Estimation of mutation rate at human glycophorin A locus in hematopoietic stem cell progenitors

Mark Adrian Vickers, T. Hoy, S. Kyoizumi, M. Hewitt, H. Lake, J. Boyse

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Surveys of human mutant cells exhibit a few individuals with relatively high "outlying" values, which might be explained by rare mutations occurring during development. To estimate how commonly this occurs, mutant red cell frequencies at the glycophorin A locus in 135 neonates and 109 children and adolescents from three research centers are compared with simulations in which mutations arise from successive cycles of binary fission. The simulations predict the data most accurately when the mutation rate in stem cell precursors is about 2-4 x 10(-7) per division cycle, which is similar to previous estimates from adult stem cell divisions. If these mutation rates are accurate, and the number of stem cell divisions during adult life is as low as previously estimated, it is predicted that up to one-sixth of mutant stem cells over a lifetime arose in early life. However, these mutant stem cells would be difficult to defect in surveys because their distribution within the general population is so skewed. (C) 2002 Wiley-Liss, Inc.

Original languageEnglish
Pages (from-to)333-341
Number of pages8
JournalEnvironmental and Molecular Mutagenesis
Volume39
Issue number4
DOIs
Publication statusPublished - 2002

Keywords

  • mutation
  • glycophorin A
  • stem cells
  • childhood
  • mutation rate
  • VIVO SOMATIC MUTATION
  • HUMAN COLORECTAL-CARCINOMA
  • UMBILICAL-CORD BLOOD
  • IN-VIVO
  • A LOCUS
  • HUMAN-LYMPHOCYTES
  • INVIVO MUTATIONS
  • PERIPHERAL-BLOOD
  • BONE-MARROW
  • ASSAY

Cite this

Estimation of mutation rate at human glycophorin A locus in hematopoietic stem cell progenitors. / Vickers, Mark Adrian; Hoy, T.; Kyoizumi, S.; Hewitt, M.; Lake, H.; Boyse, J.

In: Environmental and Molecular Mutagenesis, Vol. 39, No. 4, 2002, p. 333-341.

Research output: Contribution to journalArticle

Vickers, Mark Adrian ; Hoy, T. ; Kyoizumi, S. ; Hewitt, M. ; Lake, H. ; Boyse, J. / Estimation of mutation rate at human glycophorin A locus in hematopoietic stem cell progenitors. In: Environmental and Molecular Mutagenesis. 2002 ; Vol. 39, No. 4. pp. 333-341.
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AU - Lake, H.

AU - Boyse, J.

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AB - Surveys of human mutant cells exhibit a few individuals with relatively high "outlying" values, which might be explained by rare mutations occurring during development. To estimate how commonly this occurs, mutant red cell frequencies at the glycophorin A locus in 135 neonates and 109 children and adolescents from three research centers are compared with simulations in which mutations arise from successive cycles of binary fission. The simulations predict the data most accurately when the mutation rate in stem cell precursors is about 2-4 x 10(-7) per division cycle, which is similar to previous estimates from adult stem cell divisions. If these mutation rates are accurate, and the number of stem cell divisions during adult life is as low as previously estimated, it is predicted that up to one-sixth of mutant stem cells over a lifetime arose in early life. However, these mutant stem cells would be difficult to defect in surveys because their distribution within the general population is so skewed. (C) 2002 Wiley-Liss, Inc.

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KW - UMBILICAL-CORD BLOOD

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KW - INVIVO MUTATIONS

KW - PERIPHERAL-BLOOD

KW - BONE-MARROW

KW - ASSAY

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JO - Environmental and Molecular Mutagenesis

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