Basics of genetic diseases – autosomal dominant, autosomal recessive

Proven content

A genetic condition can be described as a deviation from normal health that results from altering the genetic information stored in DNA. The disease may show up in the family for the first time or be passed down from generation to generation.

In order to understand the essence and occurrence of genetically determined diseases, at least basic knowledge about the structure and function of DNA is needed. Deoxyribonucleic acid – DNA – carries information about the structure of all proteins that make up the human body, stored in its structure. It is located in the cell nucleus of the vast majority of cells that make up the human body. Small DNA component fragments form single strands in a linear arrangement. Two appropriately selected and corresponding DNA strands form a helically twisted structure called a helix. This is how DNA is usually depicted in illustrations or models. A gene, on the other hand, is a linear set of sequences on DNA strands, in which information is written about how proteins are composed of, among others, our skin, internal organs, fluids and enzymes.

The DNA double helix goes through the packing processes and the final form is the chromosome. It is in the form of chromosomes that DNA is found in the nucleus of cells. Each species of plants and animals has a characteristic chromosome arrangement – we call it the karyotype. A normal cell in the human body contains 23 pairs of chromosomes. One chromosome in each pair is from the mother, the other from the father. The last pair are sex chromosomes – XX for women and XY for men.

Any change that occurs in a gene can be reflected in a change in the structure of the protein that was encoded by that gene. Sometimes it has no clinical significance and does not cause disease, but there are cases of minor changes causing severe dysfunction. Such changes are called mutations.

Monogenic mutations – individual genes in chromosomes can arise as new “phenomena” or be inherited from parents or grandparents. This inheritance follows the rules of inheritance defined by Gregor Mendel, a religious and precursor of genetics. He conducted research on the inheritance of pea traits and proved that inheritance of pea traits is based on a set of laws. Two mechanisms are most important: domination and recessivity. Dominance means that only one copy of the mutated gene – from one of the parents – is enough to reveal clinical symptoms of a gene mutation. For the recessive trait to manifest itself, two copies of the “broken” genes are needed – one from each parent. There is autosomal inheritance. If the transferred mutation is on the chromosome associated with the sex, it is referred to as sex-linked inheritance.

Autosomal dominant

Criteria for this type of inheritance:

– a given feature is passed down from one generation to the next

– a sick child has a sick parent (unless it is a newly created mutation – it is so severe that it reduces the possibility of reproduction)

– if the mutation is not found in the sex chromosome, then individuals of both sexes suffer the disease equally frequently

In autosomal dominant inherited diseases, the so-called variability of expression. It consists in the differentiation of the clinical form of the disease and the different intensity of its features. In the case of genetic counseling in such families, it is important to take a careful history and check family members for mild symptoms.

Autosomal recessive

Criteria for this type of inheritance

– parents and relatives of a sick child are usually healthy (if the feature is rare)

– the incidence of the disease is the same in both sexes

– if the trait is rare, it is likely that the parents are related

Due to the fact that two damaged copies of the gene are required for the occurrence of the disease, the phenomenon of carrier occurs in this case. A carrier is a person who has only one copy of the defective gene. May have no or only slight clinical symptoms. If his partner becomes a person who has a similar mutation, they are 25% likely to have a sick child, 25% of their child will be healthy and not a carrier, and 50% will be a carrier of the mutated gene.

Another disorder in the transmission of genetic material to offspring are chromosomal aberrations. They concern such large chromosome abnormalities that no special gene mapping methods and electron microscopes are needed, because these changes are already visible in an ordinary light microscope. They consist, inter alia, on the breakage of a chromosome and loss of the broken fragment, or its transfer to another chromosome. Another example is the reversal of a chromosome fragment between two break points, or the creation of a ring chromosome structure after a chromosome break, instead of the correct four-arm structure. The examples given are examples of structural chromosome aberrations. Numerical aberrations consist of the addition or loss of one, less often two whole chromosomes, or the addition of a whole set of 23 chromosomes from one of the parents.

The occurrence of genetically determined diseases is not very rare. It should be remembered that hereditary disorders do not have to be visible at first glance – mutations can cause disturbances in the functioning of the body, and not only affect the appearance of the affected person. Sometimes, however, both features occur simultaneously.

Along with the development of medicine and genetics, in addition to trying to prevent or improve the quality of life of sick people, great importance was also attached to genetic counseling. It is a form of specialist medical aid, the purpose of which is, among others, providing the consulted family with all information, calculating the so-called genetic risk, but also providing support and objective support to the family in making future decisions. The genetic counseling team should consist of a specialist, a person providing genetic counseling – in Poland these two “positions” are connected by a physician specializing in genetics – and the so-called support. These can be psychologists, people from lay or religious support groups, or social workers.

The patient should be examined by the attending physician. It is also important to examine relatives of the patient who do not have symptoms of the disease in order to exclude mild forms of the disease with abortive, hardly noticeable symptoms. It is also necessary for the family to fully cooperate in supplementing the pedigree data. The analysis of pedigree makes it possible to determine the course of transmission of a given feature – a mutation, as well as to determine which members of the family being consulted bear the highest genetic risk and how extensive research should be planned in a given family.

The principle professed by the vast majority of people providing genetic counseling is the view that patients’ decisions regarding pregnancy planning, acceptance of prenatal tests, termination of pregnancy after detection of a defect in the fetus, and possible adoption should be made by the consulted persons themselves in accordance with their knowledge, worldview, life goals, system of values ​​or beliefs.

The most important indications for genetic counseling are:

– advanced maternal age (prenatal diagnosis is offered to pregnant women aged 35 or older)

– known or suspected hereditary diseases in the family

– a fetus or a child with single or multiple birth defects

– a child with a mental retardation

– recurrent spontaneous miscarriages

– exposure to substances with known or suspected harmful effects on the fetus

– kinship of parents

Text: lek. med. Roma Roemer-Ślimak