title: New amino acid polymorphism, Ala/Val4058, in exon 45 of the polycystic kidney disease 1 gene: evolution of alleles.
abstract: The PKD1 gene, which is responsible for the most common form of autosomal dominant polycystic kidney disease, has recently been cloned and sequenced. Many disease-causing mutations have been characterized in this gene, most of them resulting in premature protein termination. However, mutation analysis not routinely implemented for family investigations in a clinical setting, because of the large size and complexity of the gene. Instead, genetic linkage analysis using highly polymorphic CA dinucleotide repeats that map around the gene is still the method of choice. Recently, a few intragenic polymorphisms have been described that are also useful for linkage studies. Here, a new diallelic polymorphism is described for amino acid residue 4058, Ala/Val4058, with allelic frequencies of 0.88 and 0.12, respectively, and a heterozygosity of 0.23, in the Greek and Greek-Cypriot populations. Interestingly, this polymorphism and Ala4091-A/G, which has previously been described in Caucasians, were not detected in DNA from 44 Japanese samples tested. This is particularly important when allelic frequencies in a particular population are used for linkage analysis of families of different ethnic origin. Also, observation of the two polymorphisms together as haplotypes suggests that the Ala/Val4058 polymorphism occurred more recently than the establishment of the Ala4091-A/G polymorphism, and specifically on the G allele.
authors.affiliation: Cyprus Institute of Neurology and Genetics, Department of Molecular Genetics, Nicosia, Cyprus.
authors.forename: R
authors.initials: R
authors.lastname: Constantinides
authors.forename: S
authors.initials: S
authors.lastname: Xenophontos
authors.forename: P
authors.initials: P
authors.lastname: Neophytou
authors.forename: S
authors.initials: S
authors.lastname: Nomura
authors.forename: A
authors.initials: A
authors.lastname: Pierides
authors.forename: C C
authors.initials: CC
authors.lastname: Deltas
mesh_terms: D000409:Alanine; D000483:Alleles; D000595:Amino Acid Sequence; D001483:Base Sequence; D003535:Cyprus; D017931:DNA Primers; D019143:Evolution, Molecular; D005091:Exons; D005787:Gene Frequency; D006115:Greece; D006239:Haplotypes / Q000235:genetics; D016891:Polycystic Kidney, Autosomal Dominant / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011506:Proteins / Q000235:genetics*; D050396:TRPP Cation Channels; D014633:Valine
chemical_list: D000409:Alanine; D017931:DNA Primers; D011506:Proteins; D050396:TRPP Cation Channels; D014633:Valine