Figure 254

Electron micrographs of nuclei from two different cell types.

The large electron micrograph shows the nucleus of a nerve cell. Two nucleoli are included in the plane of section. The nucleus of this active cell, exclusive of the nucleoli, is comprised almost entirely of extended chromatin or euchromatin. xl0,000. Inset. The smaller nucleus belongs to a circulating lymphocyte (the entire cell is shown in the micrograph). It is a relatively inactive cell. Note the paucity of cytoplasm and cytoplasmic organelles. The chromatin in the nucleus is largely condensed (heterochromatin). The lighter areas represent euchromatin. X13,000.

The smallest units of chromatin structure are macromolecular complexes of DNA and histones, called nucleosomes

Nucleosomes are found in both euchromatin and heterochromatin and in chromosomes (see below). A nucleo-some is a 10-nm-diameter particle that consists of a core of eight histone molecules. Approximately two loops of DNA

(about 146 nucleotide pairs) are wrapped around the core octamer. The DNA extends between each particle as a 1.5-nm filament that joins adjacent nucleosomes. The nu-cleosomal substructure of chromatin is often described as "beads on a string"

A long strand of nucleosomes is coiled to produce a unit chromatin fibril that is about 25 to 30 nm in diameter. Six nucleosomes form one turn in the coil of the chromatin fibril. Both interphase chromatin and chromosomes are formed from the 25- to 30-nm unit fibril. In heterochro-matin, the unit chromatin fibrils are tightly packed and folded on each other; in euchromatin, the unit fibrils are more loosely arranged. This loose arrangement allows DNA polymerases access to the DNA in euchromatin.

In dividing cells, chromatin is condensed and organized into discrete bodies called chromosomes

Chromosomes [Cr„ colored bodies] are formed during mitosis by condensation of the euchromatin and combination with heterochromatin. Each chromosome is formed by two chromatids that are joined together at a point called the centromere. The double nature of the chromosome is produced in the preceding synthetic (S) phase of the cell cycle (see page 69), during which DNA is replicated in anticipation of the next mitotic division.

The area located at each end of the chromosome is called the telomere. Telomeres shorten with each cell division. Recent studies indicate that telomere length is an important indicator of the lifespan of the cell. To survive indefinitely (become "immortalized"), cells must activate a mechanism that maintains telomere length. For example, in cells that have been transformed into malignant cells, an enzyme called telomerase is present that adds repeated nucleotide sequences to the telomere ends. Recently, expression of this enzyme has been shown to extend the life span of cells.

With the exception of the mature gametes, the egg and sperm, human cells contain 46 chromosomes organized as 23 homologous pairs (each chromosome in the pair has the same shape and size). Twenty-two pairs have identical chromosomes, i.e., each chromosome of the pair contains the same portion of the genome, and are called autosomes. The twenty-third pair of chromosomes are the sex chromosomes, designated X and Y. Females contain two X chromosomes; males contain one X and one Y chromosome. The chromosomal number, 46, is found in most of the somatic cells of the body and is called the diploid (2n) number. Diploid chromosomes have the 2n amount of DNA immediately after cell division but have twice that amount, i.e., the 4n amount of DNA, after the S phase (see page 69).

As a result of meiosis (see below), eggs and sperm have only 23 chromosomes, the haploid {In) number, as well as the haploid {In) amount of DNA. The somatic chromosome number and the diploid (2n) amount of DNA are reestablished at fertilization by the fusion of the sperm nucleus with the egg nucleus.

In a karyotype, chromosome pairs are sorted according to their size and shape

A preparation of chromosomes derived from mechanically ruptured, dividing cells that are then fixed, plated on a microscope slide, and stained with Giemsa stain is called a metaphase spread (Fig. 2.55a). Such spreads are then photographed. The chromosome pairs are cut from the photograph and sorted according to their morphology to form a karyotype (Fig. 2.55b). Karyotypes are used to detect chromosome abnormalities such as deletions, nondisjunctions, and additions; for determination of sex in fetuses; and for prenatal diagnosis of certain genetic disorders. Special stains and molecular probes allow study of localized regions of specific chromosomes to determine duplications or deletions of specific gene sites (loci).

The Barr body can be used to identify the sex of a fetus

Some chromosomes are repressed in the interphase nucleus and exist only in the tightly packed heterochromatic form. One X chromosome of the female is an example of such a chromosome. This fact can be used to identify the sex of a fetus. This chromosome was discovered in 1949 by Barr and Bartram in nerve cells of female cats, where it appears as a well-stained round body, now called the Barr body, adjacent to the nucleolus.

Although the Barr body was originally found in sectioned tissue, it was subsequently shown that any relatively large number of cells prepared as a smear (e.g., scrapings of the oral mucous membrane from the inside of the cheeks or neutrophils from a blood smear) can be used to search for the Barr body. In cells of the oral mucous membrane, the Barr body is located adjacent to the nuclear envelope. In neutrophils, the Barr body forms a drumstick appendage on one of the nuclear lobes (Fig. 2.56). In both sections and smears, many cells must be examined to find those whose orientation is suitable for the display of the Barr body.

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