Unknown,Transcriptomics,Genomics,Proteomics

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Gene Array Analyzer (GAA): Alternative usage of gene arrays to study alternative splicing events (MoGene array)

ABSTRACT: The latest version of microarrays released by Affymetrix, the GeneChip Gene 1.0 ST Arrays (gene arrays), are designed in a similar fashion as exon arrays, which enables to identify differentially expressed exons, rather than only the expression level of whole transcripts. Here, we propose an extension, Gene Array Analyzer (GAA), to our previously published Exon Array Analyzer (EAA). GAA enables to analyse gene arrays on exon level and therefore supports to identify alternative splicing with gene arrays. To show the applicability of GAA, we used gene arrays to profile alternative splice events during the development of the heart. Further re-analysis of published gene arrays could show, that some of these splice events reoccur under pathological conditions. The web interface of GAA is user friendly, functional without set up and freely available at http://GAA.mpi-bn.mpg.de. Alternative splicing and gene expression analysis during development of the heart and cardiomyoyte differentiation.

ORGANISM(S): Mus musculus

SUBMITTER: Pascal Gellert

PROVIDER: E-GEOD-30429 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Gene Array Analyzer: alternative usage of gene arrays to study alternative splicing events.

Gellert Pascal P Teranishi Mizue M Jenniches Katharina K De Gaspari Piera P John David D Kreymborg Karsten grosse Kg Braun Thomas T Uchida Shizuka S

Nucleic acids research 20111128 6

Exon arrays are regularly used to analyze differential splicing events. GeneChip Gene 1.0 ST Arrays (gene arrays) manufactured by Affymetrix, Inc. are primarily used to determine expression levels of transcripts, although their basic design is rather similar to GeneChip Exon 1.0 ST Arrays (exon arrays). Here, we show that the newly developed Gene Array Analyzer (GAA), which evolved from our previously published Exon Array Analyzer (EAA), enables economic and user-friendly analysis of alternative ...[more]

PMID: 22123740

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Project description:In non-neuronopathic type 1 Gaucher disease (GD1) mutations in GBA1 gene results in deficiency of glucocerebrosidase and the accumulation of glucocerebroside in lysosomes of mononuclear phagocytes. The metabolic defect leads to a complex phenotype involving the viscera, the bone marrow and the skeleton. However the prevailing macrophage-centric view of the disease does not explain emerging aspects of the disease such as hematological malignancies, autoimmune diathesis, ParkinsonM-bM-^@M-^Ys disease and osteoporosis poorly responsive to macrophage targeted enzyme therapy or anti-resorptive therapies. We developed a conditional KO mouse model of GD1 to delineate cells and pathways in GD1. By targeting the cells of the hematopoetic and mesenchymal cell lineages through an Mx1 promoter, we recapitulated human GD1. We show that, in addition to significant visceral and hematologic disease, GD1 mice show profound osteopenia due to a bone formation defect. Cytokine measurements, microarray analysis and cellular immunophenotyping together point to widespread dysfunction of macrophages and other immune cells together with a striking abnormality in thymic T-cell development. Our study provides the first direct evidence for the involvement of cell lineages other than mononuclear phagocytes, most notably osteoblasts and T cells, in the pathophysiology of the clinical spectrum of type 1 GD. These findings have important implications for treatment of GD1. We hypothesize that regulation of gene expression is different in Gaucher disease compared with the normal controls. This difference may even be evident in the different stages of this disease. In order to gain insight to the genes that are potentially involved in the development of Gaucher disease in its different clinical stages, exon-array is chosen for this genome-wide association studies. Mouse liver and spleen samples from normal control, GD with moderate to severe splenomegaly/hepatomegaly, together nine samples were chosen. The goal is to find out genes of which the expression may relate to the GD or the severity of GD and thus help identify genetic modifier genes that may contribute to the onset and development of Gaucher disease.

Dataset Information

Gene Array Analyzer (GAA): Alternative usage of gene arrays to study alternative splicing events (MoGene array)

Publications

Gene Array Analyzer: alternative usage of gene arrays to study alternative splicing events.

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