MEDICAL GENETICS

Introduction
Classification of hereditary diseases Lecturer: Meerim Kurmanalieva
 MEDICAL GENETICS
• Medical genetics is a field of medicine, a science that studies the
phenomena of heredity and variability in different populations of people,
the peculiarities of the manifestation and development of normal and
pathological signs, the dependence of diseases on genetic predisposition
and environmental conditions.
 MEDICAL GENETICS
• Medical genetics is an integral part of human genetics. it studies the laws
of heredity and variability from the point of view of human pathology. A
special section of medical genetics is clinical genetics, which studies the
issues of pathogenesis, clinic, diagnosis, prevention and treatment of
hereditary diseases.
 THE TASKS OF MEDICAL
GENETICS
1) Study of the role of genetic and external factors in the development of hereditary
pathology
2) Study of the nature of inheritance and the manifestation of pathological genes
3) Development of the principles of classification, diagnosis, and prevention of
hereditary diseases
4) Study of the nature of hereditary pathology at the molecular, cellular, organizational
and population level
 THE TASKS OF MEDICAL
GENETICS
5) Identification of the spread of hereditary diseases and congenital malformations
6) Improvement of genetic engineering methods for the purpose of gene therapy and
obtaining new medicinal substances.
7) Wide and widespread introduction of medical and genetic counseling
8) Development of methods for the prevention of hereditary diseases
 THE HISTORY OF GENETICS
The history of genetics can be conditionally divided into three main periods:
1. The period of classical genetics (1900 -1930).
• During this period, the theory of the gene, the chromosomal theory of heredity was
created,
• the doctrine of the interaction of genes, phenotype and genotype was developed.
 THE HISTORY OF GENETICS
2. The period of neoclassical genetics (1930-1953).
• During this period the possibility of artificially obtaining changes in genes and
chromosomes (experimental mutagenesis) was discovered;
• it was found that a gene is a complex system that is fragmented into parts;
• the principles of genetics were substantiated populations and evolutionary genetics;
• biochemical genetics was created and it was proved that DNA molecules are the
basis for recording genetic information.
 THE HISTORY OF GENETICS
3. The period of synthetic genetics (from 1953 to the present).
• In 1953 biochemist James Watson and biophysicist Francis Crick at Cambridge
University, UK were awarded the Nobel Prize for their efforts to demonstrate the
instantly known double-helix structure of DNA.
 THE HISTORY OF GENETICS
• In this period it is shown genetic significance;
• the exact number of chromosomes in humans arose a new discipline of clinical cytogenetics;
• received further the development of the theory of gene and mutations;
• The new data in the field biochemical, evolutionary, environmental, immunological, cancer
genetics;
• created by recombinant DNA technology (genetic engineering).
• the biological properties of a person during this period become central the object of genetic
research.
• their combination with molecular genetics and molecular medicine provided a synthetic
approach to the problem of heredity.
 THE HISTORY OF GENETICS
• Modern genetics closely interacts with the fundamental sciences:
• physics,
• chemistry,
• mathematics,
• biology,
• ecology and other sciences.
 THE HISTORY OF GENETICS
• Due to this relationship, in the middle of the last century, such independent
specialized sections of genetics as:
• human genetics,
• population genetics,
• cytogenetics,
• immunogenetics,
• oncogenetics,
• pharmacogenetics
• HUMAN GENOME PROJECT created.
 THE HISTORY OF GENETICS
• Relatively recently, such concepts and terms as:
• the genome,
• molecular cytogenetics,
• environmental genetics,
• and molecular medicine began to enter the everyday life.
 THE CAUSE OF HEREDITARY
DISEASES
• Hereditary diseases are diseases, the occurrence and development of which is
associated with various defects and disorders in the hereditary apparatus of cells.
• Hereditary diseases can be caused by mutations transmitted in families by
inheritance, or mutations that have re-emerged in the cells of the germ line, in the
zygote or at very early stages of embryo development. Hereditary diseases are
numerous (more than 6000 are known) and diverse in their manifestations.
• Some hereditary diseases are congenital.
• Congenital hereditary diseases should be distinguished from malformations
caused, for example, by infection (syphilis or toxoplasmosis) or the impact of other
damaging factors on the fetus during pregnancy.
 CLASSIFICATION OF
HEREDITARY DISEASES
Hereditary diseases are based on mutations:
• chromosomal
• gene
• mitochondrial
 GENE

• A genetic disorder is a disease caused in

whole or in part by a change in the DNA
sequence away from the normal sequence.
 CHROMOSOMAL

• Chromosomal disorder, any syndrome

characterized by malformations or
malfunctions in any of the body's systems,
and caused by abnormal chromosome
number or constitution.
 MITOCHONDRIAL

• Mitochondrial diseases are chronic (long-

term), genetic, often inherited disorders that
occur when mitochondria fail to produce
enough energy for the body to function
properly. (Inherited means the disorder was
passed on from parents to children.)
 CLASSIFICATION OF
HEREDITARY DISEASES
Hereditary diseases are also classified according to the type of inheritance. For a
significant part of hereditary diseases, the type of inheritance is established —
pathological signs, as well as normal ones, can be inherited.
Types of inheritance:
• Autosomal dominant
• autosomal recessive
• sex-linked
TYPES OF INHERITANCE
TYPES OF INHERITANCE
 TYPES OF INHERITANCE
• The term " autosomal "indicates that the mutant gene is localized in the autosome," X-
linked "— in the sex X chromosome, and "Y-linked" - in the sex Y chromosome. The
separation of dominant and recessive types of inheritance is significant from a medical point
of view, since with the dominant type of inheritance, the clinical manifestation of the disease
is found in homo - and heterozygotes, and with recessive — only in homozygotes, that is,
much less often. The main methods by which a particular type of inheritance is established
are clinical and genealogical, based on the analysis of pedigrees, and more accurate
segregation analysis, the object of which, as a rule, are the so — called "nuclear families"
(that is, parents and children).
 DISEASES CAUSED BY NUCLEAR
DNA DEFECTS
Gene diseases associated with nuclear DNA point mutations:
1. Monogenic diseases associated with nuclear DNA mutations;
2. Polygenic diseases associated with nuclear DNA mutations.
3. Chromosomal diseases:
a)Related to changes in the structure of chromosomes.
b)Related to changes in the number of chromosomes
• The first two groups are caused by point mutations of DNA (gene diseases),
• the third group corresponds to gross structural rearrangements of chromosomes
(chromosomal aberrations) or changes in their number.
 MONOGENIC DISEASES
• This is the widest group of hereditary diseases. Currently, more than 4,000 variants of
monogenic hereditary diseases have been described, the vast majority of which are quite rare
(for example, the frequency of sickle cell anemia is 1/6000).
• A wide range of monogenic diseases are formed by hereditary metabolic disorders, the
occurrence of which is associated with a mutation of genes that control the synthesis of
enzymes and cause their deficiency or structural defect — fermentopathy.
• Nuclear DNA point mutations can have one of three types of inheritance: autosomal
dominant, autosomal recessive, and sex-linked inheritance. The type of inheritance of a
mutation can be determined using genealogical research.
 CHROMOSOMAL DISEASES
• Chromosomal diseases are caused by gross
violations of the hereditary apparatus — a
change in the number or structure of
chromosomes.
• This includes Down's syndrome, Klinefelter,
Turner, Edwards, "cat's cry" and others.
CHANGE IN THE NUMBER OF
CHROMOSOMES
TRISOMY #21
CHANGE IN THE STRUCTURE OF
CHROMOSOMES
 POLYGENIC HEREDITARY
DISEASES
• Polygenic diseases are inherited difficult. For them, the issue of inheritance cannot be
resolved on the basis of Mendel's laws. Previously, such hereditary diseases were
characterized as diseases with a hereditary predisposition. However, now we are talking
about them as multifactorial diseases with additive-polygenic inheritance with a threshold
effect.
• These diseases include such diseases as cancer, diabetes mellitus, schizophrenia, epilepsy,
coronary heart disease, hypertension and many others.
 DISEASES CAUSED BY
MITOCHONDRIAL DNA DEFECTS

• Gene diseases associated with mtDNA point

mutations.
• Diseases caused by gross structural disorders
of mtDNA
 DISEASES CAUSED BY
MITOCHONDRIAL DNA DEFECTS
• Mitochondrial DNA (mtDNA) is inherited through the maternal line. Pathological disorders
of cellular energy metabolism caused by mtDNA mutations can manifest themselves as
defects of various links in the Krebs cycle, in the respiratory chain, beta-oxidation processes,
etc.
• Due to heteroplasmia, the manifestation and severity of diseases caused by similar mtDNA
disorders may be different in different people, depending on the ratio of mutant and normal
mitochondria in the cytoplasm of cells.
 GENE DISEASES ASSOCIATED
WITH MTDNA POINT MUTATIONS
• There are a number of monogenic diseases associated with point defects of mitochondrial
genes:
• Leber's hereditary optical neuropathy is caused by a missense mutation in one of the
eighteen genes encoding oxidative phosphorylation proteins;
• the disease of myoclonal epilepsy and rough-red fibers (MERRF) is caused by a point
replacement in the tRNA gene;
• the syndrome of mitochondrial encephalomyopathy and stroke-like episodes (MELAS) also
develops due to a point replacement in the tRNA gene
 STATISTICS OF DISEASES
CAUSED BY GENETIC
DISORDERS
• Approximately 5-6 children out of 100 are born with some genetically determined diseases.
In most cases, these are diseases with genetic predispositions. These may be developmental
defects, disorders in the intellectual development of the child. These 5-6 percent include
hereditary diseases that occurred for the first time or inherited from one of the parents.
Thank you for attention!