The word mosaic is a form of work of art in which pictures are produced joining together minutes pieces of glass, stones and other materials  of different colors. Mosaicism may also result from the abnormal behaviors of chromosomes during the cell division in the fetus. A female is a mosaic because she consists of a mixture of two kinds of cells: each with different functional chromosomes. Because XY males have a single X chromosome, while XX females have two of them, some kind of adjustment is needed: the X chromosome inactivation. Because of this X inactivation, all women are natural mosaics: although all their cells have the same two chromosomes, one from each parent, the mother’s copy works in some cells, while the father’s works in the others. The two kinds of cells often function differently, especially if one of chromosomes carries a defective gene: for this reason, Barbara Migeon underlines that women are superior to men in coping with disease and the environment. They have two types of cells in all their organs, each with one of the two X chromosomes genetically active and the other essentially silent. This allows adaptability, since each of the two X chromosomes carries different mutations and polymorphisms that can alter women's susceptibility or resistance to detrimental genes, infectious agents, or other environmental dangers.

Much has been written about the Y chromosome and its role in inducing maleness. Little has been said about the blue prints for female development, or about the role of biological factors, other than hormones, as the cause of sex differences in human disease.^. The X chromosome is extraordinary, because it is the only chromosome subject to programmed inactivation.

Many biologists who work in this field do not realize the clinical implications because they work with inbred animals whose maternal and paternal X chromosomes are genetically identical.

Much of the book is devoted to the reason for this state of mosaicism, which allows males and females to express equal quantities of proteins that are coded by genes on the X chromosome. Otherwise, females could have more of these proteins, a situation which in some settings could be incompatible with life. The formal term for the silencing of the two X chromosomes in the female is X inactivation, a phenomenon that was initially discovered in mice by Mary Lyon in 1961. This led Lyon to postulate that one X chromosome in each cell was inactivated and that the process was random. She also showed that once an X was inactivated, the same X remained permanently inactive in all the cells that were derived from the cell in which inactivation occurred.

Following the approach of mosacism, the author introduces the subject of differences in diseases, and the evidence that males are biologically more vulnerable than are females at most stages of their lives. Vulnerability of males leads to sex-specific disease. It provides the evidence that many sex-specific diseases have their basis in X chromosome biology.

Further the author is focusing on the evolution of sex chromosomes, which has led to degeneration of the Y chromosome.

Then the attention is focused on the X chromosome degeneration, and next on the X inactivation, or rather X dosage compensation. Sex dosage compensation is intimately related to sex determination in every organism in which occurs. One of the two sexes must undergo dosage compensation, or it cannot become a female or a male.

Epigenetic factors are responsible for the silent X. Inactivation occurs early in the embryonic development, and it is not possible directly to observe it. Although the fundamental mechanism of X inactivation is thoroughly discussed and analyzed in the book, a number of questions remain to be resolved. For example, the mechanism by which all but one X chromosome are selected for inactivation is not totally clear. Gene activity relates to the mechanism of X inactivation by way of a control region (inactivation center) on the X chromosome that contains a gene (X-inactivation–specific transcript, or XIST) that produces an RNA that causes inactivation along the length of the chromosome. The methylation of CpG (cytidine–phosphate–guanidine) islands, turns off gene activity in all chromosomes. It is not entirely clear how the inactivating gene, XIST, causes this change in the X chromosome, but the result is the same as in the temporary or permanent inactivation of genes that are not needed in the cells of particular tissues. This process of methylation is also related to the mechanism of imprinting, in which the silencing of some genes depends on which parent they come from. Such imprinted genes exist throughout the human genome. Epigenetic changes have important role in the pathogenesis of many rare diseases, including premature aging, and in the common ones such as cancer and mental retardation.

The mechanisms that stabilize X inactivation after it occurs, is transferred as a memory of which X has been selected to the cell’s progeny. The biological and clinical advantages of mosaicism are discussed in relation to genetic diseases and the enhanced variability afforded to mosaic females. The clinical importance of the single active X chromosome in both genders is discussed: the other chromosomes (autosomes) occur in pairs and provide two sets of genes, both copies working in each cell; having a single active means that any cell, whether female and male, has only one set of functional X-linked chromosome.  

The third and last part are interesting the clinician: they consist of three chapters related to the medical consequences of X inactivation. The first of these chapters explains sex differences in susceptibility to X chromosome aneuploidy, such as in Turner's syndrome, Klinefelter's syndrome, and the triple X syndrome, as well as in deletions of different parts of the X chromosome and translocations of parts of the X chromosome to autosomes. This last problem is particularly important in that the X, that is translocated to an autosome, is always the active one, since the inactivation mechanism would also inactivate the autosome to which it is attached. This means that the same X is active in all cells of a woman who is carrying a translocation and that, therefore, any mutation in that X will express itself as if the woman were a man.

The next chapter in this section relates to the effect of mosaicism, which is particularly relevant in the carriers of some types of mutations of genes on the X chromosome. The specific mutation that a person carries may cause selection against the cells in which the X that carries the mutation is active, thus preventing any manifestation of the disease (e.g., X-linked severe combined immunodeficiency). In other situations, the mutation may give an advantage to the cell in which it is active and cause the disease to manifest itself in the carrier (e.g., adrenoleukodystrophy).  The patch size differs from tissue to another. For many metabolic functions it may not be necessary that all cells within the relevant tissues are functional. The protein lacking in mutant cells can be furnished by the normal cells.

The last chapter is about the effects of the interacting cell populations on the health of women and the effects of X inactivation on the normal female phenotype. X inactivation is determinant of clinical phenotype.

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