Huntington's Disease

Huntington's disease (HD) is an autosomal dominant genetic disorder caused by expanded CAG repeats in the Huntingtin (HTT) gene. Patients present with progressive neuronal dysfunction, and eventually death. HTT mutations have multiple effects, including loss of anti-apoptotic function as well as altered interactions between HTT and key transcription factors (e.g. SP1 and REST), affecting downstream expression of target genes. For example, HTT sequesters REST in the cytoplasm. Mutant HTT's decreased interaction with REST allows the transcription factor to enter the nucleus and repress BDNF gene expression. BDNF is critical for striatal neuron survival, and its down-regulation leads to neuronal death. Essential processes dysregulated during Huntington’s disease include apoptosis, calcium signaling, and synaptic transmission. Microarray gene expression analyses of human cadavers and mouse HD models have identified many genes that may be involved in HD progression. Some of these genes are also targets for SP1 and/or REST, which may suggest a pathological mechanism of action for this neurodegenerative disease.

QIAGEN provides a broad range of assay technologies for Huntington’s disease research that enables analysis of gene expression and regulation, epigenetic modification, genotyping, and signal transduction pathway activation. Solutions optimized for Huntington’s disease studies include PCR array, miRNA, siRNA, mutation analysis, pathway reporter, chromatin IP, DNA methylation, and protein expression products.