Document Detail

Glomerulopathy and mutations in NPHS1 and KIRREL2 in soft-coated Wheaten Terrier dogs.
MedLine Citation:
PMID:  23325127     Owner:  NLM     Status:  MEDLINE    
Dogs of the soft-coated wheaten terrier breed (SCWT) are predisposed to adult-onset, genetically complex, protein-losing nephropathy (average onset age = 6.3 ± 2.0 years). A genome-wide association study using 62 dogs revealed a chromosomal region containing three statistically significant SNPs (p(raw) ≤ 4.13 × 10(-8); p(genome) ≤ 0.005) when comparing DNA samples from affected and geriatric (≥14 years) unaffected SCWTs. Sequencing of candidate genes in the region revealed single nucleotide changes in each of two closely linked genes, NPHS1 and KIRREL2, which encode the slit diaphragm proteins nephrin and Neph3/filtrin, respectively. In humans, mutations in nephrin and decreased expression of Neph3 are associated with podocytopathy and protein-losing nephropathy. The base substitutions change a glycine to arginine in the fibronectin type 3 domain of nephrin and a proline to arginine in a conserved proline-rich region in Neph3. These novel mutations are not described in other species, nor were they found in 550 dogs of 105 other breeds, except in 3 dogs, including an affected Airedale terrier, homozygous for both substitutions. Risk for nephropathy is highest in dogs homozygous for the mutations (OR = 9.06; 95 % CI = 4.24-19.35). This is the first molecular characterization of an inherited podocytopathy in dogs and may serve as a model for continued studies of complex genetic and environmental interactions in glomerular disease.
Meryl P Littman; Claire A Wiley; Michael G Raducha; Paula S Henthorn
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-01-17
Journal Detail:
Title:  Mammalian genome : official journal of the International Mammalian Genome Society     Volume:  24     ISSN:  1432-1777     ISO Abbreviation:  Mamm. Genome     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-04-16     Completed Date:  2013-10-31     Revised Date:  2014-04-08    
Medline Journal Info:
Nlm Unique ID:  9100916     Medline TA:  Mamm Genome     Country:  United States    
Other Details:
Languages:  eng     Pagination:  119-26     Citation Subset:  IM    
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MeSH Terms
Amino Acid Sequence
Chromosomes / genetics
Dog Diseases / genetics*
Dogs / genetics*
Genome-Wide Association Study
Kidney Diseases / genetics,  veterinary*
Membrane Proteins / genetics*,  metabolism
Molecular Sequence Data
Sequence Analysis, DNA
Reg. No./Substance:
0/Membrane Proteins; 0/nephrin

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

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