Cargando…
A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism
The FCGR3A gene encodes for the receptor important for antibody-dependent natural killer cell-mediated cytotoxicity. FCGR3A gene polymorphisms could affect the success of monoclonal antibody therapy. Although polymorphisms, such as the FcγRIIIA-V158F and -48L/R/H, have been studied extensively, an o...
Autores principales: | , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206037/ https://www.ncbi.nlm.nih.gov/pubmed/30374078 http://dx.doi.org/10.1038/s41598-018-34258-1 |
_version_ | 1783366286006288384 |
---|---|
author | Mahaweni, Niken M. Olieslagers, Timo I. Rivas, Ivan Olivares Molenbroeck, Stefan J. J. Groeneweg, Mathijs Bos, Gerard M. J. Tilanus, Marcel G. J. Voorter, Christina E. M. Wieten, Lotte |
author_facet | Mahaweni, Niken M. Olieslagers, Timo I. Rivas, Ivan Olivares Molenbroeck, Stefan J. J. Groeneweg, Mathijs Bos, Gerard M. J. Tilanus, Marcel G. J. Voorter, Christina E. M. Wieten, Lotte |
author_sort | Mahaweni, Niken M. |
collection | PubMed |
description | The FCGR3A gene encodes for the receptor important for antibody-dependent natural killer cell-mediated cytotoxicity. FCGR3A gene polymorphisms could affect the success of monoclonal antibody therapy. Although polymorphisms, such as the FcγRIIIA-V158F and -48L/R/H, have been studied extensively, an overview of other polymorphisms within this gene is lacking. To provide an overview of FCGR3A polymorphisms, we analysed the 1000 Genomes project database and found a total of 234 polymorphisms within the FCGR3A gene, of which 69%, 16%, and 15% occur in the intron, UTR, and exon regions respectively. Additionally, only 16% of all polymorphisms had a minor allele frequency (MAF) > 0.01. To facilitate (full-length) analysis of FCGR3A gene polymorphism, we developed a FCGR3A gene-specific amplification and sequencing protocol for Sanger sequencing and MinION (Nanopore Technologies). First, we used the Sanger sequencing protocol to study the presence of the V158F polymorphism in 76 individuals resulting in frequencies of 38% homozygous T/T, 7% homozygous G/G and 55% heterozygous. Next, we performed a pilot with both Sanger sequencing and MinION based sequencing of 14 DNA samples which showed a good concordance between Sanger- and MinION sequencing. Additionally, we detected 13 SNPs listed in the 1000 Genome Project, from which 11 had MAF > 0.01, and 10 SNPs were not listed in 1000 Genome Project. In summary, we demonstrated that FCGR3A gene is more polymorphic than previously described. As most novel polymorphisms are located in non-coding regions, their functional relevance needs to be studied in future functional studies. |
format | Online Article Text |
id | pubmed-6206037 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-62060372018-11-01 A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism Mahaweni, Niken M. Olieslagers, Timo I. Rivas, Ivan Olivares Molenbroeck, Stefan J. J. Groeneweg, Mathijs Bos, Gerard M. J. Tilanus, Marcel G. J. Voorter, Christina E. M. Wieten, Lotte Sci Rep Article The FCGR3A gene encodes for the receptor important for antibody-dependent natural killer cell-mediated cytotoxicity. FCGR3A gene polymorphisms could affect the success of monoclonal antibody therapy. Although polymorphisms, such as the FcγRIIIA-V158F and -48L/R/H, have been studied extensively, an overview of other polymorphisms within this gene is lacking. To provide an overview of FCGR3A polymorphisms, we analysed the 1000 Genomes project database and found a total of 234 polymorphisms within the FCGR3A gene, of which 69%, 16%, and 15% occur in the intron, UTR, and exon regions respectively. Additionally, only 16% of all polymorphisms had a minor allele frequency (MAF) > 0.01. To facilitate (full-length) analysis of FCGR3A gene polymorphism, we developed a FCGR3A gene-specific amplification and sequencing protocol for Sanger sequencing and MinION (Nanopore Technologies). First, we used the Sanger sequencing protocol to study the presence of the V158F polymorphism in 76 individuals resulting in frequencies of 38% homozygous T/T, 7% homozygous G/G and 55% heterozygous. Next, we performed a pilot with both Sanger sequencing and MinION based sequencing of 14 DNA samples which showed a good concordance between Sanger- and MinION sequencing. Additionally, we detected 13 SNPs listed in the 1000 Genome Project, from which 11 had MAF > 0.01, and 10 SNPs were not listed in 1000 Genome Project. In summary, we demonstrated that FCGR3A gene is more polymorphic than previously described. As most novel polymorphisms are located in non-coding regions, their functional relevance needs to be studied in future functional studies. Nature Publishing Group UK 2018-10-29 /pmc/articles/PMC6206037/ /pubmed/30374078 http://dx.doi.org/10.1038/s41598-018-34258-1 Text en © The Author(s) 2018 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/. |
spellingShingle | Article Mahaweni, Niken M. Olieslagers, Timo I. Rivas, Ivan Olivares Molenbroeck, Stefan J. J. Groeneweg, Mathijs Bos, Gerard M. J. Tilanus, Marcel G. J. Voorter, Christina E. M. Wieten, Lotte A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism |
title | A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism |
title_full | A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism |
title_fullStr | A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism |
title_full_unstemmed | A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism |
title_short | A comprehensive overview of FCGR3A gene variability by full-length gene sequencing including the identification of V158F polymorphism |
title_sort | comprehensive overview of fcgr3a gene variability by full-length gene sequencing including the identification of v158f polymorphism |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6206037/ https://www.ncbi.nlm.nih.gov/pubmed/30374078 http://dx.doi.org/10.1038/s41598-018-34258-1 |
work_keys_str_mv | AT mahaweninikenm acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT olieslagerstimoi acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT rivasivanolivares acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT molenbroeckstefanjj acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT groenewegmathijs acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT bosgerardmj acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT tilanusmarcelgj acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT voorterchristinaem acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT wietenlotte acomprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT mahaweninikenm comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT olieslagerstimoi comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT rivasivanolivares comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT molenbroeckstefanjj comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT groenewegmathijs comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT bosgerardmj comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT tilanusmarcelgj comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT voorterchristinaem comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism AT wietenlotte comprehensiveoverviewoffcgr3agenevariabilitybyfulllengthgenesequencingincludingtheidentificationofv158fpolymorphism |