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Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets

Bergholdt, R; Karlsen, A E; Hagedorn, P. H.; Aalund, M.; Nielsen, J. H.; Kruhoffer, M.; Orntoft, T.; Wang, H.; Wollheim, C. B. and Nerup, Jörn LU , et al. (2007) In Genes and Immunity 8(3). p.232-238
Abstract
We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression... (More)
We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage. (Less)
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publication status
published
subject
keywords
type 1 diabetes, transcriptional profiling, human islets, gene, expression, candidate gene, chromosome 21
in
Genes and Immunity
volume
8
issue
3
pages
232 - 238
publisher
Nature Publishing Group
external identifiers
  • wos:000245970400006
  • scopus:34247574265
ISSN
1476-5470
DOI
10.1038/sj.gene.6364379
language
English
LU publication?
yes
id
6adcf440-48d3-4685-a2b4-9a2a38d39f62 (old id 907987)
date added to LUP
2008-01-09 11:20:32
date last changed
2017-01-01 04:44:02
@article{6adcf440-48d3-4685-a2b4-9a2a38d39f62,
  abstract     = {We recently finemapped a type 1 diabetes (T1D)-linked region on chromosome 21, indicating that one or more T1D-linked genes exist in this region with 33 annotated genes. In the current study, we have taken a novel approach using transcriptional profiling in predicting and prioritizing the most likely candidate genes influencing beta-cell function in this region. Two array-based approaches were used, a rat insulinoma cell line (INS-1 alpha beta) overexpressing pancreatic duodenum homeobox 1 (pdx-1) and treated with interleukin 1 beta (IL-1 beta) as well as human pancreatic islets stimulated with a mixture of cytokines. Several candidate genes with likely functional significance in T1D were identified. Genes showing differential expression in the two approaches were highly similar, supporting the role of these specific gene products in cytokine-induced beta-cell damage. These were genes involved in cytokine signaling, oxidative phosphorylation, defense responses and apoptosis. The analyses, furthermore, revealed several transcription factor binding sites shared by the differentially expressed genes and by genes demonstrating highly similar expression profiles with these genes. Comparable findings in the rat beta-cell line and human islets support the validity of the methods used and support this as a valuable approach for gene mapping and identification of genes with potential functional significance in T1D, within a region of linkage.},
  author       = {Bergholdt, R and Karlsen, A E and Hagedorn, P. H. and Aalund, M. and Nielsen, J. H. and Kruhoffer, M. and Orntoft, T. and Wang, H. and Wollheim, C. B. and Nerup, Jörn and Pociot, F},
  issn         = {1476-5470},
  keyword      = {type 1 diabetes,transcriptional profiling,human islets,gene,expression,candidate gene,chromosome 21},
  language     = {eng},
  number       = {3},
  pages        = {232--238},
  publisher    = {Nature Publishing Group},
  series       = {Genes and Immunity},
  title        = {Transcriptional profiling of type 1 diabetes genes on chromosome 21 in a rat beta-cell line and human pancreatic islets},
  url          = {http://dx.doi.org/10.1038/sj.gene.6364379},
  volume       = {8},
  year         = {2007},
}