One gene = One disease

When we think of genetic diseases, we think of a complex jumble of scientific terms, molecular processes, and difficult explanations that we only vaguely understand. However, sometimes the development of a genetic disease depends solely on the failure (mutation) of the genetic code of a single gene. These types of diseases are known as monogenic diseases. But how are these diseases transmitted between different generations? The following classification will help us better understand.

Inheritance pattern of diseases

The different inheritance patterns of monogenic diseases can be:

• Autosomal dominant inheritance: A single mutated copy of the gene will cause a person to develop the disease. We know that if a parent has this mutated copy, they will pass it on to their offspring, and their child will also be affected, so they are easy to prevent and diagnose.
• Autosomal recessive inheritance: Two mutated copies of the gene are required to manifest the disease. In the case of a single mutated copy, the individual does not present the pathology, but does transmit it to offspring. For this reason, in this type of disease, the following are of particular importance: genetic tests carrier screening, which will allow parents to know if they are at risk of their child inheriting two mutated copies of the gene that causes the disease.
• X-linked dominant inheritance: With only one mutated copy of the X chromosome, women develop the disease. On the other hand, since men only have one X chromosome, the presence of these mutations will always be an indicator of the disease. It is also important to keep in mind that fathers with these types of mutations will only pass them on to their daughters, since they are the ones who inherit the paternal X chromosome.
• X-linked recessive inheritance: Two mutated copies of the X are necessary for women to develop the disease. Therefore, if they have a single mutated allele, they will be carriers of the disease, but will not manifest it. However, if women pass the mutation on to their sons, they will have the disease because, as mentioned above, they only have one X chromosome.
• Y-linked inheritance: It only affects men, since women do not have a Y chromosome. Furthermore, men with mutations in this chromosome will transmit the genetic alteration to their offspring as long as their children are male, therefore, they will never transmit it to their daughters.

Examples of monogenic diseases

There are more than 10,000 monogenic diseases currently classified, although some are better known to the general public than others. Under this criterion, we can highlight two: cystic fibrosis and sickle cell anemia.

Cystic Fibrosis

It is a disease of autosomal recessive inheritance caused by an alteration in the CFTR gene, located on chromosome 7 (7q31). This gene encodes the CFTR protein, which forms the ion channels for calcium (Ca ²⁺ ), chloride (Cl ^– ), potassium (K ⁺ ) and sodium (Na ⁺ ), on the epithelial surfaces of the body. It is also responsible for the transport of energy, in the form of ATP, through intracellular membranes. The most frequent mutation, occurring in approximately 70% of people with cystic fibrosis, is the deletion of phenylalanine at position 508, generating a non-functional protein.

In good health, the CFTR protein provides the ionic balance necessary for the formation of a thin mucus layer that protects the lungs from infection by microorganisms. However, a mutation in this gene affects the epithelium of the respiratory tract and the lining of the intestines, genitals, pancreas, bile ducts, and sweat glands, hindering the transport of ions across the membrane and generating a thick mucus that clogs and obstructs the internal ducts and the normal function of these organs.

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Thus, cystic fibrosis causes respiratory problems such as chronic pneumonia, weight loss, delayed growth and development, difficulty excreting feces, and infertility. Given this prognosis, it is highly recommended to use Genetic tests for the diagnosis of cystic fibrosis , with the aim of improving the treatment and prognosis of these complications.

Sickle cell anemia

It is an inherited disease Autosomal recessive and monogenic , caused by a mutation affecting the HBB gene, which encodes the protein that provides reddish pigmentation to red blood cells and is also essential for transporting oxygen in the blood: hemoglobin. The most common mutation is the substitution of the amino acid glutamate for the amino acid valine, a change that results in hemoglobin with a defective molecular structure, which in turn causes the red blood cells to appear sickle-shaped, hindering blood flow and causing blood clots or vascular problems.

In this context, the main problems that a person with sickle cell anemia These are caused by the clotting of red blood cells in the blood vessels, such as cerebrovascular accidents, lung infections, high blood pressure in the lungs, blindness, ulcers, nerve and organ damage due to lack of oxygen, high levels of bile deposits, or problems during pregnancy due to the formation of clots, among others.

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On the other hand, carrier patients who have a single copy of the mutated HBB gene have half of their red blood cells normal and the other half sickle-shaped. In this situation, patients do not present acute symptoms, but they are carriers of the disease. A curious fact about this disease is that in African populations, heterozygous individuals who have one normal allele and one mutated allele have an evolutionary advantage over those who have two normal copies, and the former are less likely to suffer from it. malaria , caused by infection with Plasmodium falciparum , which requires functional red blood cells to complete its life cycle.

Cystic fibrosis and sickle cell anemia are just two examples of the large number of monogenic diseases currently described that can be easily diagnosed using genetic testing. This is yet another reason why we believe that clinical genetics is undoubtedly here to stay.