The PIG-A gene mutation assay in human biomonitoring and disease

Lawrence, Rachel; Munn, Kathryn; Naser, Hamsa; Thomas, Laura; Haboubi, Hasan; Williams, Lisa; Doak, Shareen; Jenkins, Gareth

doi:10.1002/em.22577

Journal article 401 views 69 downloads

The PIG-A gene mutation assay in human biomonitoring and disease

Rachel Lawrence

, Kathryn Munn, Hamsa Naser, Laura Thomas

, Hasan Haboubi, Lisa Williams, Shareen Doak

, Gareth Jenkins

Environmental and Molecular Mutagenesis, Volume: 64, Issue: 8-9, Pages: 480 - 493

Swansea University Authors: Kathryn Munn, Hamsa Naser, Laura Thomas , Shareen Doak , Gareth Jenkins

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DOI (Published version): 10.1002/em.22577

Abstract

The blood cell phosphatidylinositol glycan class A (PIG-A) gene mutation assay has been extensively researched in rodents for in vivo mutagenicity testing and is now being investigated in humans. The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation...

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Published in:	Environmental and Molecular Mutagenesis
ISSN:	0893-6692 1098-2280
Published:	Wiley 2023
Online Access:	Check full text
URI:	https://cronfa.swan.ac.uk/Record/cronfa65085
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first_indexed	2023-11-24T10:11:55Z
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The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation in this X-linked gene can lead to loss of membrane-bound GPI anchors, which can be enumerated via corresponding GPI-anchored proteins (e.g., CD55) using flow cytometry. The studies published to date by different research groups demonstrate a remarkable consistency in PIG-A mutant frequencies. Moreover, with the low background level of mutant erythrocytes in healthy subjects (2.9–5.56 × 10−6 mutants), induction of mutation post genotoxic exposure can be detected. Cigarette smoking, radiotherapy, and occupational exposures, including lead, have been shown to increase mutant levels. Future applications of this test include identifying new harmful agents and establishing new exposure limits. This mutational monitoring approach may also identify individuals at higher risk of cancer development. In addition, identifying protective agents that could mitigate these effects may reduce baseline somatic mutation levels and such behaviors can be encouraged. Further technological progress is required including establishing underlying mechanisms of GPI anchor loss, protocol standardization, and the development of cryopreservation methods to improve GPI-anchor stability over time. If successful, this assay has the potential be widely employed, for example, in rural and low-income countries. 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spelling	v2 65085 2023-11-24 The PIG-A gene mutation assay in human biomonitoring and disease 8575c068395b3939a2fafa7ae6eee4a0 Kathryn Munn Kathryn Munn true false e64b4076dc561ffb4432bdf65752346a Hamsa Naser Hamsa Naser true false 6f80a1638d852bd88d37afe3aeb2fb62 0000-0002-8621-5285 Laura Thomas Laura Thomas true false 8f70286908f67238a527a98cbf66d387 0000-0002-6753-1987 Shareen Doak Shareen Doak true false a44095d26187304e903da7ca778697b6 0000-0002-5437-8389 Gareth Jenkins Gareth Jenkins true false 2023-11-24 The blood cell phosphatidylinositol glycan class A (PIG-A) gene mutation assay has been extensively researched in rodents for in vivo mutagenicity testing and is now being investigated in humans. The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation in this X-linked gene can lead to loss of membrane-bound GPI anchors, which can be enumerated via corresponding GPI-anchored proteins (e.g., CD55) using flow cytometry. The studies published to date by different research groups demonstrate a remarkable consistency in PIG-A mutant frequencies. Moreover, with the low background level of mutant erythrocytes in healthy subjects (2.9–5.56 × 10−6 mutants), induction of mutation post genotoxic exposure can be detected. Cigarette smoking, radiotherapy, and occupational exposures, including lead, have been shown to increase mutant levels. Future applications of this test include identifying new harmful agents and establishing new exposure limits. This mutational monitoring approach may also identify individuals at higher risk of cancer development. In addition, identifying protective agents that could mitigate these effects may reduce baseline somatic mutation levels and such behaviors can be encouraged. Further technological progress is required including establishing underlying mechanisms of GPI anchor loss, protocol standardization, and the development of cryopreservation methods to improve GPI-anchor stability over time. If successful, this assay has the potential be widely employed, for example, in rural and low-income countries. Here, we review the current literature on PIG-A mutation in humans and discuss the potential role of this assay in human biomonitoring and disease detection. Journal Article Environmental and Molecular Mutagenesis 64 8-9 480 493 Wiley 0893-6692 1098-2280 Biomonitoring, cancer, environmental exposures, mutation, occupational health 15 12 2023 2023-12-15 10.1002/em.22577 COLLEGE NANME COLLEGE CODE Swansea University SU Library paid the OA fee (TA Institutional Deal) Swansea University 2024-03-08T11:02:47.6352354 2023-11-24T10:03:51.0995125 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Rachel Lawrence 0000-0002-1023-5220 1 Kathryn Munn 2 Hamsa Naser 3 Laura Thomas 0000-0002-8621-5285 4 Hasan Haboubi 5 Lisa Williams 6 Shareen Doak 0000-0002-6753-1987 7 Gareth Jenkins 0000-0002-5437-8389 8 65085__29100__6e69b419d7324700952771d8fa56bb51.pdf 65085.VOR.pdf 2023-11-24T10:12:52.9661936 Output 3603595 application/pdf Version of Record true © 2023 The Authors. Environmental and Molecular Mutagenesis published by Wiley Periodicals LLC on behalf of Environmental Mutagenesis and Genomics Society. Distributed under the terms of a Creative Commons Attribution Non Commercial 4.0 License (CC BY-NC 4.0). true eng https://creativecommons.org/licenses/by-nc/4.0/
title	The PIG-A gene mutation assay in human biomonitoring and disease
spellingShingle	The PIG-A gene mutation assay in human biomonitoring and disease Kathryn Munn Hamsa Naser Laura Thomas Shareen Doak Gareth Jenkins
title_short	The PIG-A gene mutation assay in human biomonitoring and disease
title_full	The PIG-A gene mutation assay in human biomonitoring and disease
title_fullStr	The PIG-A gene mutation assay in human biomonitoring and disease
title_full_unstemmed	The PIG-A gene mutation assay in human biomonitoring and disease
title_sort	The PIG-A gene mutation assay in human biomonitoring and disease
author_id_str_mv	8575c068395b3939a2fafa7ae6eee4a0 e64b4076dc561ffb4432bdf65752346a 6f80a1638d852bd88d37afe3aeb2fb62 8f70286908f67238a527a98cbf66d387 a44095d26187304e903da7ca778697b6
author_id_fullname_str_mv	8575c068395b3939a2fafa7ae6eee4a0_*_Kathryn Munn e64b4076dc561ffb4432bdf65752346a__Hamsa Naser 6f80a1638d852bd88d37afe3aeb2fb62__Laura Thomas 8f70286908f67238a527a98cbf66d387__Shareen Doak a44095d26187304e903da7ca778697b6_**_Gareth Jenkins
author	Kathryn Munn Hamsa Naser Laura Thomas Shareen Doak Gareth Jenkins
author2	Rachel Lawrence Kathryn Munn Hamsa Naser Laura Thomas Hasan Haboubi Lisa Williams Shareen Doak Gareth Jenkins
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container_title	Environmental and Molecular Mutagenesis
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doi_str_mv	10.1002/em.22577
publisher	Wiley
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description	The blood cell phosphatidylinositol glycan class A (PIG-A) gene mutation assay has been extensively researched in rodents for in vivo mutagenicity testing and is now being investigated in humans. The PIG-A gene is involved in glycosyl phosphatidylinositol (GPI)-anchor biosynthesis. A single mutation in this X-linked gene can lead to loss of membrane-bound GPI anchors, which can be enumerated via corresponding GPI-anchored proteins (e.g., CD55) using flow cytometry. The studies published to date by different research groups demonstrate a remarkable consistency in PIG-A mutant frequencies. Moreover, with the low background level of mutant erythrocytes in healthy subjects (2.9–5.56 × 10−6 mutants), induction of mutation post genotoxic exposure can be detected. Cigarette smoking, radiotherapy, and occupational exposures, including lead, have been shown to increase mutant levels. Future applications of this test include identifying new harmful agents and establishing new exposure limits. This mutational monitoring approach may also identify individuals at higher risk of cancer development. In addition, identifying protective agents that could mitigate these effects may reduce baseline somatic mutation levels and such behaviors can be encouraged. Further technological progress is required including establishing underlying mechanisms of GPI anchor loss, protocol standardization, and the development of cryopreservation methods to improve GPI-anchor stability over time. If successful, this assay has the potential be widely employed, for example, in rural and low-income countries. Here, we review the current literature on PIG-A mutation in humans and discuss the potential role of this assay in human biomonitoring and disease detection.
published_date	2023-12-15T11:02:46Z
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The PIG-A gene mutation assay in human biomonitoring and disease

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