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Human genetics HUMAN SEX CHROMATIN Sex chromosomes In humans, the sex chromosomes are labeled X and Y. Females have two X chromosomes and males have one X and one Y chromosome. All the eggs produced during meiosis have an X chromosome. Half of the sperm produced by a male contain an X chromosome and the other half have a Y chromosome. Thus, sperm determine the sex of the offspring. If the egg is fertilized by a sperm with an X chromosome, the zygote develops into a female. If the sperm contains a Y chromosome, the offspring is a male. There is a difference between the sex chromosomes. While the X chromosome is relatively large (approximately 6% of nuclear DNA), the Y chromosome is quite small, and only a few genes have been assigned to it. X-chromosome inactivation In 1961, the British geneticist Mary Lyon proposed that the X chromosomes in somatic cells of mature females are of two types. One is active and expresses its full complement of genetic information; the other is inactivated in some manner and does not serve as a source of genetic information. The biological meaning of suppression of the functional activity of one of two X chromosomes is the dose compensation, as in male karyotypes there is only one X chromosome present, and in female two. Thus the genotypic possibilities of male and female karyotype are equalized. It is important that this inactivation occurs randomly, so that in early embryonic life (after 16 days) different cell may have alternative X chromosomes inactivated. So in some cells the X-linked genes inherited from the mother are expressed, whereas in other cells, the X-linked genes inherited from the father are active. Thus, the somatic tissues of females are said to be mosaic because they represent the contribution of genes from different X chromosomes. In which somatic cell will express the genes in only one X chromosome, but the X chromosome that is genetically active will differ from cell to cell. This mosaicism has been observed directly in women who are heterozygous for an X-linked recessive mutation resulting in the absence of sweat glands; these women exhibit patches of skin in which sweat glands are present (these patches are derived from embryonic cells in which the normal X chromosome remained active and the mutant was inactivated), and other patches of skin in which sweat glands are absent (these patches are derived from embryonic cells in which the normal X chromosome was inactivated and the mutant X remained active). HUMAN SEX CHROMATIN The molecular basis for X chromosome inactivation is not completely understood. The process begins with activation of a gene called X-inactivation-specific transcript (XIST) on the long arm of the X chromosome. XIST is expressed only in the inactive X chromosome and produces an RNA molecule (not translated into protein) that transmits the inactivation signal throughout the chromosome. The process involves physical reorganization of the DNA within the chromatin and also the addition of methyl groups to the DNA bases of substantial regions of the inactivated X chromosome. Sex chromatin (Barr Bodies) Sex chromatin (or Barr bodies) is normally one X chromosome, which in interphase nucleus is completely or partially coiled. One of the two X chromosomes in female cells is facultatively heterochromatic and is condensed during interphase forming the Barr body. A Barr body is about 1 micrometer in diameter and is located at the periphery of the nuclear membrane. The number of Barr bodies is one less than the number of X chromosomes. Although cells of normal females have one Barr body, cells of normal males have none. Individuals with two or more X chromosome have a number of Barr bodies equal to the number of X chromosomes minus one (that is, equal to the number of inactivated X chromosomes). For example, XXX individuals have two Barr bodies, XXXX individuals have three, and XXXXX individuals have four. Thus, an XYY male has no Barr bodies, and XXY or XXYY males have one Barr body. Determination of X-chromatin in mucosa cells Barr bodies can be determined most easily in bucal mucosa, hair roots and fibroblast cells. The normal positive range for sex chromatin bodies is 20-60 percent. Determination of sex chromatin in mucosa cells includes the following stages: 1) making the preparation; 2) microscope analysis of the preparation; 3) making of conclusions. Epithelium cells of the mucosa on the inside of cheek serves as a material. Before taking the scrape of the cells, the mouse should be rinsed with clean water. Using a sterile scalpel a scrape is made on the inside of the cheek. The scrape is spread over the object-plate, which is dipped into methyl alcohol for fixation. 10-15 minutes later the preparation is taken out of the alcohol, air-dried. Then one or two drops of acetoorceine are dropped on the preparation, the preparation is covered with a cover-glass and the excess of dye is removed by blot. Microscopical examination of preparation. When the preparation is studied by microscope only those nuclei are taken into account, in which the chromatin appears as oval or kidney-shaped bodies, They are usually localized by the inner 2 HUMAN SEX CHROMATIN surface of nuclear envelope. About 100-150 cells are analyzed, those containing Barr bodies are counted. The frequency of cells containing Barr bodies is calculated in %. Examination of Barr bodies is a rapid and convenient test. It is useful to: determine the sex in prenatal stage; determine the sex of a person with ambiguous genitalia , detect abnormal karyotypes such as Turners syndrome and Klinefelter syndrome. Y-chromatin Y-chromatin or F body is formed by 2/3 of q arm of the Y chromosome and can be observed microscopically as a intensive fluorescent staining body in the nucleus of interphase cells. Its size is about 0,25 microns and it is situated apart (separately) or being attached to nuclear membrane. The frequency of cells containing F bodies varies in different tissues of male organism. For example, it is 70-85% in fibroblatst and it is about 45% in sperm cells. The number of Y-chromatin bodies is equal with the number of Y-chromosomes. Thus, cells of normal females have no F bodies, cells of normal males have one F body, XYY males have two F bodies. 3