title: Genomic organization and mutation screening of the human ortholog of Pkdr1 associated with polycystic kidney disease in the rat.
abstract: Autosomal dominant polycystic kidney disease (ADPKD) is one of the most common inherited disorders in humans. Although disease-causing mutations have been found in two genes, PKD1 and PKD2, a small number of ADPKD families exist that are unlinked to either of these genes, suggesting involvement of a third, as yet unidentified PKD3 gene. Susceptibility to renal cyst formation in the (cy/+) rat is caused by a missense mutation in Pkdr1 encoding the novel protein SamCystin. To initiate studies of the human orthologous gene, we determined the location and the organization of human PKDR1. We genotyped microsatellite markers flanking the human ortholog in PKD families that either are unlinked to known PKD genes, or in which mutations have not yet been identified and carried out mutation analysis in PKD patients. We identified eight novel single nucleotide polymorphisms, including three leading to amino acid changes. These variants are unlikely to account for PKD in these patients, yet the screening of other affected populations may provide information about the involvement of PKDR1 as a modifier gene in cystic kidney disease.
authors.affiliation: The Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
authors.forename: Pamela J
authors.initials: PJ
authors.lastname: Kaisaki
authors.forename: Carsten
authors.initials: C
authors.lastname: Bergmann
authors.forename: Joanna H
authors.initials: JH
authors.lastname: Brown
authors.forename: Patricia
authors.initials: P
authors.lastname: Outeda
authors.forename: Xosé M
authors.initials: XM
authors.lastname: Lens
authors.forename: Dorien J M
authors.initials: DJ
authors.lastname: Peters
authors.forename: Norbert
authors.initials: N
authors.lastname: Gretz
authors.forename: Dominique
authors.initials: D
authors.lastname: Gauguier
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Bihoreau
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D000818:Animals; D015894:Genome, Human; D006801:Humans; D020125:Mutation, Missense; D009687:Nuclear Proteins / Q000737:chemistry* / Q000378:metabolism*; D017354:Point Mutation; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D051381:Rats; D050396:TRPP Cation Channels / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009687:Nuclear Proteins; D050396:TRPP Cation Channels; C532258:ANKS6 protein, human; C532259:Anks6 protein, rat