title: Novel nucleotide substitutions within the coding region of DNMT2 are in strong linkage disequilibrium in Caucasians and Japanese.
abstract: Investigations into mechanims by which cytosine methylation may be genetically controlled have led to the identification of single nucleotide polymorphisms within the coding region of DNMT2 that are conserved in different ethnic groups. The DNMT2 I allele includes a G at nucleotide position 104 of exon 2 and a C at position 50 of exon 4. The alternative allele, DNMT2 II, includes an A and T, respectively, at these positions. G was never found in the absence of C and vice versa and A was never found in the absence of T and vice versa. The gene products of DNMT2 I and DNMT2 II differ by the inclusion of a histidine or tyrosine residue at the position specified by codon 101. This amino acid substitution alters the amino acid composition of a conserved methylating enzyme motif shown to be involved in S-adenosylmethionine binding in M.HhaI, a bacterial methyltransferase that is almost identical to DNMT2 in size and structure. Demonstration of strong linkage disequilibrium between the nucleotide substitutions associated with each DNMT2 allele provides valuable tools for the investigation of molecular genetic mechanisms of evolution and speciation.
authors.affiliation: Department of Pathology, The University of Western Australia, Perth, Australia.
authors.forename: M
authors.initials: M
authors.lastname: Franchina
authors.forename: P H
authors.initials: PH
authors.lastname: Kay
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D016207:Cytokines / Q000235:genetics; D004247:DNA / Q000032:analysis; D004248:DNA (Cytosine-5-)-Methyltransferases / Q000235:genetics*; D017931:DNA Primers / Q000737:chemistry; D005091:Exons; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007564:Japan / Q000208:ethnology; D015810:Linkage Disequilibrium; D008745:Methylation; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D020033:Protein Isoforms / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044465:White People / Q000235:genetics*
chemical_list: D016207:Cytokines; D017931:DNA Primers; D020033:Protein Isoforms; D004247:DNA; D004248:DNA (Cytosine-5-)-Methyltransferases; C112218:TRDMT1 protein, human