Transcriptomics

Dataset Information

6

Transcription profiling by array of human BMPR2 mutation carriers with and without evidence of pulmonary arterial hypertension


ABSTRACT: Background: While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH), only 20% of mutation carriers develop clinical disease. This finding suggests that modifier genes contribute to FPAH clinical expression. Since modifiers are likely to be common alleles, this problem is not tractable by traditional genetic approaches. Further, examination of gene expression is complicated by confounding effects attributable to drugs and the disease process itself. Methods: To resolve these problems, B-cells were isolated, EBV-immortalized, and cultured from familial PAH patients with BMPR2 mutations, mutation positive but disease-free family members, and family members without mutation. This allows examination of differences in gene expression without drug or disease-related effects. These differences were assayed by Affymetrix array, with follow-up by quantitative RT-PCR and additional statistical analyses. Results: By gene array, we found consistent alterations in multiple pathways with known relationship to PAH, including actin organization, immune function, calcium balance, growth, and apoptosis. Selected genes were verified by quantitative RT-PCR using a larger sample set. Analysis of overrepresented gene ontology groups suggests that it is pathway-specific, not gene-specific changes that carry increased risk of disease. Conclusions: B-cell lines are a valuable and accessible tool for assaying alterations in gene expression free from drug and disease effects. Predisposition to disease within BMPR2 mutation carriers was linked to several pathways, including proliferation, GTP signaling, and stress response. Experiment Overall Design: Immortalized B-cells from BMPR2 mutation carriers with and without disease are compared to search for modifier genes

REANALYSED by: E-GEOD-10767

INSTRUMENT(S): 418 [Affymetrix]

ORGANISM(S): Homo sapiens  

SUBMITTER: James West  

PROVIDER: E-GEOD-10767 | ArrayExpress | 2008-10-25

SECONDARY ACCESSION(S): GSE10767PRJNA107557

REPOSITORIES: GEO, ArrayExpress

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Publications

Gene expression in BMPR2 mutation carriers with and without evidence of pulmonary arterial hypertension suggests pathways relevant to disease penetrance.

West James J   Cogan Joy J   Geraci Mark M   Robinson Linda L   Newman John J   Phillips John A JA   Lane Kirk K   Meyrick Barbara B   Loyd Jim J  

BMC medical genomics 20080929


BACKGROUND:While BMPR2 mutation strongly predisposes to pulmonary arterial hypertension (PAH), only 20% of mutation carriers develop clinical disease. This finding suggests that modifier genes contribute to FPAH clinical expression. Since modifiers are likely to be common alleles, this problem is not tractable by traditional genetic approaches. Furthermore, examination of gene expression is complicated by confounding effects attributable to drugs and the disease process itself. METHODS:To resolv  ...[more]

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