Long-read sequencing of
10 affiliations
- 1Laboratory of Human Genetics, GIGA Research Institute, Liège, Belgium;; Center of Genetics, University Hospital, Liège, Belgium
- 2Center of Genetics, University Hospital, Liège, Belgium
- 3Department of Pediatric Dermatology, Clinique CHC MontLegia, Liège, Belgium
- 4Center for Medical Genetics, Institut de Pathologie et de Génétique Gosselies, Charleroi, Belgium
- 5Dermatology and Genetic Medicine, Division of Biological Chemistry and Drug Discovery, School of Life Sciences, University of Dundee, Dundee, United Kingdom
- 6Clinical Medicine, Trinity College Dublin, Dublin, Ireland
- 7Department of Biochemistry, Molecular Biology and Genetics, University of Rwanda, Kigali, Rwanda
- 8Department of Dermatology, Centre Hospitalier University of Kigali (CHUK), Kigali, Rwanda
- 9Theratopix Pharma S.A., Liège, Belgium
- 10Laboratory of Human Genetics, GIGA Research Institute, Liège, Belgium;; Center of Genetics, University Hospital, Liège, Belgium; Correspondence: Keith Durkin, Human Genetics, University of Liège, CHU - B34, Quartier Hôpital, Avenue de l'Hôpital, 1, Liège 4000, Belgium.
Abstract
Loss-of-function (LOF) variants of the FLG gene are risk factors for atopic dermatitis. However, owing to the repetitive nature of exon 3, these variants are difficult to characterize. We sought to determine whether the use of long-read technologies would enable better characterization of the FLG gene and improve the detection of LOF variants. We sequenced a diverse clinical cohort of 192 samples collected in Belgium, Ireland, and Rwanda using long-read sequencing as well as publicly available data. We identified both common and rare LOF variants linked to atopic dermatitis in our clinical cohort, a number of compound heterozygotes, as well as 1 previously undescribed LOF variant. We also observed 20 previously undescribed FLG alleles, which varied in length by up to 13 kb. These were mostly found in samples of sub-Saharan origin and appear to be products of nonallelic homologous recombination. Despite the use of a long-read–based approach, we did not detect any FLG LOF variants in our African cohort, highlighting differences in FLG LOF burden and atopic dermatitis genetic risk between populations. Our approach has the potential to be a useful tool to identify FLG variants contributing to atopic dermatitis in various human populations.
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BibTeX
@article{grentzinger2026longread,
title = {{Long-read sequencing of}},
author = {Victor Grentzinger and Maria Artesi and Leonor Palmeira and Nathalie Renotte and Nadine Cambisano and Vinciane Dideberg and Laura Helou and Benoit Charloteaux and Bita Dezfoulian and Gilles Absil and Justine Pêtre and Murielle Sabatiello and Colombine Meunier and W.H. Irwin McLean and Aileen Sandilands and Maeve A. McAleer and Alan D. Irvine and Annette Uwineza and Alice Amani Uwajeni and Sabine Olivier and Keith Durkin and Vincent Bours},
journal = {JID Innovations},
year = {2026},
month = aug,
doi = {10.1016/j.xjidi.2026.100522},
url = {https://doi.org/10.1016/j.xjidi.2026.100522},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Long-read sequencing of
AU - Victor Grentzinger
AU - Maria Artesi
AU - Leonor Palmeira
AU - Nathalie Renotte
AU - Nadine Cambisano
AU - Vinciane Dideberg
AU - Laura Helou
AU - Benoit Charloteaux
AU - Bita Dezfoulian
AU - Gilles Absil
AU - Justine Pêtre
AU - Murielle Sabatiello
AU - Colombine Meunier
AU - W.H. Irwin McLean
AU - Aileen Sandilands
AU - Maeve A. McAleer
AU - Alan D. Irvine
AU - Annette Uwineza
AU - Alice Amani Uwajeni
AU - Sabine Olivier
AU - Keith Durkin
AU - Vincent Bours
PY - 2026
DA - 2026/08/06
JO - JID Innovations
DO - 10.1016/j.xjidi.2026.100522
UR - https://doi.org/10.1016/j.xjidi.2026.100522
AB - Loss-of-function (LOF) variants of the FLG gene are risk factors for atopic dermatitis. However, owing to the repetitive nature of exon 3, these variants are difficult to characterize. We sought to determine whether the use of long-read technologies would enable better characterization of the FLG gene and improve the detection of LOF variants. We sequenced a diverse clinical cohort of 192 samples collected in Belgium, Ireland, and Rwanda using long-read sequencing as well as publicly available data. We identified both common and rare LOF variants linked to atopic dermatitis in our clinical cohort, a number of compound heterozygotes, as well as 1 previously undescribed LOF variant. We also observed 20 previously undescribed FLG alleles, which varied in length by up to 13 kb. These were mostly found in samples of sub-Saharan origin and appear to be products of nonallelic homologous recombination. Despite the use of a long-read–based approach, we did not detect any FLG LOF variants in our African cohort, highlighting differences in FLG LOF burden and atopic dermatitis genetic risk between populations. Our approach has the potential to be a useful tool to identify FLG variants contributing to atopic dermatitis in various human populations.
SN - 2667-0267
ER -