title: Genomic structure of the gene for the human P1 protein (MCM3) and its exclusion as a candidate for autosomal recessive polycystic kidney disease.
abstract: The locus PKHD1 (polycystic kidney and hepatic disease 1) has been linked to all typical forms of the autosomal recessive polycystic kidney disease (ARPKD) and maps to chromosome 6p21.1-p12. We previously defined its genetic interval by the flanking markers D6S1714 and D6S1024. In our current work, we have fine-mapped the gene for the human P1 protein (MCM3), thought to be involved in the DNA replication process, to this critical region. We have also established its genomic structure. Mutation analyses using SSCP were performed in ARPKD patients' cDNA samples, leading to the exclusion of this gene as a candidate for this disorder. We also identified two intragenic polymorphisms that allowed families with critical recombination events to be evaluated. Although neither marker was informative in these individuals, they are the closest yet described for PKHD1 and may help to refine the candidate region.
authors.affiliation: Institute for Human Genetics, University of Bonn, Germany.
authors.forename: Y
authors.initials: Y
authors.lastname: Hofmann
authors.forename: J
authors.initials: J
authors.lastname: Becker
authors.forename: F
authors.initials: F
authors.lastname: Wright
authors.forename: E D
authors.initials: ED
authors.lastname: Avner
authors.forename: M
authors.initials: M
authors.lastname: Mrug
authors.forename: L M
authors.initials: LM
authors.lastname: Guay-Woodford
authors.forename: S
authors.initials: S
authors.lastname: Somlo
authors.forename: K
authors.initials: K
authors.lastname: Zerres
authors.forename: G G
authors.initials: GG
authors.lastname: Germino
authors.forename: L F
authors.initials: LF
authors.lastname: Onuchic
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002896:Chromosomes, Human, Pair 6; D004268:DNA-Binding Proteins; D005091:Exons; D015894:Genome, Human; D006801:Humans; D007438:Introns; D064126:Minichromosome Maintenance Complex Component 3; D009687:Nuclear Proteins / Q000235:genetics*; D017044:Polycystic Kidney, Autosomal Recessive / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D014157:Transcription Factors
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C066470:MCM3 protein, human; D009687:Nuclear Proteins; D014157:Transcription Factors; D064126:Minichromosome Maintenance Complex Component 3