Search

Your search keyword '"AFG1L"' showing total 3 results
Start Over Descriptor "AFG1L"
3 results on '"AFG1L"'

1. Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes.

Author

Sahlén, Pelin, Spalinskas, Rapolas, Asad, Samina, Mahapatra, Kunal Das, Höjer, Pontus, Anil, Anandashankar, Eisfeldt, Jesper, Srivastava, Ankit, Nikamo, Pernilla, Mukherjee, Anaya, Kim, Kyu-Han, Bergman, Otto, Ståhle, Mona, Sonkoly, Enikö, Pivarcsi, Andor, Wahlgren, Carl-Fredrik, Nordenskjöld, Magnus, Taylan, Fulya, Bradley, Maria, and Tapia-Páez, Isabel

Abstract

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. 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. 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. 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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

Published
2021
Full Text
View/download PDF

2. Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis– and psoriasis-associated genes

Author

Sahlén, Pelin, Spalinskas, Rapolas, Asad, S., Mahapatra, K. D., Höjer, Pontus, Anil, Anandashankar, Eisfeldt, J., Srivastava, A., Nikamo, P., Mukherjee, A., Kim, K. -H, Bergman, O., Ståhle, M., Sonkoly, E., Pivarcsi, A., Wahlgren, C. -F, Nordenskjöld, M., Taylan, F., Bradley, M., Tapia-Páez, I., Sahlén, Pelin, Spalinskas, Rapolas, Asad, S., Mahapatra, K. D., Höjer, Pontus, Anil, Anandashankar, Eisfeldt, J., Srivastava, A., Nikamo, P., Mukherjee, A., Kim, K. -H, Bergman, O., Ståhle, M., Sonkoly, E., Pivarcsi, A., Wahlgren, C. -F, Nordenskjöld, M., Taylan, F., Bradley, M., and Tapia-Páez, I.

Abstract

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., QC 20210308

Published
2020
Full Text
View/download PDF

3. Chromatin interactions in differentiating keratinocytes reveal novel atopic dermatitis- and psoriasis-associated genes

Author

Pontus Höjer, A. Srivastava, Enikö Sonkoly, Magnus Nordenskjöld, Rapolas Spalinskas, Carl-Fredrik Wahlgren, Kyu-Han Kim, Pelin Sahlén, Anandashankar Anil, Isabel Tapia-Páez, Mona Ståhle, Fulya Taylan, Samina Asad, Jesper Eisfeldt, Maria Bradley, Pernilla Nikamo, Otto Bergman, Kunal Das Mahapatra, Andor Pivarcsi, and Anaya Mukherjee

Subjects
Keratinocytes, Candidate gene, Cell- och molekylärbiologi, Immunology, ADO, Single-nucleotide polymorphism, Genome-wide association study, CLINT1, Computational biology, Biology, Dermatitis, Atopic, Transcriptome, Chromosome conformation capture, Capture Hi-C, 03 medical and health sciences, 0302 clinical medicine, Psoriasis, medicine, Immunology and Allergy, Humans, Genetic Predisposition to Disease, Dermatologi och venereologi, Gene, 030304 developmental biology, Epigenomics, Atopic dermatitis, 0303 health sciences, psoriasis, medicine.disease, Chromatin, Dermatology and Venereal Diseases, LINC00302, AFG1L, RP1-140J1.1, 030217 neurology & neurosurgery, Cell and Molecular Biology
Abstract

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.

Published
2021

Catalog

Books, media, physical & digital resources
See catalog results