The BTHG Report, 2017, including the latest report on Copper Toxicosis research.
DNA Genome Sequencing.
Recent good news was the announcement by Catherine Mellersh, at the Breed Health Coordinators Symposium, that The Animal Health Trust have now completed the DNA Profile Sequencing for Bedlington Terriers. This may help in the proposed research soon to be carried out by a group which Dr. Susan Haywood has brought together, including Prof. Mike Herrtage, which will be mainly centred in Cambridge.
This research is to develop what they have found, i.e. the ABCA12 gene, a gene important in dogs which develop CT. In order to complete one part of the programme Dr. Haywood requires a few dogs with 2 deletions in COMMD1 (2:2’s), preferably dogs which have also been biopsied. This is to confirm whether or not ABCA12 is involved in CT in these dogs. (See Dr Haywood’s update below).
Copper Toxicosis in Bedlington Terriers – an update
Since copper toxicosis (CT) was recognised in Bedlington terriers in the UK and in other countries studies have been carried out to identify the mutant gene or genes responsible. Early studies identified an association with a deletion in the COMMD1 (Chr10) gene and genetic testing for this mutation has been used for screening for breeding. However significant numbers of biopsied affected Bedlington terriers which have only one or no COMMD1 deletions have been reported in the US, UK and Australia. Copper storage diseases (CT) have also been reported in other breeds notably Dalmatians, Labrador retrievers, Dobermann Pinchers and West Highland White Terriers. In none of these other breeds has the COMMD1 mutation been demonstrated to in any way identify affected dogs. Dogs which are both 1:1 and having no deletions, which never-the-less biopsied affected, proved that in some dogs at least COMMD1 was not causing them to have CT since their COMMD1s are completely normal and therefore functioning normally. Hence it was demonstrated that another gene must be involved in producing CT in these dogs.
A study in the UK was undertaken on biopsied affected Bedlington terriers which have one or both COMMD1 genes which do not have the mutation currently DNA tested for. This study identified a highly significant link to identifying CT status on Chr 37 containing variant SNPs on the ABCA12 gene9. This gene encodes for ABCA12, a metal binding protein bearing a close functional relationship to ATP7B responsible for Wilsons disease in humans. Put more simply the gene ABCA12 has a known role in Copper metabolism which is very similar to the role of the gene which has been found to cause Wilson’s Disease (CT) in humans. COMMD1 on the other hand does not have any direct role in Copper metabolism. Concurrently a study in Labrador retrievers has identified a mutant variant of ATP7B (Chr22) the Wilson disease copper transporter gene in their affected dogs while COMMD1 does not appear to be involved in affected dogs in this and other breeds.
In an effort to clarify what appears to be a confusing situation Liverpool (Dr Susan Haywood, Prof Stuart Carter), and Cambridge (Dr Penny Watson, Prof. Mike Herrtage) veterinary schools have joined forces to try to obtain funding from the Kennel Club to study submitted tissue (blood, liver) from Bedlington terriers affected with copper toxicosis with respect to their DNA profiles COMMD1, ABCA12 and ATP7B. We hope to include other affected dogs from target breeds in the survey.
In the meantime, we have become aware that more non-COMMD1 (i.e. dogs which are 1:1 with no copies of the COMMD1 deletion mutations or 1:2 with only one copy of the COMMD1 deletion) Bedlington terriers in the UK are being reported by their vets or breed societies with clear symptoms indicating CT. Some have already been conclusively shown to have CT and we are currently testing the most recently reported of these individuals for the ABCA12 gene. It may be the case that the original cohort of Bedlington terriers with the COMMD1 deletion have been largely removed from the population to be replaced by non- COMMD1 dogs which may be at risk of contracting copper toxicosis.
Should you have a Bedlington terrier whose DNA tests suggest it should not have CT yet it has been diagnosed as in fact having CT we ask your vet to get in touch with Dr Susan Haywood through the breed society or directly with Dr Penny Watson and /or Dr June Swinburne. We shall use the funds made available to us by the BT society to test suspected individuals for COMMD1, ABCA12 and ATP7B. There will be no extra charge. Cambridge vet school will also be available to perform liver biopsy on suspected cases but will have to charge for this at the moment.
Dr Susan Haywood
Dr Penny Watson: firstname.lastname@example.org
Dr June Swinburne: email@example.com
KC Breed Health Coordinator, BTHG Secretary, Pam Morton: firstname.lastname@example.org.
Following on from last year’s donation to Dr Haywood of £3.000 for a specialised microscope, the BTHG have donated a further £3,500 to help with the cost of the above research.