Analysis of a deletion in the nephronophthisis 4 gene in different dog breeds

Palanová, A; Schröffelová, Daniela; Pribánová, M; Dvořáková, Věra; Stratil, A.

doi:10.1111/vop.12092

Cited by 3 publications

(2 citation statements)

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“…In the 15 unaffected Shih Tzu, 46 primitive dogs (from a publicly available evolutionary database) and 20 additional dogs of non-Shih Tzu breed, although the heterozygous state was present, none were homozygous for the nonsense. Progressive retinal atrophy is a heterogenous group of retinal disorders and the mutant allele frequency ranges between 0.0052 and 0.396 depending on the gene mutations, breed and dog's geographical location (Kukekova et al 2009;Downs et al 2011;Downs et al 2013;Downs et al 2014b;Palanova et al 2014;Koll et al 2017;Karlskov-Mortensen et al 2018;Andrade et al 2019). Moreover, the mutation in one gene can be found in many different breeds.…”

Section: Discussionmentioning

confidence: 99%

Whole genome sequencing identifies a homozygous nonsense mutation in the JPH2 gene in Shih Tzu dogs with progressive retinal atrophy

et al. 2021

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Summary Progressive retinal atrophy (PRA), common autosomal recessive disorder affecting several dog breeds including Shih Tzu, is characterized by degeneration of photoreceptors leading to blindness. To identify PRA genetic variants, three affected and 15 unaffected Shih Tzu and 20 non‐Shih Tzu were recruited. Dogs underwent ophthalmologic examination and electroretinography, revealing hallmark retina pathological changes and an abnormal electroretinography in all affected dogs but not in unaffected dogs. WGS was performed. Non‐synonymous homozygous variants were searched in coding regions of genes involved in retinal diseases/development; the criterion was that variants should only be present in affected dogs and should be absent in both unaffected and 46 genomes of dogs (from an available evolutionary database). Only one out of the 109 identified variants is predicted to harbor a high‐impact consequence, a nonsense c.452A>C (p.L151X) in the JPH2 gene. The genotype of JPH2 variant in all 38 dogs was determined with Sanger sequencing. All three affected dogs, but none of the 35 unaffected, were homozygous for the nonsense variant. JPH2 has been previously found to be expressed in several excitable cells/tissues including retina photoreceptors. Hence, JPH2 is a candidate gene for PRA in Shih Tzu.

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Section: Discussionmentioning

confidence: 99%

Whole genome sequencing identifies a homozygous nonsense mutation in the JPH2 gene in Shih Tzu dogs with progressive retinal atrophy

et al. 2021

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“…However, veterinarians and the general public should be aware at least two mutations for cone‐rod dystrophy have been identified in dachshunds and that there might be other forms of PRA that affect these dogs. An inherited, early onset cone‐rod dystrophy (crd) that affected standard and miniature WHDs was described in 2007, and a mutation in the NPHP4 gene was later found to be responsible . An autosomal recessive mode of inheritance was described, and the prevalence in miniature WHDs in the United Kingdom was reported to be 3.1% .…”

Section: Discussionmentioning

confidence: 99%

The effect of repeated eye examinations and breeding advice on the prevalence and incidence of cataracts and progressive retinal atrophy in German dachshunds over a 13‐year period

Koll

Reese

Međugorac

et al. 2016

Veterinary Ophthalmology

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Nationwide genetic testing towards eliminating Lafora disease from Miniature Wirehaired Dachshunds in the United Kingdom

Ahonen

Seath

Rusbridge

et al. 2018

Canine Genet Epidemiol

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BackgroundCanine DNA-testing has become an important tool in purebred dog breeding and many breeders use genetic testing results when planning their breeding strategies. In addition, information obtained from testing of hundreds dogs in one breed gives valuable information about the breed-wide genotype frequency of disease associated allele. Lafora disease is a late onset, recessively inherited genetic disease which is diagnosed in Miniature Wirehaired Dachshunds (MWHD). It is one of the most severe forms of canine epilepsy leading to neurodegeneration and, frequently euthanasia within a few years of diagnosis. Canine Lafora disease is caused by a dodecamer repeat expansion mutation in the NHLRC1 gene and a DNA test is available to identify homozygous dogs at risk, carriers and dogs free of the mutation.ResultsBlood samples were collected from 733 MWHDs worldwide, mostly of UK origin, for canine Lafora disease testing. Among the tested MWHD population 7.0% were homozygous for the mutation and at risk for Lafora disease. In addition, 234 dogs were heterozygous, indicating a carrier frequency of 31.9% in the tested population. Among the tested MWHDs, the mutant allele frequency was 0.2. In addition, data from the tested dogs over 6 years (2012–2017) indicated that the frequency of the homozygous and carrier dogs has decreased from 10.4% to 2.7% and 41.5% to 25.7%, respectively among MWHDs tested. As a consequence, the frequency of dogs free of the mutation has increased from 48.1% to 71.6%.ConclusionsThis study provides valuable data for the MWHD community and shows that the DNA test is a useful tool for the breeders to prevent occurrence of Lafora disease in MWHDs. DNA testing has, over 6 years, helped to decrease the frequency of carriers and dogs at risk. Additionally, the DNA test can continue to be used to slowly eradicate the disease-causing mutation in the breed. However, this should be done carefully, over time, to avoid further compromising the genetic diversity of the breed. The DNA test also provides a diagnostic tool for veterinarians if they are presented with a dog that shows clinical signs associated with canine Lafora disease.

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Analysis of a deletion in the nephronophthisis 4 gene in different dog breeds

Cited by 3 publications

References 5 publications

Whole genome sequencing identifies a homozygous nonsense mutation in the JPH2 gene in Shih Tzu dogs with progressive retinal atrophy

Whole genome sequencing identifies a homozygous nonsense mutation in the JPH2 gene in Shih Tzu dogs with progressive retinal atrophy

The effect of repeated eye examinations and breeding advice on the prevalence and incidence of cataracts and progressive retinal atrophy in German dachshunds over a 13‐year period

Nationwide genetic testing towards eliminating Lafora disease from Miniature Wirehaired Dachshunds in the United Kingdom

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