Autosomal inheritance

Autosomal dominant inheritance

In autosomal dominant inheritance, the mutant gene acts aggressively and suppresses the healthy one. The disease is transmitted from generation to generation, which appears in the pedigree analysis as a vertical distribution pattern.

• Parents: As a rule, one of the patient's parents is affected. The only exceptions are cases where the pathology is the result of a de novo mutation (de novo).
• Offspring: The probability of an affected parent having an affected child is exactly 50%. This risk remains regardless of the child's sex or the number of births in the family.
• Healthy relatives: Unaffected family members have healthy offspring because they do not physically carry the mutant gene.
• Features: The incidence of the pathology in males and females is equal. At the same time, the severity and number of disease manifestations (expressivity) directly depend on environmental factors.

Examples of autosomal dominant pathologies

Typical diseases with this transmission mechanism include:

• Marfan syndrome;
• Huntington's chorea;
• Neurofibromatosis;
• Familial hypercholesterolemia;
• Hemoglobin M disease;
• Colon polyposis;
• Polydactyly.

Autosomal recessive inheritance pattern

For an autosomal recessive pathology to manifest, the mutant gene must be inherited from both parents simultaneously. In a pedigree, such diseases are distributed horizontally: they frequently occur in full siblings (siblings).

• Parents: The patient's parents are usually healthy but are carrier heterozygotes. The disease may unexpectedly appear in other relatives, such as first or second cousins.
• Clinical presentation: Symptoms of the disease are usually detected in childhood. In the homozygous state, the manifestations of the disease are more uniform due to high penetrance.
• Sex distribution: As with the dominant type, the incidence of the pathology in males and females is equal.
• Half-siblings: The disease is absent in half-siblings. Paternal half-siblings (children of the same father by different mothers) and maternal half-siblings (children of the same mother by different fathers) remain healthy.

Risk factor: consanguineous marriages

The occurrence of autosomal recessive diseases becomes significantly more likely in consanguineous marriages. The mechanism of this phenomenon is simple: such a union sharply increases the likelihood of two spouses meeting who are heterozygotes for the same pathogenic allele. Both spouses inherited this mutant gene from a common ancestor. On pedigree charts, a consanguineous marriage is indicated by a double line.

Examples of autosomal recessive pathologies

Among diseases with an autosomal recessive transmission mechanism are:

• Cystic fibrosis;
• Phenylketonuria;
• Galactosemia and glycogenoses;
• Oculocutaneous albinism;
• Adrenogenital syndrome (AGS);
• Chediak-Higashi syndrome;
• Hyperlipoproteinemias.

Pedigree analysis and symbols

Standard pedigree symbols are used to graphically represent inheritance (for example, when analyzing Marfan syndrome or cystic fibrosis):

• Square — male;
• Circle — female;
• Darkened circle or square — affected family member;
• Darkened symbol crossed out diagonally — deceased affected individual;
• Arrow — points to the proband (the individual from whom pedigree compilation begins).

Briefly: answers to topical questions

Class and exam questions

What else to study on this topic

• Concept of gene penetrance and expressivity
• Mechanisms of de novo primary mutations
• Features of homozygous and heterozygous carriage
• Rules for constructing a pedigree and taking a family history
• Impact of environmental factors on the severity of hereditary pathologies

Other topics in chapter "Chapter 3. Forms of pathology caused by changes in the genome"

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