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

Autor: Peter J. Grant, M. H. Stickland, T. Simon Futers, Barry I. Hudson
Rok vydání: 2001
Předmět:
Zdroj: Diabetes. 50:2646-2651
ISSN: 1939-327X
0012-1797
DOI: 10.2337/diabetes.50.12.2646
Popis: 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 ΨPBX2 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.
Databáze: OpenAIRE
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