Progress Report of Study into PRA in Miniature Longhaired Dachshunds

Work carried out so far


We have identified several genetic markers that are linked to PRA in MLHDs. This means these markers are located close on the same chromosome as the gene which causes PRA. In the last year we have identified additional linked markers and established their position in relation to the PRA gene. We believe we have identified at least one marker on each side of the disease gene, which is an useful prerequisite to the development of a robust linkage-based diagnostic test.

Work currently being carried out.


Now we know the approximate location of the PRA gene we need to establish which human chromosome is equivalent (or syntenic). There is gross conservation between large sections of human and canine chromosomes, with genes that are located together on particular human chromosomes often being located together on 'homologous' canine chromosomes. But there isn't usually conservation over entire chromosomes, so any given canine chromosome will contain genes found on several different human chromosomes, albeit arranged in blocks that are each homologous to a piece of an individual human chromosome. It is as if the human chromosomes had each been cut into about four chunks; the chunks from the entire human genome have been mixed together and stuck back together in random order to generate the canine chromosomes. Once we have identified the equivalent human chromosome we can begin to look for genes that might be involved in causing PRA (so called 'candidate' genes). We use the human chromosomes as reference because vastly more work has been done with human than canine chromosomes so much more is known about them. We know which human chromosomes are homologous to the canine cliromosome on which the PRA gene is located. Unfortunately the PRA region is close to the boundary between two different human chromosomal segments, and it has been difficult to establish on which side of the boundary (i.e. on which human chromosome) the PRA gene lies. However, experiments that were carried out over the summer have been very successful and we hope to identify the equivalent human chromosome by the end of this year.

Development of a Diagnostic Test


The most reliable type of diagnostic test is a 'gene-based' test. This is a test that looks at the exact sequence of the disease-causing gene in the dog being tested, to establish whether the dog carries no, one or two copies of the disease-causing mutation (and hence whether it is clear, a carrier or affected). This type of test is 100% reliable but requires knowledge of the exact gene and mutation that cause the disease.

Before the disease gene has been identified it is possible to develop 'linkage-based' diagnostic tests based on markers genetically linked to the disease, rather than on the gene itself; these tests are less than 100% reliable but usually have a high level of accuracy (about 95-99%).
As explained above we have identified several genetic markers that, are linked to the gerie that causes PRA in Miniature LongHaired Dachshunds that could potentially be used to develop a diagnostic test. However, we have only examined these markers in a single, inbred pedigree of dogs. In order to investigate their potential use as diagnostic markers for PRA we would need to analyse the markers in dogs that are unrelated to the dogs used in our initial research and that are known to be affected with PRA. We would also need samples from unaffected close relatives. Once we have access to such samples we can investigate the potential use of the linked markers in a linkage-based diagnostic test.