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Background
of my PRA investiagations
- Simon
Petersen-Jones -
I have studying the molecular genetics of PRA for the last 10
years. My group developed the first DNA test for PRA. This was
in the Irish setter breed. We have also identified the cause
of PRA in the Cardigan
Welsh corgi
and developed a DNA-based test for that form of PRA which has
enabled breeders to ensure that no more affected dogs are produced.
The test also allows the use of carrier dogs in breeding, thus
saving the good features from such dogs while ensuring that PRA
does not occur. Eventually this test will enable the complete
eradication of PRA from the breed.
We are currently investigating PRA in about 12 different breeds
of dog and looking and many potential candidate genes in those
breeds. We are able to offer two main different approaches to
investigate PRA in any given breed.
1. Firstly we can use a candidate gene approach. This
is where we have selected several different genes that could
potentially cause PRA and developed markers for those genes.
The markers are polymorphic in several different breeds of dog.
This enables us to see if that particular gene locus is linked
to the PRA causing locus in any given breed of dog. So when we
look at PRA in a new breed once we have sufficient DNA samples
we can go through our list of candidate gene loci and see if
any are linked to the disease in that breed.
2. Secondly we can use conventional gene mapping. In this
approach instead of just looking at our candidate gene loci we
use DNA markers spread across the entire genome (rather than
markers selected only to specific gene locations) to see which
are linked to the disease locus. This approach is much more expensive
but has the advantage over the first approach that it will eventually
find linkage to the disease locus. With the first approach if
the disease is not linked to any of your candidate gene loci
the second approach must then be used. Once linkage is established
it may be possible to use a linked marker for a diagnostic test
(although there are several potential problems with this approach).
Also it is possible to see which retinal genes are close to the
marker and then investigate those genes are candidate for causing
PRA in your breed.
PRA in Shetland Sheepdogs in Scandinavia
PRA with an age of onset between 3 and 5 years of age has been
recognized as a problem in Shetland sheepdogs in Scandinavia.
This would appear to be inherited in an autosomal recessive fashion,
this is by far the commonest mode of inheritance of PRA in the
dog. This mode of inheritance makes it difficult to eradicate
the problem from the breed. Carriers of PRA do not develop the
disease themselves but can pass the PRA gene on to their offspring.
If a dog receives the PRA gene form both parents it will develop
the disease. Carriers are often only identified (if at all) after
they have been bred several times and with the later-onset form
of PRA affected dogs have often been bred from prior to the disease
being identified. These facts make autosomal recessive PRA very
difficult to eradicate.
Development and use of a DNA-based test that can identify affected
dogs and carriers at an early age makes eradication of the disease
easy. Identification of the gene mutation and development of
a PRA test is not easy. It requires that DNA samples are collected
from several affected dogs and all of the immediate relatives
(siblings, parents, grandparents and offspring – where available).
If extended pedigrees can be built up where the disease status
of the dogs is known gene searching if feasible. These techniques
are expensive – we estimate that the second approach costs
about $30,000 per year and may take 3 years or longer. The first
approach can be performed for much less cost, which is why we
most frequently use this approach. Basically the more money and
samples available the more likely it is that the search will
be successful.
Simon Petersen-Jones
Assistant Professor, Comparative Ophthalmology
Department of Small
Animal Clinical Sciences
Michigan State University
Phone: 517 353 3278
Email: peter315@cvm.msu.edu
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