Genetic and Diagnostic Characterization of
Day Blindness in Alaskan Malamute Dogs
Dr Ian Hughes, University of Queensland
Currrent State of Knowledge:
Day blindness or hemeralopia in Alaskan Malamutes is an autosomal
recessive disease that, while vision appears normal in dim light,
results in complete blindness when in bright light (Rubin 1971).
Day blindness is now recognized as a major problem in Alaskan
Malamutes in Australia. The disease is most easily identified in
young dogs as they will walk into things and generally seem blind
when in bright light. Older dogs learn to adapt, avoiding bright
light and becoming familiar with the obstacles in their immediate
environment. The cause of the disease is a degeneration of a
particular type of photoreceptor cell in the retina of the eye
called cone cells (Aguirre and Rubin, 1974). The retina consists
of two types of photoreceptor cells, the cone cells and the rod
cells, that convert light energy into electrical energy. This
electrical energy is then sent via the optic nerve to the brain
where it is interpreted as a visual image. The rod cells operate
in dim light but cease functioning in bright light. The cone
cells work best in bright light. Thus, in the absence of cone
cells, dogs can see in dim light but are totally blind in bright
light.
The definitive diagnosis of day blindness, or cone degeneration,
is to perform an electroretinogram (ERG) which records the
electrical activity of the eye following a stimulus consisting of
a flash, or series of flashes, of light. By controlling the
intensity of the flashes and the time interval between each flash
we can measure the response of the cone cells in isolation and
thus determine if they are functioning correctly or, in the case
of day blindness, not at all. Recently a group of Australian and
overseas researchers have developed a standardized ERG protocol
for the diagnosis of day blindness (Stanley et al., 1998).
The causative gene for day blindness has not been identified.
However, in a colony of experimental dogs derived from Malamutes
in the U.S. it has been shown that the gene is located on
"linkage group" (chromosome) eight and marker genes
linked to the causative gene have been identified (Acland, Pers.
Comm.).
There are, possibly, some differences between the disease as it
is observed in our Australian Malamutes, and that in the U.S.
colony. The U.S. dogs develop photophobia (squint in bright
light) and signs of day blindness between eight and 12 weeks of
age. In Australia, photophobia has not been a notable observation
and the time of onset has appeared to be much more variable with
some reports of dogs not becoming day blind until 6 months or a
year old.
Aims and Scientific Method
for 1999:
Perform ERGs on approximately 5 more dogs using the new protocol
to confirm or rule out day blindness. This will add to a group of
19 dogs that have already been ERGd, 10 of which have been
confirmed as day blind.
Take blood samples and extract DNA from all dogs that are ERGd.
This will increase the total number of blood samples to over 40.
These samples will be used in the linkage analyses described
below.
Quantitatively analyze the ERGs to identify any differences
between carrier and normal Malamutes and between normal malamutes
and normal dogs of other breeds. It would be very useful to be
able to identify carrier animals by ERG.
Perform two linkage analyses. One in collaboration with Dr Elaine
Ostrander of the Fred Hutchinson Cancer Research Centre, Seattle,
in the U.S. and a second in our own laboratory. The first
analysis will use a homozygosity testing approach (affected dogs
are expected to be homozygous for the marker genes) and the
second will be a more traditional linkage analysis. In both cases
five different chromosome 8 markers (microsatellites) are to be
used. The aim in both cases is to confirm that the disease in
Australia and the U.S. is caused by the same gene and secondly to
identify markers that may be useful diagnostically.
Significance:
This research should provide a means, by the identification of
marker genes and/or quantitative analysis of the ERG, to
discriminate between normal and carrier dogs thus allowing for
the controlled elimination of this significant problem from the
Malamute population in Australia. We will also be able to
determine the clinical and genetic differences, if any, between
the Australian and U.S. forms of the disease.
Of broader significance is that this will be the first linkage
analysis performed in this laboratory. Once this first linkage
analysis has been done the infrastructure and experience gained
can be applied easily to all other genetic diseases of other
breeds of dog.
Results Update:
To date, the techniques for detection of variation in
microsatellite markers have been optimised and applied to three
of the five markers under investigation. Unfortunately, however,
for each of these markers the Malamute population screened
appears to be identical. That is, we are not able to use any
variation in the markers to follow the segregation of the
causative gene for day blindness. There are still two markers to
investigate. Preliminary work, with one at least, suggests that
we may be more lucky this time.
References
Aguirre, G.D., and Rubin, L.F. (1974). Pathology of hemeralopia
in the Alaskan Malamute dog. Invest. Ophthalmol. 13:231-235.
Rubin, L.F. (1971). Clinical features of hemeralopia in the adult
Alaskan Malamute. JAVMA. 158:1696-1701.
Stanley, R.G., Acland, G.M., Vingrys, A., Hardman, C., Turner,
A., Smith, R.E.I., and Hughes, I. (1998). Cone degeneration in
Alaskan Malamutes: Clinical and electroretinographic findings.
Abstract: ACVO conference, Sydney.
