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

Författare

  • R Bergholdt
  • A E Karlsen
  • P. H. Hagedorn
  • M. Aalund
  • J. H. Nielsen
  • M. Kruhoffer
  • T. Orntoft
  • H. Wang
  • C. B. Wollheim
  • Jörn Nerup
  • F Pociot

Summary, in English

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.

Publiceringsår

2007

Språk

Engelska

Sidor

232-238

Publikation/Tidskrift/Serie

Genes and Immunity

Volym

8

Issue

3

Dokumenttyp

Artikel i tidskrift

Förlag

Nature Publishing Group

Ämne

  • Other Clinical Medicine

Nyckelord

  • type 1 diabetes
  • transcriptional profiling
  • human islets
  • gene
  • expression
  • candidate gene
  • chromosome 21

Status

Published

ISBN/ISSN/Övrigt

  • ISSN: 1476-5470