours.

We await an announcement from the Animal Health Trust on when the rcd-4 test will be made available.

Professor Ed Hall

Chairman, Irish Setter Breed Clubs Health Coordinators Committee