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Genetic architecture of band neutrophil fraction in Iceland
The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopa...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160026/ https://www.ncbi.nlm.nih.gov/pubmed/35650273 http://dx.doi.org/10.1038/s42003-022-03462-1 |
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author | Oskarsson, Gudjon R. Magnusson, Magnus K. Oddsson, Asmundur Jensson, Brynjar O. Fridriksdottir, Run Arnadottir, Gudny A. Katrinardottir, Hildigunnur Rognvaldsson, Solvi Halldorsson, Gisli H. Sveinbjornsson, Gardar Ivarsdottir, Erna V. Stefansdottir, Lilja Ferkingstad, Egil Norland, Kristjan Tragante, Vinicius Saemundsdottir, Jona Jonasdottir, Aslaug Jonasdottir, Adalbjorg Sigurjonsdottir, Svanhvit Petursdottir, Karen O. Davidsson, Olafur B. Rafnar, Thorunn Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Vidarsson, Brynjar Sigurdardottir, Olof Masson, Gisli Gudbjartsson, Daniel F. Jonsdottir, Ingileif Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari |
author_facet | Oskarsson, Gudjon R. Magnusson, Magnus K. Oddsson, Asmundur Jensson, Brynjar O. Fridriksdottir, Run Arnadottir, Gudny A. Katrinardottir, Hildigunnur Rognvaldsson, Solvi Halldorsson, Gisli H. Sveinbjornsson, Gardar Ivarsdottir, Erna V. Stefansdottir, Lilja Ferkingstad, Egil Norland, Kristjan Tragante, Vinicius Saemundsdottir, Jona Jonasdottir, Aslaug Jonasdottir, Adalbjorg Sigurjonsdottir, Svanhvit Petursdottir, Karen O. Davidsson, Olafur B. Rafnar, Thorunn Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Vidarsson, Brynjar Sigurdardottir, Olof Masson, Gisli Gudbjartsson, Daniel F. Jonsdottir, Ingileif Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari |
author_sort | Oskarsson, Gudjon R. |
collection | PubMed |
description | The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopathies like Pelger-Huët anomaly. To search for sequence variants affecting nuclear morphology of granulocytes, we performed a genome-wide association study using band neutrophil fraction from 88,101 Icelanders. We describe 13 sequence variants affecting band neutrophil fraction at nine loci. Five of the variants are at the Lamin B receptor (LBR) locus, encoding an inner nuclear membrane protein. Mutations in LBR are linked to Pelger-Huët anomaly. In addition, we identify cosegregation of a rare stop-gain sequence variant in LBR and Pelger Huët anomaly in an Icelandic eight generation pedigree, initially reported in 1963. Two of the other loci include genes which, like LBR, play a role in the nuclear membrane function and integrity. These GWAS results highlight the role proteins of the inner nuclear membrane have as important for neutrophil nuclear morphology. |
format | Online Article Text |
id | pubmed-9160026 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-91600262022-06-03 Genetic architecture of band neutrophil fraction in Iceland Oskarsson, Gudjon R. Magnusson, Magnus K. Oddsson, Asmundur Jensson, Brynjar O. Fridriksdottir, Run Arnadottir, Gudny A. Katrinardottir, Hildigunnur Rognvaldsson, Solvi Halldorsson, Gisli H. Sveinbjornsson, Gardar Ivarsdottir, Erna V. Stefansdottir, Lilja Ferkingstad, Egil Norland, Kristjan Tragante, Vinicius Saemundsdottir, Jona Jonasdottir, Aslaug Jonasdottir, Adalbjorg Sigurjonsdottir, Svanhvit Petursdottir, Karen O. Davidsson, Olafur B. Rafnar, Thorunn Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Vidarsson, Brynjar Sigurdardottir, Olof Masson, Gisli Gudbjartsson, Daniel F. Jonsdottir, Ingileif Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Commun Biol Article The characteristic lobulated nuclear morphology of granulocytes is partially determined by composition of nuclear envelope proteins. Abnormal nuclear morphology is primarily observed as an increased number of hypolobulated immature neutrophils, called band cells, during infection or in rare envelopathies like Pelger-Huët anomaly. To search for sequence variants affecting nuclear morphology of granulocytes, we performed a genome-wide association study using band neutrophil fraction from 88,101 Icelanders. We describe 13 sequence variants affecting band neutrophil fraction at nine loci. Five of the variants are at the Lamin B receptor (LBR) locus, encoding an inner nuclear membrane protein. Mutations in LBR are linked to Pelger-Huët anomaly. In addition, we identify cosegregation of a rare stop-gain sequence variant in LBR and Pelger Huët anomaly in an Icelandic eight generation pedigree, initially reported in 1963. Two of the other loci include genes which, like LBR, play a role in the nuclear membrane function and integrity. These GWAS results highlight the role proteins of the inner nuclear membrane have as important for neutrophil nuclear morphology. Nature Publishing Group UK 2022-06-01 /pmc/articles/PMC9160026/ /pubmed/35650273 http://dx.doi.org/10.1038/s42003-022-03462-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Oskarsson, Gudjon R. Magnusson, Magnus K. Oddsson, Asmundur Jensson, Brynjar O. Fridriksdottir, Run Arnadottir, Gudny A. Katrinardottir, Hildigunnur Rognvaldsson, Solvi Halldorsson, Gisli H. Sveinbjornsson, Gardar Ivarsdottir, Erna V. Stefansdottir, Lilja Ferkingstad, Egil Norland, Kristjan Tragante, Vinicius Saemundsdottir, Jona Jonasdottir, Aslaug Jonasdottir, Adalbjorg Sigurjonsdottir, Svanhvit Petursdottir, Karen O. Davidsson, Olafur B. Rafnar, Thorunn Holm, Hilma Olafsson, Isleifur Onundarson, Pall T. Vidarsson, Brynjar Sigurdardottir, Olof Masson, Gisli Gudbjartsson, Daniel F. Jonsdottir, Ingileif Norddahl, Gudmundur L. Thorsteinsdottir, Unnur Sulem, Patrick Stefansson, Kari Genetic architecture of band neutrophil fraction in Iceland |
title | Genetic architecture of band neutrophil fraction in Iceland |
title_full | Genetic architecture of band neutrophil fraction in Iceland |
title_fullStr | Genetic architecture of band neutrophil fraction in Iceland |
title_full_unstemmed | Genetic architecture of band neutrophil fraction in Iceland |
title_short | Genetic architecture of band neutrophil fraction in Iceland |
title_sort | genetic architecture of band neutrophil fraction in iceland |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9160026/ https://www.ncbi.nlm.nih.gov/pubmed/35650273 http://dx.doi.org/10.1038/s42003-022-03462-1 |
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