It is the study of the human genome. It includes identifying genes, determining their function, mode of transmission, and inheritance. It also detects mutated genes or genes that do not work.
It develops to know who humans are and why they are the way they are. On a more practical level, an understanding of human inheritance is of critical importance in the prediction, diagnosis, and treatment of diseases that have a genetic component.
The human chromosomes
Genetic research has advanced with surprising speed and has shown that human chromosomal aberrations are the leading causes of fetal death or are accompanied by mental retardation.
Since chromosomes can be delineated only during mitosis, it is necessary to examine the material in which there are many dividing cells.
This can usually be achieved by culturing blood or skin cells since only cells in the bone marrow (which are not easily sampled except during severe diseases such as leukemia) have sufficient mitosis in the absence of artificial culture.
After growth, the cells are fixed on slides and then stained with various specific DNA stains that allow the delineation and identification of the chromosomes.
Micrographs showing the karyotypes (i.e., the physical appearance of the chromosome) of a male and a female have been produced.
In a typical micrograph, the 46 human chromosomes (the diploid number) are arranged in homologous pairs, each composed of a member derived from the mother and one derived from the father.
All the chromosomes are numbered, except the X and Y chromosomes, which are the sex chromosomes. As in all mammals, the average female has two X chromosomes, and the typical male has an X chromosome and a Y chromosome.
The female is thus the homogametic sex since all its gametes typically have an X chromosome.
The male is heterogametic since it produces two types of gametes: one type that contains an X chromosome and the other that has a Y chromosome. There is good evidence that the Y chromosome in humans, unlike Drosophila, is necessary for masculinity.
Fertilization, sexual determination, and differentiation
A human individual arises through the union of two cells, the mother’s ovum and the sperm of the father. The human ovules are barely visible to the naked eye.
They are removed, usually one at a time, from the ovary to the oviducts (fallopian tubes), through which they pass into the uterus. Fertilization, the penetration of an egg by a sperm, occurs in the oviducts.
This is the main event of sexual reproduction and determines the genetic constitution of the new individual.
The determination of the human sex is a genetic process that depends on the presence of the Y chromosome in the fertilized egg. This chromosome stimulates a change in the undifferentiated gonad in the male (a testicle).
The gonadal action of the Y chromosome is mediated by a gene located near the centromere; this gene encodes the production of a cell surface molecule called HY antigen.
The further development of anatomical structures, both internal and external, that are associated with masculinity is controlled by the hormones produced by the testicle.
The sex of an individual can be thought of in three different contexts: chromosomal sex, gonadal sex, and anatomical sex. The discrepancies between these, especially the last two, result in the development of individuals with ambiguous sex, often called hermaphrodites.
The phenomenon of homosexuality is of uncertain cause and is not related to the determinants above of sex. It is interesting that, in the absence of a male gonad, the internal and external sexual anatomy is always female, even in a female ovary.
A woman without ovaries, of course, will be infertile and will not experience any of the changes in female development customarily associated with puberty. Such a woman will often have Turner syndrome.
If the sperm containing X and Y are produced in equal numbers, then, according to the simple possibility, one would expect the sex ratio at conception (fertilization) to be half of the boys and half of the girls, or eleven.
During pregnancy, the nine months between fertilization and the baby’s birth, there is a remarkable series of changes in development. Through mitosis, the total number of cells changes from 1 (the fertilized egg) to approximately 2 × 1011.
In addition, these cells are differentiated into hundreds of different types with specific functions (liver cells, nerve cells, muscle cells, among others).
A multitude of regulatory processes, both genetically and environmentally controlled, achieve this differentiation. The elucidation of the exquisite time of these processes remains one of the significant challenges of human biology.
Immunity is the ability of an individual to recognize the molecules that make up the organism and distinguish them from “non-self” molecules such as those found in infectious microorganisms and toxins. This process has a prominent genetic component.
There are two primary components of the immune system, both originating from the same “mother” precursor cells.
The bursa component provides B lymphocytes, a class of white blood cells that, when properly stimulated, differentiate into plasma cells. These last cells produce circulating soluble proteins called antibodies or immunoglobulins.
An antibody molecule can recognize a specific antigen, combine it, and initiate its destruction. This so-called humoral immunity is achieved through a complicated series of interactions with other molecules and cells.
Some of these interactions are mediated by another group of lymphocytes, T lymphocytes, derived from the thymus gland.
Once a B lymphocyte has been exposed to a specific antigen, it “remembers” the contact so that future exposure causes an accelerated and magnified immune reaction. This is a manifestation of what has been called immunological memory.
The thymus component of the immune system focuses on the T-derived thymus lymphocytes. In addition to regulating B cells to produce humoral immunity, T cells also directly attack cells that show foreign antigens.
This process, called cellular immunity, is of great importance in protecting the body against various viruses and cancer cells. Cellular immunity is also the leading cause of the rejection of organ transplants.
T-lymphocytes provide a complex network consisting of a series of helper cells (which are antigen-specific), amplifying cells, suppressor cells, and cytotoxic (killer) cells, all of which are important in immune regulation.
The genetics of antibody formation
One of the central problems in understanding the genetics of the immune system has been to explain the genetic regulation of the production of antibodies.
Immunobiologists have shown that the system can produce more than one million specific antibodies corresponding to a particular antigen.
It would be difficult to imagine that each antibody is encoded by a separate gene; such an arrangement would require disproportionate participation of the entire human genome.
Recombinant DNA analysis has illuminated how a limited number of immunoglobulin genes can encode this large number of antibodies.
The genetics of cellular immunity
The control of cellular immune reactions is provided by a linked group of genes known as the major histocompatibility complex (MHC).
These genes encode the major histocompatibility antigens, which are found on the surface of almost all nucleated somatic cells.
The major histocompatibility antigens were first discovered in leukocytes (white blood cells) and, therefore, are known as HLA antigens (group of human leukocytes A).
The genetics of human blood
More is known about the genetics of blood than about any other human tissue. One reason is that blood samples can be easily secured and subjected to a biochemical analysis without causing significant damage or discomfort to the person being evaluated.
Perhaps a more compelling reason is that many chemical properties of human blood show relatively simple inheritance patterns.
Geneticists have identified approximately 14 blood type gene systems associated with other chromosomal locations.
The best known of these is the Rh system. Rh antigens are of particular importance in human medicine.
For some people (Rh-negative individuals), the Rh gene evidence indicates that only a single chromosomal locus (called r) is involved and located on chromosome 1. At least 35 Rh alleles are known for the r location; Basically, the adverse Rh condition is recessive.
A medical problem can arise when a woman who is Rh-negative carries a fetus that is Rh-positive.
The first child of this type may not have difficulties, but later similar pregnancies may produce newborn babies with severe anemia.
Exposure to the red blood cells of the first Rh-positive fetus appears to immunize the Rh-negative mother, that is, develops antibodies that can cause permanent (sometimes fatal) brain damage in any subsequent Rh positive fetus.
The damage arises from the shortage of oxygen that reaches the fetus’s brain due to the severe destruction of red blood cells.
There are measures to avoid the severe effects of Rh incompatibility by transfusions to the fetus inside the uterus.
However, genetic counseling before conception is helpful so that the mother can receive Rh immunoglobulin immediately after her first pregnancy and any subsequent pregnancy involving an Rh positive fetus.
This immunoglobulin effectively destroys fetal red blood cells before the mother’s immune system is stimulated. Therefore, the mother avoids being actively immunized against the Rh antigen and will not produce antibodies that could attack the red blood cells of a future Rh positive fetus.
A fertile human female generally produces a single egg approximately once a month. If fertilization occurs (a zygote forms), the growth of the individual child usually occurs after the fertilized egg has been implanted in the wall of the uterus.
In the unusual circumstance that two unfertilized ovules are released simultaneously by the ovaries, each ovule can be fertilized by a different sperm simultaneously, implanted and grow to result in the birth of twins.
Twins formed from separate eggs and different sperm cells can be the same or of either sex.
No matter what their sex, they are designated as fraternal twins. This terminology emphasizes that fraternal twins are genetically no more similar than their brothers (or sisters) born years apart.
They differ from the ordinary brothers only in having grown side by side in the womb and being born at about the same time.
In a type of non-main twinning, only one egg is fertilized, but during the division of this single zygote into two cells, the resulting pair is separated somehow.
Each of the two cells can be implanted in the uterus separately and become a complete individual.