Sequence specificity in CpG mutation hotspots.
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.
Ollila
J
J
Department of Biosciences, Division of Biochemistry, University of Helsinki, Finland.
Lappalainen
I
I
Vihinen
M
M
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics; D001483:Base Sequence; D019175:DNA Methylation; D015226:Dinucleoside Phosphates / Q000235:genetics*; D005169:Factor VIII / Q000235:genetics; D016158:Genes, p53; D008040:Genetic Linkage; D006467:Hemophilia A / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010651:Phenylalanine Hydroxylase / Q000235:genetics; D010661:Phenylketonurias / Q000235:genetics; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics; D014960:X Chromosome
D000077329:Agammaglobulinaemia Tyrosine Kinase; D015226:Dinucleoside Phosphates; D005169:Factor VIII; D009838:Oligodeoxyribonucleotides; D010651:Phenylalanine Hydroxylase; D011505:Protein-Tyrosine Kinases; C015772:CpG dinucleotide