title: CpG dinucleotides are "hotspots" for mutation in the antithrombin III gene. Twelve variants identified using the polymerase chain reaction.
abstract: CpG dinucleotides have been implicated as mutational hotspots in genes that are subject to control mechanisms involving methylation. We have used the polymerase chain reaction to amplify exons 2 and 6 of the human antithrombin III gene and direct sequencing to identify the base replacement in 12 genetic variants. These occurred in individuals with a history of thromboembolic disease due to functional abnormalities of circulating antithrombin: ten had decreased heparin binding and activation, two had decreased inhibitory activity. The amino acid abnormality in ten out of 12 cases had arisen at a CpG dinucleotide; this confirms the CpG sequence as a "hotspot" in the antithrombin gene and explains the observed frequency of occurrence of the same variant antithrombins in diverse populations.
authors.affiliation: Department of Haematology, University of Cambridge, U.K.
authors.forename: D J
authors.initials: DJ
authors.lastname: Perry
authors.forename: R W
authors.initials: RW
authors.lastname: Carrell
mesh_terms: D000990:Antithrombin III / Q000235:genetics*; D020152:Antithrombin III Deficiency; D001482:Base Composition; D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis; D006493:Heparin / Q000493:pharmacokinetics; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction
chemical_list: D000990:Antithrombin III; D006493:Heparin; D004247:DNA