The Finnish lapphund retinal atrophy locus maps to the centromeric region of CFA9

Abstract

BackgroundDogs have the second largest number of genetic diseases, after humans. Among the diseases present in dogs, progressive retinal atrophy has been reported in more than a hundred breeds. In some of them, the mutation has been identified and genetic tests have allowed the identification of carriers, thus enabling a drastic reduction in the incidence of the disease. The Finnish lapphund is a dog breed presenting late-onset progressive retinal atrophy for which the disease locus remains unknown.ResultsIn this study we mapped the progressive retinal atrophy locus in the Finnish lapphund using a DNA pooling approach, assuming that all affected dogs within the breed share the same identical-by descent-mutation as the cause of the disease (genetic homogeneity). Autosomal recessive inheritance was also assumed, after ruling out, from pedigree analysis, dominant and X-linked inheritance. DNA from 12 Finnish lapphund cases was mixed in one pool, and DNA from 12 first-degree relatives of these cases was mixed to serve as the control pool. The 2 pools were tested with 133 microsatellite markers, 3 of which showed a shift towards homozygosity in the cases. Individual genotyping with these 3 markers confirmed homozygosity for the GALK1 microsatellite only (chromosome 9). Further individual genotyping with additional samples (4 cases and 59 controls) confirmed the association between this marker and the disease locus (p < 0.001). Closely related to this breed are the Swedish lapphund and the Lapponian herder for which a small number of retinal atrophy cases have been reported. Swedish lapphund cases, but not Lapponian herder cases, had the same GALK1 microsatellite genotype as Finnish lapphund cases.ConclusionThe locus for progressive rod-cone degeneration is known to be close to the GALK1 locus, on the telomeric region of chromosome 9, where the retinal atrophy locus of the Finnish lapphund has been mapped. This suggests that the disease in this breed, as well as in the Swedish lapphund, may correspond to progressive rod-cone degeneration. This would increase the number of known dog breeds having this particular form of progressive retinal atrophy.

Genetic and phenotypic variations of inherited retinal diseases in dogs: the power of within- and across-breed studies

“…While successful mapping of many diseases has used purpose-bred research colonies, some studies benefitted from recruiting cases and controls from client-owned pet dogs. Using samples and clinical data from client-owned dogs, the chromosomal location of prcd in the American Eskimo and Finish Lapphund breeds was independently mapped by homozygosity mapping using only 13 (Moody et al 2005) and 12 (Aguirre-Hernandez et al 2007) affected cases, respectively. The use of pet dogs eliminates the difficulties and expense of developing and maintaining a research colony.…”

A slowly progressive retinopathy in the Shetland Sheepdog

“…The retinopathy in Shetland Sheepdogs does not resemble the specific retinopathies reported in other breeds of dogs, such as the Borzoi, Bernese Mountain dog, Coton de Tulear, Lapponian Herder dog (Finnish Lapphund), Great Pyrenees dog and the Swedish Vallhund (Västgötaspets) 2–8 . It has also been shown by DNA testing of three dogs affected with SPR that prcd ‐PRA and SPR are not caused by the same mutation.…”

“…To the authors’ knowledge, no further descriptions have been published on this disease. Other specific retinopathies have been reported in several breeds of dogs, such as the Bernese Mountain dog, Borzoi, Coton de Tulear, Lapponian Herder dog (Finnish Lapphund), Great Pyrenees dog and in the Swedish Vallhund (Västgötaspets) 2–8 . The clinical presentation in the examined Shetland Sheepdogs is dissimilar to the retinopathies described in the other breeds, which indicates that it is likely to be a different condition.…”

Retinal degeneration in nine Swedish Jämthund dogs

“…However, the genetic causes of different forms of PRA are still unknown in a number of breeds such as Papillon and Tibetan Spaniel. [9][10][11] The pedigree analysis is suggestive of an inherited disease, but the contribution of environmental factors (such as diet, light exposure, infectious agents) cannot be ruled out.…”