General Biological Aspects of Oncogenesis
Pimentel Enrique in Oncogenes, 2020
The X sex chromatin, also called Barr body, may be observed in more than 30% of the interphase nuclei of most cells containing two or more X chromosomes and consequently, in mammals it is found only in somatic cells of the female. In general, the number of Barr bodies in a given cell is equal to the number of X chromosomes minus one, the latter corresponding to the actively transcribing X chromosome. The inactivation of X chromosomes to form Barr bodies is apparently associated with a process of hypermethylation of DNA sequences,17 which determines an almost complete transcriptional silence of the whole X chromosome. Barr bodies are difficult to visualize in neoplastic cells due to the aforementioned increase in the heterochromatin fraction and other morphological changes occurring in the nucleus, but there is evidence that their number and/or structure may be abnormal at least in some types of cancer cells whereas no changes are observed in benign tumors.18,20 However, no correlation exists between the incidence of Barr bodies in malignant tumors and different prognostic factors like the spread and histological grading of the tumor.21 The measurement of X-linked enzymatic activities in female teratocarcinoma cells, which are malignant cells containing two X chromosomes, give conflictive results as to whether only one or both X chromosomes are active in the tumor cells.22,23
Patterns of Inheritance: Mendelian and Non-Mendelian
Merlin G. Butler, F. John Meaney in Genetics of Developmental Disabilities, 2019
Although males have only one copy of an X-linked gene and females have two copies, males and females generally have equal amounts of the proteins encoded for by these genes. In the 1960s, Dr. Mary Lyon proposed a mechanism to explain this “dosage compensation.” This principle is known as X inactivation or the “Lyon” hypothesis. This hypothesis states that in females only one X chromosome in each somatic cell is active although recent evidence indicates that part of the inactive X chromosome remains active (2). The other X chromosome is inactivated and appears in interphase cells as a condensed sex chromatin or the “Barr body.” Inactivation occurs in the first week of embryonic development. The inactivation process is random with either the paternal or maternal X inactivated. Once an X chromosome is inactivated in a cell, all of the descendents of that cell will have the same inactive X. Therefore, X inactivation is randomly determined but fixed for all future cells. As a result of X inactivation, females have two populations of cells. One population has an active paternal X chromosome and the other has an active maternal X chromosome. Females are “mosaics” for the X chromosome with two populations of cells. Males are not mosaics but are “hemizygous.” They have only one X chromosome in each cell and that X remains active.
Genetic counselling in Mendelian disorders
Angus Clarke, Alex Murray, Julian Sampson in Harper's Practical Genetic Counselling, 2019
The terms ‘dominant’ and ‘recessive’ must be used with caution in X-linked disease, because a high degree of variability is seen in disease expression in the heterozygous female. The factors that lead to a heterozygous variant of an autosomal gene manifesting in the phenotype – that is, that make it dominant or recessive – may still apply to loci on the X chromosome but, in addition, there are also the effects of the random nature of X-chromosome inactivation (Mary Lyon's hypothesis). This process applies to a large majority of the loci on the X chromosome in the human female. One of the two X chromosomes is randomly inactivated in each cell in the early embryo and becomes visible cytogenetically as the ‘sex chromatin’ or ‘Barr body’ under the nuclear membrane. Because the clonal descendants of each cell retain the same inactivated X chromosome, it follows that a female heterozygous for an X-linked disorder or trait will be mosaic, with two populations of cells, one of which has the ‘normal’ and the other the ‘abnormal’ X chromosome functioning.
Review of Ilana Löwy, Imperfect Pregnancies: A History of Birth Defects & Prenatal Diagnosis
Published in The American Journal of Bioethics, 2019
Chapter 5 traces the history of the sex chromosome aneuploidies Turner and Klinefelter syndromes. Prior to the correlation of these syndromes with aneuploidy of the sex chromosomes, they were assumed to be conditions of sex inversion, with individuals with Klinefelter syndrome presumed to be biological women (due to Barr body presence) and individuals with Turner syndrome biological men (due to Barr body absence). Women receiving amniocentesis to diagnose Down, Edwards, or Patau syndromes in the 1960s were sometimes confronted with the diagnosis of a sex chromosome aneuploidy, diagnoses for which little data existed on the outcomes of children with these conditions. The remainder of the chapter discusses modern detection and understanding of these syndromes, including the differences between the current state of prenatal detection of the two conditions (i.e., Turner syndrome is often diagnosed via ultrasound; Klinefelter syndrome as an incidental finding in the evaluation of Down syndrome risk).
Related Knowledge Centers
- Interphase
- Karyotype
- Ploidy
- X Chromosome
- Embryo
- Neutrophil
- Genotype
- Cell Nucleus
- Xy Sex-Determination System
- X-Inactivation