Discrepancies in gene expression pattern data: Sample preparation
|
| Sample User Question
|  |
| Recent literature has suggested that
mutant huntingtin (HD) proteins seen in the neurodegenerative Huntington
Disease may act by disrupting transcription initiation complexes.
This disruptive effect is at the level of general transcription factor
interactions associated with the TATA site found in nearly all eukaryotic
genes. This might suggest that the specificity seen in neurodegeneration
associated with Huntington Disease reflect the tissue specific expression
pattern of the huntingtin gene. If this were true, we might expect
that huntingtin would only be expressed in neural tissues. Using the
various expression resources we have explored in this module, test this hypothesis. |
| Step By Step Guide |
|
- Do a search for huningtin (HD) expression in the Human Protein Atlas, UniGene, and the Sage Anatomical Viewer
- Each if these indicates that huntingin is expressed in a variety of tissues other than neural or brain.
- In particular, in the SAGE data from the Anatomic Viewer, there appears o be a discrepancy--when one views the whole body data, only normal brain shows a signal, but when both body and cellular data are examined together huntingtin is clearly expressed in normal pancreas...
- An examination of the list of cells used to aquire the SAGE data indicates that culured Beta Cells from the pancreas are express HD, and when inclused are responsible for the signal seen.
- Similarly, both UniGene Profiler and the Human Protein Atlas show that there is expression of both HD RNA and protein in a variety of non-neural tissues. The Protein Atlas further confirms the SAGE result by showing that in pancras the HD protein product is found in the islets.
- Thus, simple expression pattern of HD alone is not adiquae to explain HD's association with neural degenrative diseases.
- However, in the case of the expression seen in the islets in pancras, it is interesting to note that it is well known that individuals suffereing from Huntington Disease also have 7 times the occurance of Type I Diabetes seen in the non-diseased popuation and this is due to degradation of Beta Cells in the pancreas. This suggests possibly a common mechanism for cell degeneration and a possble role for transcription disruption in this tissue as well
Again, we see such issues as tissue origin, definition, handling and biological context as critical in interpreting expression data...
|
|
