Biomaterial Database

DNA methylation in Huntington's disease: Implications for transgenerational effects. 2016

Elizabeth A Thomas

Department of Molecular and Cellular Neuroscience, The Scripps Research Institute, La Jolla, CA, United States. Electronic address: bthomas@scripps.edu.

Huntington's disease (HD) is a devastating, neurodegenerative disorder caused by a CAG repeat mutation in the HTT gene. A growing body of evidence suggests that epigenetic modifications play a key role in HD pathogenesis. Expression of the disease protein, huntingtin, leads to extensive transcriptional dysregulation due to disruption of histone-modifying complexes and altered interactions with chromatin-related factors. Such epigenetic mechanisms also readily respond to environmental factors, which are now thought to influence the risk, onset and progression of neurodegenerative disorders, including HD. DNA methylation is an epigenetic modification that has been studied intensively, however, its role in HD is just emerging. In this review, DNA methylation differences associated with HD will be summarized, as well as the role of environmental factors to alter DNA methylation in a manner that could alter disease phenotypes. Further, transgenerational epigenetic inheritance will be discussed in the context of relevant environmental factors and their potential links to HD. The study of epigenetic states in HD presents an opportunity to gain new insights into risk factors and pathogenic mechanisms associated with HD, as well as to inform about treatment options.

UI	MeSH Term	Description	Entries
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D006816	Huntington Disease	A familial disorder inherited as an autosomal dominant trait and characterized by the onset of progressive CHOREA and DEMENTIA in the fourth or fifth decade of life. Common initial manifestations include paranoia; poor impulse control; DEPRESSION; HALLUCINATIONS; and DELUSIONS. Eventually intellectual impairment; loss of fine motor control; ATHETOSIS; and diffuse chorea involving axial and limb musculature develops, leading to a vegetative state within 10-15 years of disease onset. The juvenile variant has a more fulminant course including SEIZURES; ATAXIA; dementia; and chorea. (From Adams et al., Principles of Neurology, 6th ed, pp1060-4)	Huntington Chorea,Juvenile Huntington Disease,Akinetic-Rigid Variant of Huntington Disease,Chorea, Chronic Progressive Hereditary (Huntington),Chronic Progressive Hereditary Chorea (Huntington),Huntington Chronic Progressive Hereditary Chorea,Huntington Disease, Akinetic-Rigid Variant,Huntington Disease, Juvenile,Huntington Disease, Juvenile-Onset,Huntington Disease, Late Onset,Huntington's Chorea,Huntington's Disease,Juvenile-Onset Huntington Disease,Late-Onset Huntington Disease,Progressive Chorea, Chronic Hereditary (Huntington),Progressive Chorea, Hereditary, Chronic (Huntington),Akinetic Rigid Variant of Huntington Disease,Chorea, Huntington,Chorea, Huntington's,Huntington Disease, Akinetic Rigid Variant,Huntington Disease, Juvenile Onset,Huntington Disease, Late-Onset,Juvenile Onset Huntington Disease,Late Onset Huntington Disease
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013315	Stress, Psychological	Stress wherein emotional factors predominate.	Cumulative Stress, Psychological,Emotional Stress,Individual Stressors,Life Stress,Psychological Cumulative Stress,Psychological Stress Experience,Psychological Stress Overload,Psychologically Stressful Conditions,Stress Experience, Psychological,Stress Measurement, Psychological,Stress Overload, Psychological,Stress Processes, Psychological,Stress, Emotional,Stressful Conditions, Psychological,Psychological Stress,Stress, Psychologic,Stressor, Psychological,Condition, Psychological Stressful,Condition, Psychologically Stressful,Conditions, Psychologically Stressful,Cumulative Stresses, Psychological,Experience, Psychological Stress,Individual Stressor,Life Stresses,Measurement, Psychological Stress,Overload, Psychological Stress,Psychologic Stress,Psychological Cumulative Stresses,Psychological Stress Experiences,Psychological Stress Measurement,Psychological Stress Measurements,Psychological Stress Overloads,Psychological Stress Processe,Psychological Stress Processes,Psychological Stresses,Psychological Stressful Condition,Psychological Stressful Conditions,Psychological Stressor,Psychological Stressors,Psychologically Stressful Condition,Stress Experiences, Psychological,Stress Processe, Psychological,Stress, Life,Stress, Psychological Cumulative,Stressful Condition, Psychological,Stressful Condition, Psychologically,Stressor, Individual
D015870	Gene Expression	The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.	Expression, Gene,Expressions, Gene,Gene Expressions
D044127	Epigenesis, Genetic	A genetic process by which the adult organism is realized via mechanisms that lead to the restriction in the possible fates of cells, eventually leading to their differentiated state. Mechanisms involved cause heritable changes to cells without changes to DNA sequence such as DNA METHYLATION; HISTONE modification; DNA REPLICATION TIMING; NUCLEOSOME positioning; and heterochromatization which result in selective gene expression or repression.	Epigenetic Processes,Epigenetic Process,Epigenetics Processes,Genetic Epigenesis,Process, Epigenetic,Processes, Epigenetic,Processes, Epigenetics
D059647	Gene-Environment Interaction	The combined effects of genotypes and environmental factors together on phenotypic characteristics.	Environment-Gene Interaction,Environment Gene Interaction,Environment-Gene Interactions,Gene Environment Interaction,Gene-Environment Interactions,Interaction, Environment-Gene,Interaction, Gene-Environment,Interactions, Environment-Gene,Interactions, Gene-Environment
D019175	DNA Methylation	Addition of methyl groups to DNA. DNA methyltransferases (DNA methylases) perform this reaction using S-ADENOSYLMETHIONINE as the methyl group donor.	DNA Methylations,Methylation, DNA,Methylations, DNA