Cell-type-specific neuroanatomy of cliques of autism-related genes in the mouse brain

Frontiers in Computational Neuroscience

Mike eHawrylycz¹  Idan eMenashe²  Pascal eGrange³ 

[1] Allen Institute for Brain Science;Ben-Gurion University of the Negev;Xi'An Jiaotong-Liverpool University;

关键词: Cerebellum;    Gene Expression;    Autism Spectrum Disorder;    Computational Neuroanatomy;    cell types;   

DOI  :  10.3389/fncom.2015.00055

来源: DOAJ

【 摘 要 】

Two cliquesof genes identified computationally for their high co-expression in themouse brain accordingto the Allen Brain Atlas, and for their enrichment in genes related to autism spectrum disorder, have recentlybeen shown to be highly co-expressed in the cerebellar cortex, compared to what could be expectedby chance. Moreover, the expression of these cliques of genes is not homogeneous across the cerebellar cortex, and it has been noted that their expression pattern seems to highlight the granular layer. However, this observation was only made by eye, and recent advances in computational neuroanatomy allow to rank cell types in the mouse brain (characterized by their transcriptome profiles) according to the similarity between their spatial density profiles and the expression profiles of the cliques. We establish by Monte Carlo simulation that with probability at least 99%, the expression profiles of the two cliques are more similar to the density profile of granule cells than 99% of the expression of cliques containing the same number of genes (Purkinje cells also score above 99% in one of the cliques).Thresholding the expression profiles shows that the signal is more intense in the granular layer. Finally, we work out pairs of cell types whose combined expression profiles are more similar to the expression profiles of the cliquesthan any single cell type. These pairs predominantly consist of one cortical pyramidal cell and one cerebellar cell (whichcan be either a granule cell or a Purkinje cell).

【 授权许可】

Unknown