title: Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation.
abstract: Adenine phosphoribosyltransferase (APRT) deficiency causing 2,8-dihydroxyadenine urolithiasis and renal failure is present at a high frequency among the Japanese but not other ethnic groups. A special type of mutant allele, designated APRT*J, with a nucleotide substitution at codon 136 from ATG (Met) to ACG (Thr) is carried by approximately 79% of all Japanese 2,8-dihydroxyadenine urolithiasis patients. We analyzed mutant alleles of 39 APRT deficient patients using a specific oligonucleotide hybridization method after in vitro amplification of a part of the genomic APRT sequence. We found that 24 had only APRT*J alleles. Determination of the haplotypes of 194 APRT alleles from control Japanese subjects and of the 48 different APRT*J alleles indicated that normal alleles occur in four major haplotypes, whereas all APRT*J alleles occur in only two. These results suggest that all APRT*J alleles have a single origin and that this mutant sequence has been maintained for a long period, as calculated from the frequency of the recombinant alleles.
authors.affiliation: Institute of Rheumatology, Tokyo Women's Medical College, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Kamatani
authors.forename: S
authors.initials: S
authors.lastname: Kuroshima
authors.forename: M
authors.initials: M
authors.lastname: Hakoda
authors.forename: T D
authors.initials: TD
authors.lastname: Palella
authors.forename: Y
authors.initials: Y
authors.lastname: Hidaka
mesh_terms: D000228:Adenine Phosphoribosyltransferase / Q000235:genetics*; D015139:Blotting, Southern; D003434:Crossing Over, Genetic; D008040:Genetic Linkage; D006801:Humans; D007674:Kidney Diseases / Q000235:genetics; D009154:Mutation; D015345:Oligonucleotide Probes; D015183:Restriction Mapping; D014545:Urinary Calculi / Q000235:genetics
chemical_list: D015345:Oligonucleotide Probes; D000228:Adenine Phosphoribosyltransferase