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Medical Specializations


Immunology => Cell => Chromosomes


Chromosomes


INTRODUCTION
Chromosome, microscopic unit within cells that contains deoxyribonucleic acid (DNA)-the hereditary material that influences the development and characteristics of each organism. In bacteria and bacteria-like organisms called archaebacteria, chromosomes consist of simple circles of DNA free-floating in the organism. In all other life forms, collectively called eukaryotes,chromosomes are highly complex structures in which the DNA molecules have a linear, rather than a circular, shape. In these organisms, chromosomes are found within a well-defined nucleus and they are composed of chromatin, which contains proteins as well as DNA.

CHROMOSOME STRUCTURE
The chromosomes of eukaryotes function as packaging units, maintaining an organized structure for the DNA within a microscopically small space, while also enabling DNA to carry out its key functions. For example, each human cell contains enough DNA to form a thread extending about 1.5 m (about 5 ft), yet this DNA fits inside the cell nucleus, a cellular compartment that is only a few micrometers in diameter (about one-millionth of an inch). Chromosomes ensure that even when the DNA is highly confined it is free to carry out transcription-the process of guiding the production of messenger ribonucleic acid (mRNA), the molecule that determines the types of proteins a cell will produce. In addition, chromosomes permit DNA to replicate, or reproduce itself, so that as a cell divides to produce two cells, each of these will contain all of the necessary genetic information.

Proteins called histones play a key role in packaging DNA within chromosomes. Because histones have a positive electrical charge, they readily attach to DNA, which has a negative charge. Sections of the DNA molecule wind around clusters of histones to form units called nucleosomes, which resemble spools encircled with thread. Nucleosomes are separated from one another by strands of unwound DNA, called linker DNA. When viewed through an electron microscope, strands of linker DNA interspersed with nucleosomes look like strings of beads. Strands of linker DNA and nucleosomes, called chromatin fibers, undergo several additional levels of packaging, aided by histone proteins, which create a structure in which the nucleosomes are brought close together and stacked into a narrow coil. Another type of protein, called nonhistone chromosomal proteins, helps to make the chromatin even more compact. Chromosomes become most condensed when a cell is preparing to divide.

Scientists are learning how DNA loosens its connection with histones in order to replicate itself and participate in the synthesis of mRNA. Evidence suggests that specialized proteins called enzymes interact with the tails of histones, which protrude from the nucleosomes. These interactions may temporarily disrupt the nucleosome structure, so that the DNA is free to interact with the enzymes that help to generate either mRNA or new copies of DNA.

CENTROMERES AND TELOMERES
Two important structures, called centromeres and telomeres, are found in the chromosomes of nearly all eukaryotic life forms. During cell division, the centromere-visible through a microscope as a knot-like structure-connects to an apparatus called the spindle. The spindle contains fibers that move the centromeres around, causing the rest of each chromosome to follow. This process ensures that each chromosome moves to its proper place during mitosis, when a cell divides to give rise to two cells, and during meiosis, the process of cell division that gives rise to eggs or sperm.
Telomeres are specialized sequences of DNA that are found at the tips of chromosomes. Telomeres serve as a kind of cap that prevents the ends of chromosomes from attaching to the ends of other chromosomes. Scientists suspect that telomeres may influence the activity of nearby genes and may also play a role in determining the life span of a cell.

CHROMOSOME NUMBER
In the cells of most organisms that reproduce sexually, chromosomes occur in pairs: one that is inherited from the female parent, and one that is inherited from the male parent. The two chromosomes of each pair contain genetic information that corresponds to the same inherited characteristics. Each pair of chromosomes is different from every other pair of chromosomes in the same cell.

The number of chromosome pairs varies considerably depending on the species. The number of chromosomes in an organism's somatic cells-all cells except for those that give rise to sex cells, such as eggs or sperm-is called the diploid number. Dogs, for example, have 38 pairs of chromosomes and a diploid number of 76, while tomato plants have 12 pairs of chromosomes and a diploid number of 24.

Female sex cells, or eggs, and male sex cells, or sperm, contain only half the number of chromosomes found in the somatic cells-one chromosome from each pair. This reduced number of chromosomes in the sex cells is known as the haploid number. During fertilization, an egg and sperm unite to form a cell known as a zygote, the first cell of the offspring. The zygote contains the diploid number of chromosomes characteristic of the species.

HUMAN CHROMOSOMES
Humans have 23 pairs of chromosomes, with a diploid number of 46. Twenty-two of these pairs are called autosomes; these chromosomes serve the same functions in both male and females. The remaining pair of human chromosomes is called the sex chromosomes, because this pair plays a dominant role in determining the sex of the individual. Females have two copies of the female-determining, or X chromosome, while males have one male-determining, or Y chromosome, and one X chromosome. Both males and females inherit one sex chromosome from the mother (always an X chromosome) and one sex chromosome from the father (an X in female offspring and a Y in male offspring).

In the reproductive cells of humans, like those of other organisms, errors may occur that give rise to embryos with more or less genetic material than is typical for the species. One source of such errors is a process called nondisjunction, in which paired members of chromosomes fail to separate from one another during meiosis. Nondisjunction can lead to a condition known as Down syndrome, in which a person has three copies of a small chromosome designated as chromosome 21. Another condition that may result from nondisjunction is known as Turner's syndrome in which the individual, a female, has a single X chromosome and no Y chromosome. Genetic errors may also occur when part of a chromosome is either deleted or duplicated. Chromosomes sometimes undergo changes called translocations, in which part of one chromosome breaks off and attaches to another chromosome. A translocation involving chromosomes 9 and 22 is linked to a type of leukemia called chronic myelogenic leukemia.

Scientists called cytogeneticists look at a person's chromosomes in the laboratory to determine whether the individual has the usual number of chromosomes and whether these chromosomes have missing or extra segments. To examine chromosomes, cytogeneticists grow samples of a person's blood cells in the laboratory and expose the cells to a chemical called colchicine, which disrupts the spindle apparatus that is normally present in dividing cells. This disruption immobilizes the chromosomes during cell division, the time when the chromatin is in its most condensed state. Chromosomes are then stained with various dyes to induce a pattern of vertical bands. Cytogeneticists take photographs of the banded chromosomes through a microscope and create graphic images called karyotypes, in which the members of each chromosome pair are arranged next to each other for easy comparison. The analysis of karyotypes reveals whether a person has extra or missing chromosomes, as well as whether large segments of chromosomes are absent, rearranged, or duplicated.

Experiments involving artificial chromosomes-chromosomes that are synthesized in the laboratory-are providing new insights into the structure and function of chromosomes. The first artificial chromosomes, produced in the 1980s, were chromosomes of yeast cells. The first artificial human chromosomes were created in 1997.

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