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

Barry Hudson, Max H. Stickland, Peter J. Grant, T. Simon Futers

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)2646-2651
Number of pages6
JournalDiabetes
Volume50
Issue number12
StatePublished - Dec 1 2001
Externally publishedYes

Fingerprint

Pseudogenes
Chromosomes, Human, Pair 6
Chromosomes, Human, Pair 3
Nucleic Acid Regulatory Sequences
Sequence Homology
Nucleotides
Genes
Overlapping Genes
Advanced Glycosylation End Product-Specific Receptor
Diabetic Angiopathies
5' Flanking Region
Haploidy
Human Genome
Major Histocompatibility Complex
Chromosomes
DNA

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Internal Medicine

Cite this

@article{23d656db20fc4b49be7e50a927b2ee1f,
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 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.",
author = "Barry Hudson and Stickland, {Max H.} and Grant, {Peter J.} and Futers, {T. Simon}",
year = "2001",
month = "12",
day = "1",
language = "English",
volume = "50",
pages = "2646--2651",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "12",

}

TY - JOUR

T1 - 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

T2 - Implications for polymorphic studies in diabetes

AU - Hudson, Barry

AU - Stickland, Max H.

AU - Grant, Peter J.

AU - Futers, T. Simon

PY - 2001/12/1

Y1 - 2001/12/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0035653506&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035653506&partnerID=8YFLogxK

M3 - Article

C2 - 11723045

AN - SCOPUS:0035653506

VL - 50

SP - 2646

EP - 2651

JO - Diabetes

JF - Diabetes

SN - 0012-1797

IS - 12

ER -