Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 145, Issue 6, Pages 806-815Publisher
WILEY-BLACKWELL
DOI: 10.1111/j.1365-2141.2009.07692.x
Keywords
Shwachman-Diamond syndrome; ribosomal proteins; gene expression; microarray; bone marrow failure
Categories
Funding
- Canadian Institute of Health [MOP57720]
- Shwachman-Diamond Syndrome International
- Anemia Institute for Research and Education
- Royal Thai Army
Ask authors/readers for more resources
Shwachman-Diamond Syndrome (SDS) is a multi-system genetic disorder with bone marrow failure. SBDS, the gene associated with SDS, has been postulated to play a role in ribosome biogenesis and RNA processing, but its functions are still unknown. To study whether these pathways are interrupted when Sbds protein is lost, we studied the expression of related genes in patient SBDS-/- cells by an oligonucleotide microarray. We first analysed ribosomal protein (RP) genes, which are normally co-regulated. In SDS, 27 of the 85 RP genes were downregulated. Among the downregulated RP genes, seven are known to be associated with the inhibition of apoptosis. RPS27L, which mediates p53-dependent induction of apoptosis, was the only upregulated RP gene. Interestingly, several genes involved in RP mRNA transcription were downregulated without affecting the expression of genes involved in mRNA degradation, suggesting that the downregulation of the RP gene expression might be at the transcriptional level. Importantly we also found dysregulation of multiple genes involved in rRNA transcription and pre-rRNA processing. We conclude that SDS marrow cells exhibit major dysregulation of RP, RNA processing and RNA transcription genes.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available