DNA methylation study of Huntington’s disease and motor progression in patients and in animal models

Although Huntington’s disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, an...

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Bibliographic Details
Published in:Nature communications 2020-09, Vol.11 (1), p.4529-4529, Article 4529
Main Authors: Lu, Ake T., Narayan, Pritika, Grant, Matthew J., Langfelder, Peter, Wang, Nan, Kwak, Seung, Wilkinson, Hilary, Chen, Richard Z., Chen, Jian, Simon Bawden, C., Rudiger, Skye R., Ciosi, Marc, Chatzi, Afroditi, Maxwell, Alastair, Hore, Timothy A., Aaronson, Jeff, Rosinski, Jim, Preiss, Alicia, Vogt, Thomas F., Coppola, Giovanni, Monckton, Darren, Snell, Russell G., William Yang, X., Horvath, Steve
Format: Article
Language:English
Subjects:
42
45
631/208/176/1988
631/208/177
631/337/176
631/378/1689/1558
692/699/375/1558
Adolescent
Adult
Aged
Aged, 80 and over
Animal models
Animals
Animals, Genetically Modified
Behavior, Animal
CpG islands
CpG Islands - genetics
Cross-Sectional Studies
Deoxyribonucleic acid
Disease Models, Animal
Disease Progression
DNA
DNA Methylation
Epigenesis, Genetic
Epigenetics
Female
Follow-Up Studies
Gene Knock-In Techniques
Genetic disorders
Genetic Loci
Genome-Wide Association Study
Global Burden of Disease
Humanities and Social Sciences
Humans
Huntingtin
Huntingtin Protein - genetics
Huntington Disease - blood
Huntington Disease - diagnosis
Huntington Disease - epidemiology
Huntington Disease - genetics
Huntington's disease
Huntingtons disease
Longitudinal Studies
Male
Mice
Middle Aged
multidisciplinary
Mutation
Prospective Studies
Recombinant Proteins - genetics
Registries - statistics & numerical data
Science
Science (multidisciplinary)
Severity of Illness Index
Sheep
Species
Young Adult
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Summary:Although Huntington’s disease (HD) is a well studied Mendelian genetic disorder, less is known about its associated epigenetic changes. Here, we characterize DNA methylation levels in six different tissues from 3 species: a mouse huntingtin (Htt) gene knock-in model, a transgenic HTT sheep model, and humans. Our epigenome-wide association study (EWAS) of human blood reveals that HD mutation status is significantly ( p  
ISSN:2041-1723
2041-1723
DOI:10.1038/s41467-020-18255-5