Document Detail


A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy.
MedLine Citation:
PMID:  20582309     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.
Authors:
Cord Drögemüller; Doreen Becker; Barbara Kessler; Elisabeth Kemter; Jens Tetens; Konrad Jurina; Karin Hultin Jäderlund; Annette Flagstad; Michele Perloski; Kerstin Lindblad-Toh; Kaspar Matiasek
Related Documents :
22980509 - Trpc6 gene variants in czech adult patients with focal segmental glomerulosclerosis and...
24708259 - The impact of vkorc1 -1639g>a genetic polymorphism upon warfarin dose requirement in di...
24656929 - Impact of insulin-like growth factor 2, insulin-like growth factor receptor 2, insulin ...
24269699 - Frequency analysis of hla class i alleles in iranian patients with progressive and non-...
24613099 - Malonyl-coa decarboxylase deficiency: long-term follow-up of a patient new clinical fea...
19329989 - The gars gene is rarely mutated in japanese patients with charcot-marie-tooth neuropathy.
23712319 - Inhabitual autosomal recessive form of dentin dysplasia type i in a large consanguineou...
19825999 - Novel mechanisms of trafficking defect caused by kcnq1 mutations found in long qt syndr...
15870199 - A common haplotype in the complement regulatory gene factor h (hf1/cfh) predisposes ind...
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-06-22
Journal Detail:
Title:  PloS one     Volume:  5     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2010  
Date Detail:
Created Date:  2010-06-28     Completed Date:  2010-09-01     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e11258     Citation Subset:  IM    
Affiliation:
Institute of Genetics, Vetsuisse Faculty, University of Berne, Berne, Switzerland. Cord.Droegemueller@itz.unibe.ch
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Animals
Cell Cycle Proteins / genetics*
Dog Diseases / genetics*
Dogs
Female
Gene Deletion*
Homozygote
Intracellular Signaling Peptides and Proteins / genetics*
Male
Mutation
Pedigree
Polyneuropathies / genetics,  veterinary*
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Cell Cycle Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/N-myc downstream-regulated gene 1 protein
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Structural optimization and de novo design of dengue virus entry inhibitory peptides.
Next Document:  The global burden of alveolar echinococcosis.