a non-synonymous mutation in the canine pkd1 gene is associated with autosomal dominant polycystic kidney disease in bull terriers犬的非同义突变pkd1基因与常染色体显性遗传多囊肾疾病有关斗牛犬.pdfVIP

A Non-Synonymous Mutation in the Canine Pkd1 Gene Is Associated with Autosomal Dominant Polycystic Kidney Disease in Bull Terriers 1 2 1 3 4 Puya Gharahkhani , Caroline A. O’Leary *, Myat Kyaw-Tanner , Richard A. Sturm , David L. Duffy 1 School of Veterinary Science, The University of Queensland, Gatton, Queensland, Australia, 2 Centre for Companion Animal Health, The University of Queensland, Brisbane, Queensland, Australia, 3 Melanogenix Group, Institute for Molecular Bioscience, The University of Queensland, Brisbane, Queensland, Australia, 4 Epidemiology Group, Queensland Institute of Medical Research, Brisbane, Queensland, Australia Abstract Polycystic Kidney Disease is an autosomal dominant disease common in some lines of Bull Terriers (BTPKD). The disease is linked to the canine orthologue of human PKD1 gene, Pkd1, located on CFA06, but no disease-associated mutation has been reported. This study sequenced genomic DNA from two Bull Terriers with BTPKD and two without the disease. A non- synonymous G.A transition mutation in exon 29 of Pkd1 was identified. A TaqManH SNP Genotyping Assay was designed and demonstrated the heterozygous detection of the mutation in 47 Bull Terriers with BTPKD, but not in 102 Bull Terriers over one year of age and without BTPKD. This missense mutation replaces a glutamic acid residue with a lysine residue in the predicted protein, Polycystin 1. This region of Polycystin 1 is highly conserved between species, and is located in the first cytoplasmic loop of the predicted protein structure, close to the PLAT domain and the second transmembrane region. Thus, this change could alter Polycystin 1 binding or localization. Analytic programs PolyPhen 2, Align GVGD and SIFT predict this