Genetic architecture of early pre-inflammatory stage transcription signatures of autoimmune diabetes in the pancreatic lymph nodes of the NOD mouse reveals significant gene enrichment on chromosomes 6 and 7.Report as inadecuate




Genetic architecture of early pre-inflammatory stage transcription signatures of autoimmune diabetes in the pancreatic lymph nodes of the NOD mouse reveals significant gene enrichment on chromosomes 6 and 7. - Download this document for free, or read online. Document in PDF available to download.

* Corresponding author 1 Génotypage des Eucaryotes Plate-Forme 2 Département Parasites et Insectes vecteurs

Abstract : Autoimmune diseases are characterized by the stimulation of an excessive immune response to self-tissues by inner and-or outer organism factors. Common characteristics in their etiology include a complex genetic predisposition and environmental triggers as well as the implication of the major histocompatibility MHC locus on human chromosome 6p21. A restraint number of non-MHC susceptibility genes, part of the genetic component of type 1 diabetes have been identified in human and in animal models, while the complete spectrum of genes involved remains unknown. We elaborate herein patterns of chromosomal organization of 162 genes differentially expressed in the pancreatic lymph nodes of Non-Obese Diabetic mice, carefully selected by early sub-phenotypic evaluation presence or absence of insulin autoantibodies. Chromosomal assignment of these genes revealed a non-random distribution on five chromosomes 47%. Significant gene enrichment was observed in particular for two chromosomes, 6 and 7. While a subset of these genes coding for secreted proteins showed significant enrichment on both chromosomes, the overall pool of genes was significantly enriched on chromosome 7. The significance of this unexpected gene distribution on the mouse genome is discussed in the light of novel findings indicating that genes affecting common diseases map to recombination -hotspot- regions of mammalian genomes. The genetic architecture of transcripts differentially expressed in specific stages of autoimmune diabetes offers novel venues towards our understanding of patterns of inheritance potentially affecting the pathological disease mechanisms.

Keywords : Type 1 diabetes Transcriptome Genomics Pancreatic lymph nodes Polymorphisms





Author: Beatrice Regnault - Evie Melanitou -

Source: https://hal.archives-ouvertes.fr/



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