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A genetic-epigeneti...
A genetic-epigenetic interplay at 1q21.1 locus underlies CHD1L-mediated vulnerability to primary progressive multiple sclerosis
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- Kakhki, Majid Pahlevan (author)
- Karolinska Inst, Sweden
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- Giordano, Antonino (author)
- Karolinska Inst, Sweden; IRCCS San Raffaele Hosp, Italy; IRCCS San Raffaele Hosp, Italy; IRCCS San Raffaele Sci Inst, Italy; Univ Vita Salute San Raffaele, Italy
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- Cucuzza, Chiara Starvaggi (author)
- Karolinska Inst, Sweden; Acad Specialist Ctr, Sweden
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- Badam, Tejaswi (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten,Karolinska Inst, Sweden
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- Samudyata, Samudyata (author)
- Karolinska Inst, Sweden
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- Lemee, Marianne Victoria (author)
- Inst Genet & Biol Mol & Cellulaire, France; Ctr Natl Rech Sci, France; Inst Natl Sante & Rech Med, France; Univ Strasbourg, France
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- Stridh, Pernilla (author)
- Karolinska Inst, Sweden
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- Gkogka, Asimenia (author)
- Karolinska Inst, Sweden
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- Shchetynsky, Klementy (author)
- Karolinska Inst, Sweden
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- Harroud, Adil (author)
- Neuro Montreal Neurol Inst Hosp, Canada; McGill Univ, Canada; McGill Univ, Canada
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- Gyllenberg, Alexandra (author)
- Karolinska Inst, Sweden
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- Liu, Yun (author)
- Fudan Univ, Peoples R China
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- Boddul, Sanjaykumar (author)
- Karolinska Inst, Sweden
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- James, Tojo (author)
- Karolinska Inst, Sweden
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- Sorosina, Melissa (author)
- IRCCS San Raffaele Sci Inst, Italy
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- Filippi, Massimo (author)
- IRCCS San Raffaele Hosp, Italy; IRCCS San Raffaele Hosp, Italy; Univ Vita Salute San Raffaele, Italy; IRCCS San Raffaele Hosp, Italy; IRCSS San Raffaele Sci Inst, Italy
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- Esposito, Federica (author)
- IRCCS San Raffaele Hosp, Italy; IRCCS San Raffaele Hosp, Italy; IRCCS San Raffaele Sci Inst, Italy
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- Wermeling, Fredrik (author)
- Karolinska Inst, Sweden
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- Gustafsson, Mika (author)
- Linköpings universitet,Bioinformatik,Tekniska fakulteten
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- Casaccia, Patrizia (author)
- Icahn Sch Med Mt Sinai, NY USA
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- Hillert, Jan (author)
- Karolinska Inst, Sweden
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- Olsson, Tomas (author)
- Karolinska Inst, Sweden
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- Kockum, Ingrid (author)
- Karolinska Institutet
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- Sellgren, Carl M. (author)
- Karolinska Inst, Sweden; Karolinska Inst, Sweden; Stockholm Cty Council, Sweden
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- Golzio, Christelle (author)
- Inst Genet & Biol Mol & Cellulaire, France; Ctr Natl Rech Sci, France; Inst Natl Sante & Rech Med, France; Univ Strasbourg, France
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- Kular, Lara (author)
- Karolinska Inst, Sweden
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- Jagodic, Maja (author)
- Karolinska Inst, Sweden
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(creator_code:org_t)
- NATURE PORTFOLIO, 2024
- 2024
- English.
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In: Nature Communications. - : NATURE PORTFOLIO. - 2041-1723. ; 15:1
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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http://kipublication...
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http://kipublication...
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Abstract
Subject headings
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- Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts. In PPMS, we found hypermethylation of the 1q21.1 locus, controlled by PPMS-specific genetic variations and influencing the expression of proximal genes (CHD1L, PRKAB2) in the brain. Evidence from reporter assay and CRISPR/dCas9 experiments supports a causal link between methylation and expression and correlation network analysis further implicates these genes in PPMS brain processes. Knock-down of CHD1L in human iPSC-derived neurons and knock-out of chd1l in zebrafish led to developmental and functional deficits of neurons. Thus, several lines of evidence suggest a distinct genetic-epigenetic-transcriptional interplay in the 1q21.1 locus potentially contributing to PPMS pathogenesis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kakhki, Majid Pa ...
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Giordano, Antoni ...
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Cucuzza, Chiara ...
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Badam, Tejaswi
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Samudyata, Samud ...
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Lemee, Marianne ...
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show more...
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Stridh, Pernilla
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Gkogka, Asimenia
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Shchetynsky, Kle ...
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Harroud, Adil
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Gyllenberg, Alex ...
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Liu, Yun
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Boddul, Sanjayku ...
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James, Tojo
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Sorosina, Meliss ...
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Filippi, Massimo
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Esposito, Federi ...
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Wermeling, Fredr ...
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Gustafsson, Mika
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Casaccia, Patriz ...
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Hillert, Jan
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Olsson, Tomas
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Kockum, Ingrid
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Sellgren, Carl M ...
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Golzio, Christel ...
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Kular, Lara
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Jagodic, Maja
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Nature Communica ...
- By the university
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Linköping University
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Karolinska Institutet