title: Characterization of allelic and nucleotide variation between the RAGE gene on chromosome 6 and a homologous pseudogene sequence to its 5' regulatory region on chromosome 3: implications for polymorphic studies in diabetes.
abstract: Activation of the receptor for advanced glycation end products (RAGE) appears to be a key mechanism in the pathogenesis of diabetic vascular disease, making RAGE a candidate gene for investigation. RAGE is located in the major histocompatibility complex locus on chromosome 6, which contains a multitude of overlapping and duplicated genes involved predominantly in inflammatory and immune responses. The RAGE 5' flanking region from -505 in a 5' direction overlaps with PBX2, a gene that has a pseudogene copy on chromosome 3, making any studies of polymorphisms in this duplicated region potentially fraught with error. In this study we have addressed these issues by confirming RAGE as a predominantly single-copy gene and PBX2 to have two gene copies in the haploid human genome. We have characterized the gene:pseudogene differences between RAGE/PBX2 on chromosome 6 and PsiPBX2 on chromosome 3, which include a change from C to A at position -1139 RAGE/+2298 PBX2, previously reported as a polymorphism. Single chromosome-specific DNA amplification of the duplicated region has clarified five polymorphisms to be on chromosome 3 and one (at -1202 RAGE/+2234 PBX2) to be on chromosome 6. In conclusion, this study provides essential data for the study of RAGE and its genetics.
authors.affiliation: Academic Unit of Molecular Vascular Medicine, University of Leeds, Leeds General Infirmary, Leeds, UK. b.hudson@leeds.ac.uk
authors.forename: B I
authors.initials: BI
authors.lastname: Hudson
authors.forename: M H
authors.initials: MH
authors.lastname: Stickland
authors.forename: P J
authors.initials: PJ
authors.lastname: Grant
authors.forename: T S
authors.initials: TS
authors.lastname: Futers
mesh_terms: D020413:3' Untranslated Regions; D000483:Alleles; D001483:Base Sequence; D002893:Chromosomes, Human, Pair 3; D002896:Chromosomes, Human, Pair 6; D004247:DNA / Q000737:chemistry*; D003920:Diabetes Mellitus / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011544:Pseudogenes; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000235:genetics*; D012045:Regulatory Sequences, Nucleic Acid; D016415:Sequence Alignment
chemical_list: D020413:3' Untranslated Regions; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D004247:DNA