Normal Japanese individuals harbor polymorphisms in the p14 ARF /INK4 locus promoters and/or other gene introns. — Variation in nucleotide sequences in each individual

Abstract

In order to investigate variation in nucleotide sequences in normal individuals, we isolated genomic DNA from the blood of healthy Japanese individuals and sequenced promoters in the p14 ARF /INK4 (p16 INK4a and p15 INK4b ) locus genes and introns in murine double minute 2, vitamin D receptor, and presenilin 1 genes. We found nucleotide alterations in the promoters, including substitutions at positions −2610 and −1536 and deletions at positions −4489, −4488 to −4483, −2241 to −2240, and −2221 to −2218 in p14 ARF and substitutions at positions −1643 and −1270 in p15 INK4b , and we found that each individual harbored polymorphisms in the locus promoters and/or introns. Some polymorphic nucleotides were included in the same set of associatively altered nucleotides. Reporter gene analysis by using luciferase revealed that altered nucleotides, including those containing the set, changed luciferase gene activity in some cell lines. The results of this study show that multi-nucleotide sequences are altered in each normal Japanese individual.