Analysis of loss of inactive X chromosomes in interphase cells.
We have developed a method that allows, for the first time, a specific analysis of the inactive X chromosome (Xi) in interphase cells. By combining immunolabeling of acetylated histone H4 with specific antisera and FISH with an X-chromosome centromere-specific DNA probe, micronucleated whole Xis in human female cells may be identified by their lack of histone H4 acetylation. As one example of the potential applications of this methodology in genetic studies in humans, an artifact-free X-chromosome aneuploidy detection in lymphocytes of women of different ages has been performed. Our results indicate that not only the Xi but also the active X chromosome is preferentially lost during aging, indicating that the high frequency of sex-chromosome aneuploidy in human females cannot be explained solely by a lack of negative selection of Xi aneuploid cells. Further applications of the proposed methodology in genetic studies are discussed.
MGC--Department of Radiation Genetics and Chemical Mutagenesis, Leiden University. surralles@rullf2.leidenuniv.nl
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Surrallés
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Jeppesen
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Morrison
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Natarajan
D000328:Adult; D000375:Aging / Q000235:genetics*; D000782:Aneuploidy; D005260:Female; D006801:Humans; D007399:Interphase / Q000235:genetics*; D008875:Middle Aged; D014960:X Chromosome