Crossovers within a short DNA sequence indicate a long evolutionary history of the APRT*J mutation

Hum Genet. 1990 Oct;85(6):600-4. doi: 10.1007/BF00193582.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine Phosphoribosyltransferase / genetics*
  • Blotting, Southern
  • Crossing Over, Genetic*
  • Genetic Linkage
  • Humans
  • Kidney Diseases / genetics
  • Mutation
  • Oligonucleotide Probes
  • Restriction Mapping
  • Urinary Calculi / genetics


  • Oligonucleotide Probes
  • Adenine Phosphoribosyltransferase