Unbalanced X-chromosome inactivation in haemopoietic cells from normal women

Authors

  • Laura Tonon,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Gaetano Bergamaschi,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Claudia Dellavecchia,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Vittorio Rosti,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Claudia Lucotti,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Lucia Malabarba,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Annunziata Novella,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Elena Vercesi,

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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  • Francesco Frassoni,

    1. BMT Unit, Division of Haematology, Ospedale S. Martino, Genoa, Italy
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  • Mario Cazzola

    1. Department of Internal Medicine and Medical Therapy, Section of Internal Medicine and Medical Oncology, University of Pavia Medical School and IRCCS Policlinico S. Matteo, Pavia, Italy,
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Professor MarioCazzola Internal Medicine and Medical Oncology, Policlinico S. Matteo, 27100 Pavia, Italy.

Abstract

We studied X-chromosome inactivation patterns in blood cells from normal females in three age groups: neonates (umbilical cord blood), 25–32 years old (young women group) and >75 years old (elderly women). Using PCR, the differential allele methylation status was evaluated on active and inactive X chromosomes at the human androgen receptor (HUMARA) and phosphoglycerate kinase (PGK) loci. A cleavage ratio (CR) geqslant R: gt-or-equal, slanted 3.0 was adopted as a cut-off to discriminate between balanced and unbalanced X-chromosome inactivation. In adult women this analysis was also performed on hair bulbs. The frequency of skewed X-inactivation in polymorphonuclear (PMN) cells increased with age: CR geqslant R: gt-or-equal, slanted 3.0 was found in 3/36 cord blood samples, 5/30 young women and 14/31 elderly women. Mathematical analysis of patterns found in neonates indicated that X-chromosome inactivation probably occurs when the total number of haemopoietic stem cell precursors is 14–16. The inactivation patterns found in T lymphocytes were significantly related to those observed in PMNs in both young (P < 0.001) and elderly women (P < 0.01). However, the use of T lymphocytes as a control tissue for distinguishing between skewed inactivation and clonal proliferation proved to be reliable in young females, but not in elderly women, where overestimation of the frequency of clonal myelopoiesis may appear.

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