28th February 2002

Dear Jane,

A number of breeders and owners of Lhasa Apsos have been involved in the PRA research we are carrying out here in Cambridge. They have contributed with their interest, blood samples from key individuals, and with pedigree information.

I want to take the opportunity to thank all of you who are involved in this project, as well as to inform you of the state of the research.

We have been working with the candidate-gene approach in order to identify the mutation underlying PRA in Lhasa Apsos. What this means is that there are a number of genes causing retinitis pigmentosa (RP) in humans, which is equivalent to PRA in dogs, and we have been studying the state of these genes in PRA affected Lhasa Apsos. We have been particularly interested in genes in the phototransduction cascade, which is the chain of reactions that convert light into electrical impulses, and that takes place in the retina.

So far, we have studied most of the canine genes involved in the phototransduction cascade. The genes, and the results, are as follows:
cCNCG1 - not involved in the disease
RHO - not involved in the disease
ROM1 - not involved in the disease
PDE6B - uninformative (it is mutated in PRA affected Irish setters and Sloughis)
PDEG - uninformative
Phosducin - uninformative
RDS/ peripherin - uninformative
Transducin gamma - uninformative

In this case, uninformative means that no variants of the gene have been found in Lhasa Apsos. That is, all of them appear to have the same sequence for these genes. The approach used for locating the gene causing the disease requires the presence of at least two alleles in order to establish that the gene is, or is not, involved in the disease.

There are still a few genes in the phototransduction cascade that remain to be studied. In parallel to these experiments, we are trying to mount a whole-genome scan. This means that small regions throughout the entire canine genome will have to be analysed in order to see if any one of them is inherited with the disease. A large portion of these small regions will, inevitably, prove to be uninformative, since this arises from inbreeding. However, in the end, this will mean that the locus causing the disease will be mapped to a fairly large region of the genome.

Best regards,

Jesús Aguirre-Hernández