Investigating Neuron Degeneration in Huntington's Disease Using RNA-Seq Based Transcriptome Study

Area of Science:

• Neuroscience
• Genetics
• Molecular Biology

Background:

• Huntington's disease (HD) is a progressive neurodegenerative disorder caused by CAG repeat expansion in the huntingtin (HTT) gene.
• Motor dysfunction, including chorea and dystonia, are primary symptoms, originating from the primary motor cortex (BA4).
• Previous research focused on differential gene expression, but the link between variants and gene expression in HD BA4 remains underexplored.

Purpose of the Study:

• To investigate the relationship between genetic variants and differentially expressed genes/transcripts in the primary motor cortex (BA4) of Huntington's disease patients.
• To identify potential regulatory variants affecting gene expression, miRNA targets, and novel genes.
• To understand the functional networks and pathways involved in neurodegeneration in HD.

Main Methods:

• Variant identification and association with gene/transcript quantification.
• Prediction of variant effects on regulatory activities, including miRNA-target interactions.
• Co-expression network and functional interaction network analyses.

Main Results:

• Identified variants associated with differential gene expression in the BA4 region.
• Demonstrated that many variants regulate gene expression and affect miRNA-target interactions.
• Co-expression networks highlighted novel genes, and functional networks emphasized vesicle-mediated transport pathways.

Conclusions:

• Genes expressed in immune cells are proposed as crucial for mitigating neuron death in Huntington's disease.
• This unified approach provides a deeper understanding of the genetic underpinnings of neuron degeneration in HD.
• The findings suggest potential therapeutic targets related to immune response and vesicle transport in HD.