Sequence specificity in CpG mutation hotspots

FEBS Lett. 1996 Nov 4;396(2-3):119-22. doi: 10.1016/0014-5793(96)01075-7.

Abstract

CpG dinucleotides are efficiently methylated in vertebrate genomes except in the CpG islands having a high C+G content. Methylated CpGs are the single most mutated dinucleotide. Sequences surrounding disease causing CpG mutation sites were analyzed from locus-specific mutation databases. Both tetra- and heptanucleotide analyses indicated clear overall sequence preference for having pyrimidines 5' and purines 3' to the mutated 5-methylcytosine. The most mutated tetranucleotides are TCGA and TCGG, the former being also a frequent restriction and modification site. The results will help in elucidating the still controversial mutation mechanism of CpG doublets.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agammaglobulinaemia Tyrosine Kinase
  • Agammaglobulinemia / genetics
  • Base Sequence
  • DNA Methylation
  • Dinucleoside Phosphates / genetics*
  • Factor VIII / genetics
  • Genes, p53
  • Genetic Linkage
  • Hemophilia A / genetics
  • Molecular Sequence Data
  • Mutation*
  • Oligodeoxyribonucleotides / genetics
  • Phenylalanine Hydroxylase / genetics
  • Phenylketonurias / genetics
  • Point Mutation
  • Protein-Tyrosine Kinases / genetics
  • X Chromosome

Substances

  • Dinucleoside Phosphates
  • Oligodeoxyribonucleotides
  • cytidylyl-3'-5'-guanosine
  • Factor VIII
  • Phenylalanine Hydroxylase
  • Protein-Tyrosine Kinases
  • Agammaglobulinaemia Tyrosine Kinase

Associated data

  • GENBANK/L47800
  • GENBANK/X01179
  • GENBANK/X02469
  • GENBANK/X58957