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Chromatin interacti...
Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes
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- Sahlén, Pelin (author)
- KTH,Science for Life Laboratory, SciLifeLab,Genteknologi
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- Spalinskas, Rapolas, Dr. 1983- (author)
- KTH,Science for Life Laboratory, SciLifeLab,Skolan för kemi, bioteknologi och hälsa (CBH)
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- Asad, S. (author)
- Karolinska Institutet
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- Mahapatra, K. D. (author)
- Karolinska Institutet
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- Höjer, Pontus (author)
- KTH,Genteknologi
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- Anil, Anandashankar (author)
- KTH,Science for Life Laboratory, SciLifeLab
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- Eisfeldt, J. (author)
- Karolinska Institutet
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Srivastava, A. (author)
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- Nikamo, P. (author)
- Karolinska Institutet
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Mukherjee, A. (author)
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Kim, K. -H (author)
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- Bergman, O. (author)
- Karolinska Institutet
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- Ståhle, M. (author)
- Karolinska Institutet
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- Sonkoly, Enikö (author)
- Karolinska Institutet
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- Pivarcsi, Andor (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Dermatology and Venereology Division, Department of Medicine Solna, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
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- Wahlgren, C. -F (author)
- Karolinska Institutet
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- Nordenskjöld, M. (author)
- Karolinska Institutet
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- Taylan, F. (author)
- Karolinska Institutet
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- Bradley, M. (author)
- Karolinska Institutet
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- Tapia-Páez, I. (author)
- Karolinska Institutet
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(creator_code:org_t)
- Mosby Inc. 2020
- 2020
- English.
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In: Journal of Allergy and Clinical Immunology. - : Mosby Inc.. - 0091-6749 .- 1097-6825.
- Related links:
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https://doi.org/10.1...
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http://www.jacionlin...
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https://uu.diva-port... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://urn.kb.se/re...
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http://kipublication...
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http://kipublication...
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Abstract
Subject headings
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- Background: Hundreds of variants associated with atopic dermatitis (AD) and psoriasis, 2 common inflammatory skin disorders, have previously been discovered through genome-wide association studies (GWASs). The majority of these variants are in noncoding regions, and their target genes remain largely unclear. Objective: We sought to understand the effects of these noncoding variants on the development of AD and psoriasis by linking them to the genes that they regulate. Methods: We constructed genomic 3-dimensional maps of human keratinocytes during differentiation by using targeted chromosome conformation capture (Capture Hi-C) targeting more than 20,000 promoters and 214 GWAS variants and combined these data with transcriptome and epigenomic data sets. We validated our results with reporter assays, clustered regularly interspaced short palindromic repeats activation, and examination of patient gene expression from previous studies. Results: We identified 118 target genes of 82 AD and psoriasis GWAS variants. Differential expression of 58 of the 118 target genes (49%) occurred in either AD or psoriatic lesions, many of which were not previously linked to any skin disease. We highlighted the genes AFG1L, CLINT1, ADO, LINC00302, and RP1-140J1.1 and provided further evidence for their potential roles in AD and psoriasis. Conclusions: Our work focused on skin barrier pathology through investigation of the interaction profile of GWAS variants during keratinocyte differentiation. We have provided a catalogue of candidate genes that could modulate the risk of AD and psoriasis. Given that only 35% of the target genes are the gene nearest to the known GWAS variants, we expect that our work will contribute to the discovery of novel pathways involved in AD and psoriasis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Dermatologi och venereologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Dermatology and Venereal Diseases (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- ADO
- AFG1L
- Atopic dermatitis
- Capture Hi-C
- CLINT1
- LINC00302
- psoriasis
- RP1-140J1.1
Publication and Content Type
- ref (subject category)
- art (subject category)
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To the university's database
- By the author/editor
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Sahlén, Pelin
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Spalinskas, Rapo ...
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Asad, S.
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Mahapatra, K. D.
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Höjer, Pontus
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Anil, Anandashan ...
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show more...
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Eisfeldt, J.
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Srivastava, A.
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Nikamo, P.
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Mukherjee, A.
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Kim, K. -H
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Bergman, O.
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Ståhle, M.
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Sonkoly, Enikö
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Pivarcsi, Andor
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Wahlgren, C. -F
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Nordenskjöld, M.
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Taylan, F.
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Bradley, M.
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Tapia-Páez, I.
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Dermatology and ...
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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 Cell and Molecul ...
- Articles in the publication
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Journal of Aller ...
- By the university
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Royal Institute of Technology
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Uppsala University
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Karolinska Institutet