MEDICAL BIOLOGY, ANATOMY, HUMAN PHYSIOLOGY AND PATHOLOGY - Ya.I. Fedoniuk 2010

BIOLOGY

CHAPTER 1. BIOLOGICAL BASES OF HUMAN VITAL ACTIVITY

1.4. ONTOGENETIC LEVEL OF LIFE ORGANIZATION

1.4.2. Basics of Human Genetics

Twin Method

This method was proposed in 1875 by F. Galton. The Essence of the twin method lies in comparing studied traits across different groups of twins, based on the similarities or differences of their genotypes and the environment in which they grew up. Twins are defined as offspring of the same mother who developed together and were born in the course of the same delivery. They can be monozygotic (MZ) or dizygotic (DZ). Monozygotic (identical) twins develop from a single zygote As a result of its division into 2, 3, or more embryos; they have identical genotypes (100% of identical genes), are always of the same sex, and are extremely similar to each other. Dizygotic (fraternal, non-identical) twins develop during a single Pregnancy from different zygotes (from two or more ova fertilized by different spermatozoa); they can be of the same sex or different sexes; they share approximately 50% of identical genes and are no more similar to each other than siblings born at different times. The birth rate of twins in various countries is approximately 1 per 86–88 deliveries. Monozygotic twins are born less frequently than dizygotic ones. On average, there is one pair of MZ twins for every 2–3 pairs of DZ twins. Dizygotic twins are more frequently born to women who have undergone gonadotropic hormone therapy, as well as to women aged 40–45. The predisposition to having twins is inherited through the maternal line.

The twin method is most commonly used to: 1) assess the relative roles of HEREDITY AND ENVIRONMENT in The Development of a trait (disease); 2) establish the hereditary nature of a trait; 3) determine Gene expressivity and penetrance; 4) determine the effectiveness of external factors' influence on the Organism, such as therapeutic agents, upbringing, and education.

When applying this method, comparisons are made between: 1) monozygotic and dizygotic twins; 2) partners of monozygotic pairs with each other; 3) twin analysis data and the general population.

To determine the zygosity (mono- or dizygosity) of twins, A number of Methods have been proposed: 1) the polysymptomatic method—study of phenotypic symptoms (pigmentation of Hair, eyes, and Skin, hair shape and hair cover features, shape of the Nose, Lips, and auricles, digital patterns); 2) portrait identification; 3) the questionnaire method (the questionnaire contains 12 questions for the twins and 4 for the parents); 4) immunological methods. The method that can establish zygosity with 100% reliability

—is a skin graft. Good engraftment indicates monozygosity, while rejection

—indicates dizygosity. Modern Methods for determining zygosity are molecular-genetic.

To determine The Role of the genotype or environmental conditions in the development of a trait, the concordance (discordance) of partners for specific traits is compared. A twin pair is called concordant if the studied trait appears in both partners, and discordant if the studied trait is present in only one of them. The higher the concordance, the greater the role played by heredity in the Development of the trait. Traits such as eye and hair color, and Blood Groups are completely determined by the genotype (Table 1.10).

Class="center">Table 1.10

Concordance of certain human traits in monozygotic (MZ) and dizygotic (DZ) twins.

Similar concordance values in pairs of mono- and dizygotic twins indicate the predominant importance of environmental factors in the development of a trait, as occurs with certain infectious diseases whose contraction depends on contact with the causative agent (e.g., measles). Since monozygotic twins have identical genotypes, phenotypic differences between them are explained by environmental factors. Dizygotic twins allow for the analysis of another scenario: environmental conditions are the same, while the genotypes of the twins differ.

The degree of concordance makes it possible to determine The Nature of a disease (whether it is hereditary or non-hereditary). For instance, studying the inheritance of Down syndrome showed the following: if one of the monozygotic twins had Down syndrome, the other twin had it as well. In dizygotic twins, typically only one was affected while the other remained healthy. Later, cytological studies proved that Down syndrome is associated with A change in the genotype, meaning it has a hereditary nature.

To quantitatively assess the role of heredity in the development of a studied trait (disease), the heritability coefficient is calculated using the formula proposed by the German geneticist K. Holzinger (1929):

The heritability coefficient (H) is expressed as fractions of a unit or as a percentage. If the coefficient

where H is the heritability coefficient, CMZ is the concordance of monozygotic twins (%), and CDZ is the concordance of dizygotic twins (%).

If the concordance of monozygotic twins is equal to 1 (100%), then regardless of the concordance of dizygotic twins, the heritability coefficient is also equal to 1, meaning that the manifestation of the trait is entirely determined by the genotype. Conversely, if the concordance of monozygotic twins is less than 1, the heritability coefficient decreases as the difference in concordance between mono- and dizygotic twins gradually increases. When the concordance of mono- and dizygotic twins is equal, the heritability coefficient is zero, meaning that the realization of the trait is completely determined by environmental factors.

The twin method is complex, labor-intensive, and time-consuming, but effective and objective, which is why it finds application in MEDICAL Genetic Counseling and Pharmacogenetics.