Cells In Genetics

In point mutation through microscopy or microbiology there is a loss or change of function of a gene, caused by a defect in the DNA that may lead to formation of an abnormal enzyme or other type of protein or be responsible for lack of production of certain enzymes. Examples of diseases as studied in pathology and microbiology, and examined under the microscopes, characterized by such biochemical genetic disturbances are the hemoglobinopathies such as sickle cell disease, in which abnormal hemoglobins are produced by mutations in the genes controlling the formation of the globin portion of the hemoglobin molecule, and inborn errors of metabolism, in which deficiency of a specific enzyme is evident such as aIcaptonuria, phenylketonuria, glycogen storage diseases, galactosemia, cystinuria, homocystinuria, Wilsons hepatolenticular degeneration, and many others.

Chromosomal Aberrations

Through microscopy and with the aid of microscope photo, chromosomal aberrations characterized by alterations in number or structure of chromosomes are known to occur in association with a variety of disorders. Before referring to some of the abnormalities, however, it should be recalled that normally under the microscopes each sex cell, or gamete, contributes 23 chromosomes to the fertilized ovum, 22 autosomes and a Y or X chromosome. As discovered using the microscopes, the sperm contributes either a Y or an X chromosome and the ovum only an X chromosome. Each cell of a normal person, except for the gametes, contains 46 chromosomes, 22 pairs of homologous autosomes and a pair of sex chromosomes, XX in females and XY in males as studied by means of the microscopes.

In microscopy, chromosomal aberrations affect both autosomal and sex chromosomes. The frequency of chromosomal abnormalities among unselected infants born alive is about 0.5 percent. In a recent survey, chromosomal abnormalities were noted in 5.6 percent of unselected infants dying in the perinatal period. The frequency was 13 percent among infants with malformations both stillbirths and neonatal and 2.5 percent among infants dying from other causes. In studies of spontaneous abortions during the early phases of pregnancy, chromosomal abnormalities are found usually in about 35 percent of the fetuses as examined through the microscopes. In the surviving patients with alterations of chromosomes, structural anomalies and abnormal function of many organs are frequently associated as observed with the help of the microscopes. Mental retardation commonly occurs in clinical disorders associated with chromosome abnormalities especially in those with autosomal anomalies. In general, autosomal defects are associated with more severe physical and mental disturbances than sex chromosome abnormalities as examined under the various microscopes such as light microscope or electron microscope.

Chromosome Analysis

In microbiology and microscopy chromosomes are usually studied in cells that are grown in tissue cultures, either leukocytes obtained from the blood or cells derived from a small specimen of living tissue. Even amniotic fluid cells obtained from pregnant women by amniocentesis have been studied successfully for detection of genetic disorders in the fetus through microscopy. Under the microscopes, the dividing cells are treated with colchicine, which halts them at the metaphase then a hypotonic salt solution is added to cause swelling of the nuclei and separation of the chromatids, with the centromeres left intact. After the cells are fixed, placed on slides, stained, and examined through microscopy, a photograph is made and enlarged such process is known as microscope photo or micrography. Each chromosome is cut out of the picture, arranged in pairs, and classified into seven groups on the basis of size of chromosomes and position of the centromere, and each pair of autosomal chromosomes is numbered in the order of decreasing size. The X chromosome resembling those oil the C6C12 group, especially chromosome 6 and the Y chromosome are not numbered. This systematic arrangement of the photographs, taken through the use of the microscope, of the chromosomes is referred to as the karyotype. The word idiogram is sometimes used synonymously, but strictly used this term applies to a diagrammatic representation of a karyotype.

A standardized system for describing the karyotype was proposed at a conference in Chicago in 1966 and modified at another conference in Paris in 1971. By means of symbols, the total number of chromosomes, the sex chromosome complement, and the description of the anomaly are noted. A plus or minus sign placed before a chromosome letter or number indicates additional or missing whole chromosomes. A plus or minus sign placed after a symbol designating the short or long arm, the letter p representing the short arm and q, the long arm. Translocation is indicated by the letter t followed by parentheses, which include the chromosomes involved. The letter i placed after the chromosome arm involved indicates an isochromosome. An r placed after a chromosome indicates a ring chromosome. Other symbols are used to express the remaining types of chromosomal anomalies.

In preparing karyotypes by the conventional means, it is sometimes difficult to distinguish between chromosome pairs in the various groups. The use of autoradiography has permitted distinctions in some but not all groups. New chromosome staining techniques, such as quinacrine fluorescent and Giemsa methods, demonstrate structural details such as banded regions on chromosomes that are characteristic for each chromosome as observed under the microscopes. These methods through microscopy not only permit easier identification of chromosomes, but also increase the information that may be obtained by study of individual chromosomes.

By means of a different technique, using a special computer, the time needed to process the chromosomes has been reduced considerably. The computer is programmed to count the number of chromosomes, measure their length, and recognize other morphologic features in an unenlarged photograph of chromosomes that have not been rearranged. Sandberg and associates have used successfully a direct fixation method of studying freshly aspirated bone marrow that does not require culturing of cells or treatment with colchicine.

Alterations in Number

As observed under the microscopes, an abnormal number of chromosomes may result from nondisjunction in meiosis, which is a failure of the usual separation of two chromosomes of a pair, so that one daughter cell receives both and the other daughter cell receives neither chromosome of the pair. A gamete with an extra chromosome, which is 24 chromosomes fertilizing a normal gamete, which is 23 chromosomes results in a trisomic zygote, as seen under the microscopes. Such an abnormality is seen in mongolism or Downs syndrome, in which there is a trisomy of one of the autosomal chromosomes, number 21, with the result that there are total of 47 chromosomes in that individual. Trisomies may involve other autosomal chromosomes. They may also be noted in certain abnormalities of the sex chromosomes, as in Klinefelters syndrome, in the triple X syndrome, and in males with an extra Y. When only one chromosome is present instead of the usual pair, the abnormality is referred to as a monosom. For example, in the monosomic state known as Turners syndrome, only one sex chromosome, an X, exists. Monosomes with only a Y chromosome are not known to occur. In some sex chromosomal aberrations, the individual may have more than one extra chromosome, as in variants of Klinefelters syndrome and in some multi X females as examined in microscopy or microbiology. Another type of chromosomal abnormality that may occur is mosaicism, the presence of cells in the same individual that differ in their chromosomal constitution. This defect apparently arises during mitosis after fertilization, perhaps as a result of nondisjunction or complete loss of a chromosome in the early stages of growth of the zygote as observed using the microscopes.