Clinical signs of PRA
Normal
PRA affected
• Vison is normal from birth and depending on
the age of onset, progressively degenerates
over time
• Photoreceptor response in the retina depletes
which leads to a loss of vision
• Typically loss of night vision first followed by
loss of day vision
• An eye examination by an ophthalmologist will
show a change in the blood vessels in the
retina (vascular attenuation) and a ‘shiny glow’
of the reflective layer behind the retina (tapetal
hyperreflectivity)
Recessive Disease
• PRA has an autosomal recessive mode of inheritance
• This means that a dog has to have two copies of the defective
gene (one inherited from each parent) for it to be affected by the
disease.
• Individuals with one copy of the defective gene and one copy of
the normal gene, called carriers, show no signs of disease but can
pass the defective gene onto their offspring.
Finding a disease mutation using a
Genome Wide Association Study
(GWAS)…
• Scans markers across the genome in a set of
individuals affected with a particular disease
(cases) and individuals clear of the disease
(controls)
• Identifies a region associated with a particular
disease
AHT research - GWAS
Our study…
17 Lhasa Apso’s with PRA (cases)
27 Lhasa Apso’s >8 years free of PRA (controls)
PRA4 mutation
• A large insertion in the normal DNA sequence causes PRA in the Lhasa Apso
• This type of PRA in the breed will be termed ‘Progressive Retinal Atrophy - Type 4’ or
‘PRA4’
Normal DNA
sequence
‘Mutant’ DNA sequence
with additional DNA
inserted
DNA test developed based on this mutation –
official launch date Monday 4
th
September 2017
DNA test results
There are 3 possible DNA test results:
• AFFECTED: The dog has two copies of the PRA4 mutation and is affected
or will become affected with PRA.
• CARRIER: The dog has one copy of the normal gene and one copy of the
mutant gene that causes PRA4. It will not develop PRA but will pass on the
PRA4 gene to 50% (on average) of its offspring.
• CLEAR: The dog has two copies of the normal gene and will neither
develop PRA, nor pass a copy of the PRA4 gene to any of its offspring.
Breeding with carriers
• Although we are unsure of the frequency of the PRA4 mutation in
the Lhasa Apso breed, this will be monitored now the test is
available and updates given to the Breed Club once we have
tested more dogs.
• Our advice is to breed with carriers for the first few
generations following the development of the DNA test
• If carriers are not bred from there could be a rapid reduction of
the breed gene pool
Breeding with carriers
• Remember – the PRA4 mutation is probably NOT the only mutation a
dog is carrying
• Carriers can be safely bred with, providing they are mated to a DNA
tested dog that is CLEAR
• Any puppies that will be bred from need to be DNA tested themselves
prior to breeding
• Non-breeding pet dogs DO NOT need to be DNA tested
Priorities
1. Avoid breeding dogs that could develop PRA
• PRA is a blinding disease and now there is a DNA test there is NO excuse
for producing affected dogs
2. Reduce the frequency of the mutation within the breed
• This can be done slowly, over several generations
• Allow yourselves time to capture all the other desirable features that are
important (e.g. temperament) before restricting breeding to clear dogs only
Combination of Dogs Outcome
Possibility of puppies
with PRA?
Clear
X Clear
All puppies will be clear
No
Clear
X Carrier
~ 50
% of puppies will be clear
~ 50
% of puppies will be carriers
No
Clear
x Affected
All puppies will be carriers
No
Carrier
x Carrier
~ 25
% of puppies will be clear
~ 25
% of puppies will be affected
~ 50
% of puppies will be carriers
Yes
Carrier
x Affected
~ 50
% of puppies will be affected
~ 50
% of puppies will be carriers
Yes
Affected
x Affected
All puppies will be affected
Yes
Which dogs qualify for free
DNA test results?
Samples submitted to the research study that were either:
a) Lhasa Apso’s diagnosed with PRA by a BVA/KC/ISDS panellist (or the European equivalent) with
an examination certificate or a referral letter from a veterinary ophthalmologist
a) Lhasa Apso’s over the age of 8 years diagnosed as PRA-free by a BVA/KC/ISDS panellist (or the
European equivalent) with an examination certificate or a referral letter from a veterinary
ophthalmologist
Those eligible to receive free DNA test results will not need to purchase a test and will receive their
dog(s) results to the email address provided at sample submission, if the owner so wishes to receive
this result.
