Computational Analysis of Transcriptional Regulation Sites at the HTT Gene Locus.

Background: Huntington's disease is a late onset neurological disorder caused by a trinucleotide CAG repeat expansion mutation in the HTT gene encoding for the protein huntingtin. Despite considerable ongoing research, the wild-type function of huntingtin is not yet fully understood.

Objective: To improve knowledge of HTT gene regulation at the transcriptional level and inform future studies aimed at uncovering the HTT gene's normal function.

Microfluidic Production and Application of Lipid Nanoparticles for Nucleic Acid Transfection.

Lipid nanoparticles (LNPs) are established in the biopharmaceutical industry for efficient encapsulation and cytosolic delivery of nucleic acids for potential therapeutics, with several formulations in clinical trials. The advantages of LNPs can also be applied in basic research and discovery with a microfluidic method of preparation now commercially available that allows preparations to be scaled down to quantities appropriate for cell culture. These preparations conserve expensive nucleic acids while maintaining the particle characteristics that have made LNPs successful in later stages of genetic medicine development.

DNA methylation profiling in human Huntington's disease brain.

Despite extensive progress in Huntington's disease (HD) research, very little is known about the association of epigenetic variation and HD pathogenesis in human brain tissues. Moreover, its contribution to the tissue-specific transcriptional regulation of the huntingtin gene (HTT), in which HTT expression levels are highest in brain and testes, is currently unknown. To investigate the role of DNA methylation in HD pathogenesis and tissue-specific expression of HTT, we utilized the Illumina HumanMethylation450K BeadChip array to measure DNA methylation in a cohort of age-matched HD and control human cortex and liver tissues.

A SNP in the HTT promoter alters NF-κB binding and is a bidirectional genetic modifier of Huntington disease.

Cis-regulatory variants that alter gene expression can modify disease expressivity, but none have previously been identified in Huntington disease (HD). Here we provide in vivo evidence in HD patients that cis-regulatory variants in the HTT promoter are bidirectional modifiers of HD age of onset. HTT promoter analysis identified a NF-κB binding site that regulates HTT promoter transcriptional activity.

Neurobiology of Huntington's Disease.

Of the neurodegenerative diseases presented in this book, Huntington's disease (HD) stands as the archetypal autosomal dominantly inherited neurodegenerative disorder. Its occurrence through generations of affected families was noted long before the basic genetic underpinnings of hereditary diseases was understood. The early classification of HD as a distinct hereditary neurodegenerative disorder allowed the study of this disease to lead the way in the development of our understanding of the mechanisms of human genetic disorders.