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Estimation of mutation rate at human glycophorin A locus in hematopoietic stem cell progenitors
Author(s) -
Vickers M. A.,
Hoy T.,
Lake H.,
Kyoizumi S.,
Boyse J.,
Hewitt M.
Publication year - 2002
Publication title -
environmental and molecular mutagenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 87
eISSN - 1098-2280
pISSN - 0893-6692
DOI - 10.1002/em.10076
Subject(s) - glycophorin , mutant , stem cell , mutation rate , biology , genetics , population , locus (genetics) , progenitor cell , hematopoietic stem cell , mutation , haematopoiesis , cell division , cell , gene , antigen , sociology , demography
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 × 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 detect in surveys because their distribution within the general population is so skewed. Environ. Mol. Mutagen. 39:333–341, 2002. © 2002 Wiley‐Liss, Inc.