X‐chromosome Inactivation and Disease

Mary F Lyon, Medical Research Council Mammalian Genetics Unit, Harwell, UK

Published online: July 2007

DOI: 10.1002/9780470015902.a0005480.pub2

X-chromosome inactivation is the phenomenon in which one of the two X chromosomes in every somatic cell of female mammals becomes transcriptionally inactive early in embryonic development. This has the result of equalizing the effective gene dosage of X-linked genes in chromosomally XX females and XY males, and is hence known as a dosage-compensation mechanism. In humans, X-chromosome inactivation has implications for the effects seen in diseases due either to X-linked genes or to numerical or structural anomalies of the X-chromosome.

Keywords: X-linked diseases; X-chromosome aneuploidy; X-autosome translocations; XIST gene; X-inactivation centre

 References
    Amos-Landgraf JM, Cottle A, Plenge RM et al. (2006) X-chromosome inactivation patterns of 1005 phenotypically unaffected females. American Journal of Human Genetics 79: 493–499.
    Carrel L and Willard HF (2005) X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature 434: 400–404.
    Chitnis S, Derom C, Vlietinck R et al. (1999) X Chromosome-inactivation patterns confirm the late timing of monoamniotic-MZ twinning. American Journal of Human Genetics 65: 570–571.
    Lee JT and Lu N (1999) Targeted mutagenesis of Tsix leads to nonrandom X inactivation. Cell 99: 47–57.
    Migeon BR, Chowdhury AS, Dunston JA and McIntosh I (2001) Identification of TSIX encoding an RNA antisense to human XIST reveals differences from its murine counterpart: Implications for X-inactivation. American Journal of Human Genetics 69: 951–960.
    Migeon BR, Luo S, Jani M and Jeppesen P (1994) The severe phenotype of females with tiny ring X chromosomes is associated with inability of these chromosomes to undergo X inactivation. American Journal of Human Genetics 55: 497–504.
    Naumova AK, Plenge RM, Bird LM et al. (1996) Heritability of X chromosome inactivation phenotype in a large family. American Journal of Human Genetics 58: 1111–1119.
    Okamoto I, Otte AP, Allis D et al. (2004) Epigenetic dynamics of imprinted X inactivation during early mouse development. Science 303: 644–648.
    Pegoraro E, Whitaker J, Mowery-Rushton P et al. (1997) Familial skewed X inactivation: a molecular trait associated with high spontaneous abortion rate maps to Xq28. American Journal of Human Genetics 61: 160–170.
    Plenge RM, Hendrich BD, Schwartz C et al. (1997) A promoter mutation in the XIST gene in two unrelated families with skewed X-chromosome inactivation. Nature Genetics 17: 353–356.
    Plenge RM, Stevenson RA, Lubs HA et al. (2002) Skewed X-chromosome inactivation is a common feature of X-linked mental retardation disorders. American Journal of Human Genetics 71: 168–173.
    Ross JL, Roeltgen D, Kushner H et al. (2000) The Turner syndrome-associated neurocognitive phenotype maps to distal Xp. American Journal of Human Genetics 67: 672–681.
    Schmidt M and Du Sart D (1992) Functional disomies of the X chromosome influence the cell selection and hence the X inactivation pattern in females with balanced X-autosome translocations: a review of 122 cases. American Journal of Medical Genetics 42: 161–169.
    Talebizadeh Z, Simon SD and Butler MG (2006) X chromosome gene expression in human tissues: male and female comparisons. Genomics 88: 675–681.
    White WM, Willard HF, Van Dyke DL and Wolfe DJ (1998) The spreading of X inactivation into autosome material of an X-autosome translocation: evidence for a difference between autosomal and X-chromosomal DNA. American Journal of Human Genetics 63: 20–28.
    Wutz A and Jaenisch R (2000) A shift from reversible to irreversible X inactivation is triggered during ES cell differentiation. Molecular Cell 5: 695–705.
 Further Reading
    Avner P and Heard E (2001) X- chromosome inactivation: counting, choice and initiation. Nature Reviews Genetics 2: 58–67.
    Belmont JW (1996) Genetic control of X inactivation and processes leading to X inactivation skewing. American Journal of Human Genetics 58: 1101–1108.
    Disteche CM (1995) Escape from X inactivation in human and mouse. Trends in Genetics 11: 17–22.
    Heard E (2005) Delving into the diversity of facultative heterochromatin: the epigenetics of the inactive X chromosome. Current Opinion in Genetics and Development 15: 482–489.
    Lucchesi SI, Kelly WG and Panning B (2005) Chromatin remodeling in dosage compensation. Annual Review of Genetics 39: 615–651.
    Lyon MF (1988) Clones & X-chromosomes. Journal of Pathology 155: 97–99.
    Migeon BR (1994) X-chromosome inactivation: molecular mechanisms and genetic consequences. Trends in Genetics 10: 230–235.
    Plath K, Mlynarczyil-Evans S, Nusinow DA and Panning B (2002) XIST RNA and the mechanism of X-chromosome inactivation. Annual Review of Genetics 36: 233–278.

Related Sub-Topics:

Genes, Molecules and Cellular Processes | Developmental Disorders | Genomic Disorders | Epigenetics and Disease | Chromosomes and Chromatin Modifications
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Article Title: X‐chromosome Inactivation and Disease
 
How to Cite close
Lyon, Mary F(Jul 2007) X‐chromosome Inactivation and Disease. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005480.pub2]