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Spatial gene expression analysis of neuroanatomical differences in mouse models.
Darren J Fernandes1, Jacob Ellegood2, Rand Askalan3
1Mouse Imaging Centre, Hospital for Sick Children, Toronto, ON, Canada; Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
Neuroimage
|September 9, 2017
Summary
Spatial gene expression poorly predicts neuroanatomy changes from single gene mutations. However, analyzing altered neuroanatomy can reveal candidate genes driving these brain differences, particularly in response to environmental enrichment.
Area of Science:
- Neuroscience
- Genetics
- Bioinformatics
Background:
- Magnetic Resonance Imaging (MRI) detects neuroanatomical variations linked to genetic mutations and treatments.
- Identifying causative genes for these neuroanatomical differences is crucial for understanding disease etiology.
- Spatial gene expression data offers a potential avenue for identifying these genes.
Purpose of the Study:
- To evaluate the utility of spatial gene expression data from the Allen Brain Atlas in identifying genes responsible for neuroanatomical differences.
- To explore the relationship between single-gene mutations, spatial gene expression, and resulting neuroanatomical phenotypes in mouse models.
- To investigate candidate gene identification in environmentally induced neuroanatomical changes.
Main Methods:
- Analysis of spatial gene expression patterns in mouse models with single-gene mutations.
- Correlation of altered neuroanatomy with the spatial expression of mutated genes.
- Genome-wide search for genes with preferential spatial expression in neuroanatomically altered regions in response to environmental enrichment.
Main Results:
- Spatial gene expression of mutated genes showed weak association with affected neuroanatomy in many single-gene mutation models.
- Mutated genes exhibited preferential spatial expression in affected neuroanatomy in models with significant differences.
- Environmental enrichment enabled identification of candidate genes related to learning and plasticity through spatial expression analysis in altered brain regions.
Conclusions:
- Spatial gene expression alone is an unreliable predictor of neuroanatomical changes caused by single-gene mutations.
- Neuroanatomical phenotypes can effectively guide the identification of candidate genes underlying these brain alterations.
- This approach holds promise for discovering genes involved in neuroplasticity and learning.

