Testing of dogs: XL-PRA

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Progressive retinal atrophy XL-PRA form in Siberian Husky and Samoyed

XL-PRA belongs to group of progressive retinal atrophy diseases. XL means X-linked, that means linked to X chromosome (female chromosome).

At the beginning, affected individuals have normal retina. The first clinical symptoms appear by ERG examination in 6 months. Later, rods light receptors begin to appear irregularly damaged. Cones damage arises in final stage of XL-PRA disease. In age of 4 years, affected dogs are usually completely blind (Zeiss et al., 2002).

There are two types of XL-PRA:

  1. XL-PRA1 in Siberian Husky and Samoyed
  2. XL-PRA2 in Miniature Schnauzer

Genomia laboratory performs testing of XL-PRA1 in Siberian Husky and Samoyed.

Inheritance of X-linked disease:

Females have XX chromosomes. So females have three possibilities as regards XL-PRA disease:

  • XnXn - females with two normal X chromosomes = normal phenotype, a healthy female
  • XnXm - females with one normal X (Xn) and one mutant X (Xm) = a female carrier. Clinical disability of female carriers is individual, depending on the X chromosome inactivation. It means that a gene expression on the X chromosome is different in different cells. Usually, female carriers are without any disability. Nevertheless, the degree of disability can be from mild to very serious.
  • XmXm - females with two mutated X chromosomes = an affected female

Males have XY chromosomes. So they have two possibilities as regards XL-PRA disease:

  • XnY - normal phenotype, a healthy male
  • XmY - an affected male; he inherited mutated X chromosome from his mother

Note:  Males are never X-linked disease carriers!

By mating healthy male and carrier female, following offspring could be expected:

Parents

Female Xn/Xm

Male  Xn/Y

Offspring

Female Xn/Xn

Female Xm/Xn

Male  Xn/Y

Male  Xm/Y

General offspring distribution

25% healthy females

25% female carriers

25% healthy males

25% affected males

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As you can see in the table, by mating healthy male and carrier female, half of the male offspring will be XL-PRA affected and half of the female offspring will transfer XL-PRA to the next generations.

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Causal mutation, mutation that causes XL-PRA1 disease, is located in ORF15 exon of dog RPGR gene (Meindl et.al. 1996). RPGR gene codes retinitis pigmentosa GTP´s regulator. Causal mutation is 5 nucleotide deletion (delGAGAA) (Zhang et al. 2002). This deletion causes a premature stop codon during retinitis pigmentosa GTP´s regulator synthesis. Mutated protein is partly able to perform his function. Loss of RPGR protein functionality is not critical in early development of light cells. But the light cells are not long-term viable (Zeiss et al. 2002).

The only reliable prevention of XL-PRA1 disease is based on breeding selection - do not use carrier females for mating!

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References:

Qi Zhang, Gregory M.Acland, Wen X.Wu, Jennifer L.Johnso, Sue Pearce-Kelling, Brian Tulloch, Raf Vervoort, Alan F.Wright and Gustavo D.Aguirre: Different RPGR exon ORF15 mutations in Canids provide insights into photoreceptor cell degeneration; Human Molecular Genetics, 2002, Vol. 11, No. 9 993-1003

Meindl, A., Dry, K., Herrmann, K., Manson, F., Ciccodicola, A., Edgar, A., Carvalho, M.R.S., Achatz, H., Hellebrand, H., Lennon, A. et al. (1996) A gene (RPGR) with homology to the RCC1 guanine nucleotide exchange factor is mutated in X-linked retinitis pigmentosa (RP3). Nature Genet., 13, 35-42.

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Usual turnaround time: 7 business days
1 test price: 54.00 $ without VAT