Fundamentals of Medical Genetics - Buzhyievska T.I. 2001

General Genetics
Variability of Living Organisms

The Variability of living organisms can be heritable and non-heritable. According to C. Darwin, non-heritable variability is referred to as "definite variability," or more commonly as modificational variability, or simply modifications. In other words, it is the variability of an Organism's phenotype (without altering the genotype) within the Structure/21.html">Limits of the reaction norm predetermined by a specific genotype. Modifications include both adaptive changes that arise in numerous individuals and, in most cases, are reversible, disappearing once the triggering factor ceases to act. These changes are specific to the factor itself. The primary mechanism underlying modifications is based on alterations in Gene Expression regulation. The most persistent (prolonged in time) modifications are so-called morphoses, which occur during Embryogenesis and persist throughout the organism's life. Morphoses do not disappear when the inducing factor is removed; they are irreversible because the Stages of Ontogeny and the timing of their occurrence are irreversible. Human teratogenesis also belongs to this type of variability. However, in some cases, ontogenetic variability is accompanied by modifications of the cellular genetic program. Today, the term "epigenetic variability" is being introduced, which can be heritable.

S.G. Inge-Vechtomov (1989) classifies the variability of organisms as follows: heritable — combinative and mutational; non-heritable — modificational; ontogenetic (prolonged modifications, teratogenesis, morphoses), which exhibits features of both heritable and non-heritable variability.

Heritable variability — indefinite («sports» according to C. Darwin) — is mutational variability that arises As a result of The formation of new variants of genetic material. These are changes within a gene (allelic variants), a chromosome, or The Genome. Consequently, a distinction is made among gene, chromosomal, and genomic Mutations. Such changes may occur in somatic Cells, which, if inherited, leads to a clone of mutant body cells, or in germline cells, potentially producing mutant offspring. Based on their phenotypic expression, mutations can be lethal, sublethal (reducing organism fertility and viability), neutral, or even confer a selective advantage to their carriers under certain environmental conditions (increasing fertility and viability).

Mutational variability arises, much like modificational variability, under the Influence of Environmental factors—specifically those that damage the genetic program either directly or indirectly via endogenous stress mechanisms. Depending on their causes, mutations are classified as spontaneous (the exact cause is unknown, but inevitably exists) and induced by physical, chemical, or biological factors. A special place among Biological Mutagens is occupied by Viruses, live viral Vaccines, and recombinant DNAs used in the fields of biotechnology, Introduction/32.html">Genetic Engineering, and Gene Therapy. Such components (informational molecules) are capable of inducing specific (selective) mutations associated with The Nature and degree of complementarity of these molecules to the recipient's genetic program. Such DNA or RNA carriers can induce prolonged mutagenesis, epigenetic heritable variability, act as Mobile Genetic Elements that selectively integrate into the genome or are eliminated, change their localization, and so forth.

Physical Mutagens (UV irradiation, radiation) and Chemical Mutagens (which are more potent and dangerous; some are known as supermutagens) act nonspecifically, damaging mutable Regions of the genome.

Mutational variability serves as the basis for another type of heritable variability — combinative variability, which ensures organismal diversity within a species and, together with mutational variability, creates the conditions for evolution. One of the mechanisms of combinative variability is sexual reproduction, which involves the recombining of genes and Chromosomes containing different alleles, alongside the correction of program errors during Meiosis (S.M. Gershenzon, 1996).

It is precisely during this period that modificational Changes in the genetic material of Germ Cells (epigenetic changes) occur, known as imprinting. The significance and mechanisms of this process are still not sufficiently understood.

Variability in organisms is as essential for The Development of life as heredity is for its preservation.

Knowledge of general genetics is essential for understanding The Essence of medical genetics, studying the Basic patterns of origin and inheritance of human pathology, and developing new Methods for the Diagnosis, Treatment, and Prevention of diseases based on their biological nature, Etiology, and a deep understanding of pathogenetic mechanisms.

Medical genetics is the science of Hereditary diseases that also takes into account hereditary predisposition. Because an organism's genetic features exist from the moment of Fertilization, a knowledge of medical genetics is particularly crucial for obstetrician-gynecologists, neonatologists, and pediatricians who stand at the dawn of new life. Pathology of the genetic material accounts for at least 50% of miscarriages, 25% of Congenital Malformations, 15% of perinatal mortality, and 10% of live-born children have hereditary defects. The proportion of hereditary pathologies among all human diseases is constantly increasing—on the one hand, due to successes in combating infections, toxic injuries, and trauma, and on the other hand, through the deepening of our knowledge in the field of genetics. Today, it can be confidently stated that there is no pathology in the development of which heredity does not play a role, just as, incidentally, there is no such thing as absolute physiological norm or absolute health.

S.G. Inge-Vechtomov (1989) classifies the variability of organisms as follows: heritable — combinative and mutational; non-heritable — modificational; ontogenetic (prolonged modifications, teratogenesis, morphoses), which exhibits features of both heritable and non-heritable variability.

Heritable variability — indefinite («sports» according to C. Darwin) — is mutational variability that arises as a result of the formation of new variants of genetic material. These are changes within a gene (allelic variants), a chromosome, or the genome. Consequently, a distinction is made among gene, chromosomal, and genomic mutations. Such changes may occur in somatic cells, which, if inherited, leads to a clone of mutant body cells, or in germline cells, potentially producing mutant offspring. Based on their phenotypic expression, mutations can be lethal, sublethal (reducing organism fertility and viability), neutral, or even confer a selective advantage to their carriers under certain environmental conditions (increasing fertility and viability).

Mutational variability arises, much like modificational variability, under METABOLISM/18.html">The Influence of environmental factors—specifically those that damage the genetic program either directly or indirectly via endogenous stress mechanisms. Depending on their causes, mutations are classified as spontaneous (the exact cause is unknown, but inevitably exists) and induced by physical, chemical, or biological factors. A special place among biological mutagens is occupied by viruses, live viral vaccines, and recombinant DNAs used in the fields of biotechnology, genetic engineering, and gene therapy. Such components (informational molecules) are capable of inducing specific (selective) mutations associated with the nature and degree of complementarity of these molecules to the recipient's genetic program. Such DNA or RNA carriers can induce prolonged mutagenesis, epigenetic heritable variability, act as mobile genetic elements that selectively integrate into the genome or are eliminated, change their localization, and so forth.

Physical mutagens (UV irradiation, radiation) and chemical mutagens (which are more potent and dangerous; some are known as supermutagens) act nonspecifically, damaging mutable regions of the genome.

Mutational variability serves as the basis for another type of heritable variability — combinative variability, which ensures organismal diversity within a species and, together with mutational variability, creates the conditions for evolution. One of the mechanisms of combinative variability is sexual reproduction, which involves the recombining of genes and chromosomes containing different alleles, alongside the correction of program errors during meiosis (S.M. Gershenzon, 1996).

It is precisely during this period that modificational changes in the genetic material of germ cells (epigenetic changes) occur, known as imprinting. The significance and mechanisms of this process are still not sufficiently understood.

Variability in organisms is as essential for the development of life as heredity is for its preservation.

Knowledge of general genetics is essential for understanding the essence of medical genetics, studying the basic patterns of origin and inheritance of human pathology, and developing new methods for the diagnosis, treatment, and prevention of diseases based on their biological nature, etiology, and a deep understanding of pathogenetic mechanisms.

Medical genetics is the science of hereditary diseases that also takes into account hereditary predisposition. Because an organism's genetic features exist from the moment of fertilization, a knowledge of medical genetics is particularly crucial for obstetrician-gynecologists, neonatologists, and pediatricians who stand at the dawn of new life. Pathology of the genetic material accounts for at least 50% of miscarriages, 25% of congenital malformations, 15% of perinatal mortality, and 10% of live-born children have hereditary defects. The proportion of hereditary pathologies among all human diseases is constantly increasing—on the one hand, due to successes in combating infections, toxic injuries, and trauma, and on the other hand, through the deepening of our knowledge in the field of genetics. Today, it can be confidently stated that there is no pathology in the development of which heredity does not play a role, by the way, just as there is no such thing as an absolute norm or absolute health.