Unbalanced X-chromosome inactivation in haemopoietic cells from normal women.

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) > or = 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 > or = 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.

journal_name

Br J Haematol

authors

Tonon L,Bergamaschi G,Dellavecchia C,Rosti V,Lucotti C,Malabarba L,Novella A,Vercesi E,Frassoni F,Cazzola M

doi

10.1046/j.1365-2141.1998.00867.x

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

996-1003

issue

4

eissn

0007-1048

issn

1365-2141

journal_volume

102

pub_type

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