Dachshund Gene Gives Clue To An Inherited Human Blindness

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Main Category: Eye Health / Blindness
Also Included In: Veterinary;  Genetics
Article Date: 08 Aug 2008 - 3:00 PDT

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Scientists have discovered that a mutation in a dachshund gene called NPHP4 is involved in early onset cone rod dystrophy, a type of retinal degenerative disorder that occurs naturally in humans and dogs and eventually leads to blindness.

The study is the work of Dr Frode Lingaas of the Norwegian School of Veterinary Science and other colleagues in Norway, Sweden and the US and is published in the 7th August online before print issue of Genome Research.

Cone-rod dystrophy (CRD) is an umbrella term for a range of diseases where cone rods, the photoreceptor cells in the retina that are responsible for seeing colours and central vision, gradually degenerate. Cone rods also help us see in bright light, and their gradual loss causes dayblindness, which can eventually become total blindness.

In this study, Lingaas and colleagues found a new gene variant for early-onset cone-rod dystrophy in the wire-haired dachshund.

Previous research had already revealed a number of genes involved in inherited cases of human CRD, but the disorder has a complex genetic basis, and scientists expect more genes are waiting to be discovered.

Dogs suffer from a wide range of inherited eye disorders although only a few breeds have inherited CRD. Previous studies had already found one gene mutation for CRD in the miniature long-haired dachshund, but another genetic CRD factor common to this breed and the pit bull terrier was still unknown.

For this study, Lingaas and colleagues mapped and compared the genomes of 13 sibling pairs of wire-haired dachshunds, where one of each pair had CRD and the other did not. They isolated a region on chromosome 5 associated with CRD and found that a more detailed search of this area showed that a piece of the nephronophthisis 4 (NPHP4) gene had been deleted in affected dogs, and concluded that this deletion was most likely responsible for recessively inherited CRD in the standard wire-haired dachshund.

The researchers said the finding was interesting because the human version of NPHP4 had already been linked to disease:

"This gene has been associated with a combination of kidney and eye disease in human patients," said Lingaas.

"Here, we found a mutation that affects only the eyes, suggesting that this gene might be a candidate for human patients with eye disease only," he explained.

Speculating on how the NPHP4 variant leads to CRD only, the researchers suggested it could be that a protein coded by the mutant form of the gene may be missing a section that would normally interact with other proteins involved in eye function, but the section involved in kidney function is not missing.

Identifying genetic causes of disease may be useful in dog breeding where genetic tests can be used to breed out disorders.

Lingaas and colleagues urged that further studies were now needed to explore the underlying mechanism through which the NPHP4 deletion leads to CRD and to develop potential therapies.

"A deletion in nephronophthisis 4 (NPHP4) is associated with recessive cone-rod dystrophy in standard wire-haired dachshund".
Anne Caroline Wiik, Claire Wade, Tara Biagi, Ernst-Otto Ropstad, Ellen Bjerkås, Kerstin Lindblad-Toh, and Frode Lingaas.
Genome Research, published online before print August 7, 2008.
DOI:10.1101/gr.074302.107.

Click here for Abstract.

Sources: Journal abstract, Cold Spring Harbor Laboratory Press .

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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