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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Veröffentlicht in:	Nature communications 2020-09, Vol.11 (1), p.4529-4529, Article 4529
Hauptverfasser:	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:	Artikel
Sprache:	eng
Schlagworte:	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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Zusammenfassung:	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