PRA-rcd2

The test is intended for long-haired and short-haired Collies.

The higher price of the test is due to very short shelf time of chemicals needed for the analysis. If 10 samples are tested at one time, the test price is 50 EUR.

PRA-rcd2 (rod-cone dysplasia) is one of the forms of Progressive Retinal Atrophy (PRA) with very early onset of the disease. By phenotype, the disease is similar to retinitis pigmentosa (RP) in humans. Some forms of PRA are common to several races.  This specific form of PRA-rcd2 affects collies (long-haired and short-haired). In Border Collies, there is assumed existence of a gene responsible for X-bound form of PRA, so-called XLPRA3, for which the molecular genetic basis is not know at this time (Vilboux et al. 2008).

If the dog is affected by rcd2 disease, abnormal development (dysplasia) of rods and cones (photoreceptors) occurs. The development of photoreceptors is stopped and is followed by their fast degeneration. Both types of photoreceptors degenerate, while the rod degeneration is much faster than the cone degeneration and therefore, the night blindness occurs as first.   Dysplasia results in night blindness by 6-week-old puppies. In affected puppies, the rod and cone cells gradually lose their normal function in outer segments of the affected retina (Santos-Anderson et al. 1980); by 2 to 2.5 months, no photoreceptors at the outer part of the affected retina can be found.

Retinal dysfunction can be detected by means of electroretinography (ERG) in puppies by 16th day after the birth.  Ophthalmologic abnormalities can be revealed at the age of 3 to 4 months, changes in the granularity of tapetal fundus and subsequent attenuation of retinal blood vessels can be observed. Dogs affected by rcd2 are blind by the end of the first year (approximately by 6 to 8 months).

In connection with rcd2 disease, there has been found an insertion 22 bp of exon 4 of RD3-gene, localised on 7^th chromosome, in dogs (Kukekova et al. 2009). The insertion is predicted to alter the last 60 codons of one of three truncated variants of RD3-gene and further extend the reading frame in comparison with the healthy animal. The function of RD3-gene has not been fully understood so far.  The canine RD3-gene has several characteristic features, which differ from the corresponding gene in humans and mice.  Not only exist other exons and truncated variants in dogs, but the extremely GC-rich exon 4 (corresponds to exon 3 in humans and mice) also represents a problem for cloning and sequencing (Kukekova et al. 2009).

The mutation C319T has been identified in exon 3 of  RD3-gene in mice; as it creates a premature stop codon, it is considered as casual mutation for rd3 (retinal degeneration type 3) of mouse phenotype (Friedman et al. 2006). The mouse exon 3 is an orthologous gene (orthologous genes - homologous genes occurring in various species) of canine exon 4 that has mutated in case of rcd2 disease. In humans, mutations of RD3-genes, for example, of exon 2 have been identified - in case of retinopathy called Leber´s congenital amaurosis, a donor splice side has been created (Friedman et al. 2006).

RCD2 is autosomal recessive inherited disease. That means the disease affects dogs with P/P (positive / positive) genotype only. The dogs with P/N (positive / negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers).

References:

Thierry Vilboux, Gilles Chaudie et. al.: Progressive Retinal Atrophy in Border Collie: A new XLPRA (BMC Vet Res. 2008 Mar 3;4:10)

Kukekova A. V., Golstein O., Johnson J. L., Richardson M. A., Pearce-Kelling S. E., Swaroop A., Friedman J. S., Aguirre G. D., Acland G. M.: Canine RD3 mutation establishes rod-cone dysplasia type 2 (rcd2) as ortholog of human and murine rd3. Mamm Genome. 2009 Feb;20(2):109-23

Friedman JS, Chang B, Kannabiran C, Chakarova C, Singh HP et al (2006) Premature truncation of a novel protein, RD3, exhibiting subnuclear localization is associated with retinal degeneration.Am J Hum Genet 79:1059-1070