Lack of X inactivation associated with maternal X isodisomy: evidence for a counting mechanism prior to X inactivation during human embryogenesis
| Autor: | Migeon, B. R., Jeppesen, P., Torchia, B. S., Fu, S., Dunn, M. A., Axelman, J., Schmeckpeper, B. J., Fantes, J., Zori, R. T., Driscoll, D. J. |
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| Jazyk: | angličtina |
| Rok vydání: | 1996 |
| Předmět: |
DNA Replication
Genetic Markers Male Ploidies X Chromosome Transcription Genetic Mosaicism Chromosome Mapping Turner Syndrome Hybrid Cells Polymerase Chain Reaction Embryonic and Fetal Development Pregnancy Karyotyping Humans Female Chromosome Deletion Child Cell Division Cells Cultured In Situ Hybridization Fluorescence Sex Chromosome Aberrations Research Article |
| Popis: | We have previously reported functional disomy for X-linked genes in females with tiny ring X chromosomes and a phenotype significantly more abnormal than Turner syndrome. In such cases the disomy results from failure of these X chromosomes to inactivate because they lack DNA sequences essential for cis X inactivation. Here we describe a novel molecular mechanism for functional X disomy that is associated with maternal isodisomy. In this case, the severe mental retardation and multiple congenital abnormalities in a female with a mosaic 45,X/ 46,X,del(X)(q21.3-qter)/ 46X,r(X) karyotype are associated with overexpression of the genes within Xpter to Xq21.31 in many of her cells. Her normal X, ring X, and deleted linear X chromosomes originate from the same maternal X chromosome, and all are transcriptionally active. None expresses X inactive specific transcript (XIST), although the locus and region of the putative X inactivation center (XIC) are present on both normal and linear deleted X chromosomes. To our knowledge, this is the first report of a functional maternal X isodisomy, and the largest X chromosome to escape inactivation. In addition, these results (1) show that cis inactivation does not invariably occur in human females with two X chromosomes, even when the XIC region is present on both of them; (2) provide evidence for a critical time prior to the visible onset of X inactivation in the embryo when decisions about X inactivation are made; and (3) support the hypothesis that the X chromosome counting mechanism involves chromosomal imprinting, occurs prior to the onset of random inactivation, and is required for subsequent inactivation of the chromosome. |
| Databáze: | OpenAIRE |
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