1. Introduction to medical genetics.
Pedigree chart. Genetic,
multifactorial disorders.
Lecturer: Temirova Meerim
2. Lecture plan
• 1. Subject and tasks of human genetics.
• 2. Methods of human genetics.
• 3. Medical genetics - subject and objectives.
• 4. Hereditary diseases - etiology, diagnosis,
principles of correction.
• 5. Medical genetic counseling.
5. The tasks of human genetics
• 1. Study of the organization of the human genome.
• 2. Study of the structure of human genes.
• 3. Study of the mechanisms of the implementation of
genetic information.
• 4. Study of the patterns of inheritance of traits in
humans.
• 5. Study of the patterns of variability in humans.
• 6. Study of the action of genes in onto- and
phylogenesis.
• 7. Study of the genetic structure of human
populations and their dynamics.
• 8. Solving the problems of medical genetics.
6. Difficulties in conducting genetic
analysis in humans
• 1.The impossibility of conducting experimental
• crossbreeding.
• 2.Long term of generation change (25-30 years).
• 3.Long pre-reproductive period.
• 4. A large number of clutch groups.
• 5. A small number of children in the family.
• 6. Inability to obtain induced mutations.
• 7. Social inequality of people.
7. Methods of human genetics
• 1.Genealogical method.
• 2. The twin method.
• 3.Cytogenetic method.
• 4. Biochemical method.
• 5. Population-statistical method.
• 6. Method of genetics of somatic cells.
• 7. Modeling method.
• 8. Molecular genetic method.
• 9. Experimental method.
8. Genealogical method
The genealogical method is based on
compilation and analysis of pedigrees.
Pedigree is a graphical representation of
family ties or clans.
When compiling pedigrees, certain
symbols are used.
13. Characteristics of an autosomal
dominant type of inheritance
1. The symptom occurs with the same
frequency in men and women.
2. The trait is passed from parents to
children from generation to generation
(vertical inheritance).
3. Patients are found in every generation,
but there may be breakthroughs (with
incomplete penetrance of the dominant
gene).
15. Autosomal recessive inheritance
1. Men and women are affected from the same
frequency.
2. Parents of sick offspring are healthy.
3. Among the parents of the proband is noted
high frequency of consanguineous marriages.
4. As a rule, among consanguineous (children
of one father from different mothers) or uterine
(children of one mother from different fathers).
The disease does not manifest itself in eve and
sisters.
17. Recessive X-linked inheritance
1. The disease manifests itself almost exclusively
in men.
2. A son never inherits a mutant trait from his
father.
3. Men, relatives of Praband from the mother's
side, his brothers and grandmother's brothers
from the mother's side were struck.
4. If a proband is a woman, then her father and
all her sons will surely go.
5. Half of the Prband brothers are amazed, half
are healthy.
19. Dominant X-linked inheritance
1. Women are affected 2 times more often
than men, but they get sick more easily.
2. A proband usually has one of the
parents.
3. Disease from a sick mother with equal
daughters and sons inherit with the greatest
probability.
4. Illness from a sick father is always
passed on to daughter, but not to son.
20. Twin method
Examines genetic patterns on
twins in order to identify correlations
the role of heredity and environment
in the development of signs.
Stages:
Twin sampling.
Diagnostics of the zygosity.
Analysis of intrapaired similarity of
monozygotic and dizygotic twins.
24. Twin method
Twin phenotypic similarities
couples are called concordance.
С
С + D
C – number of concordant pairs
D – number of discordant pairs
The paired concordance coefficient is
the ratio of the number of concordant pairs to the total
the number of concordant and discordant pairs.
It is expressed in unit fractions or percentages.
C
25. Twin method
To determine the relative role of heredity and
environment in determination traits use
Holzinger's formula.
Н
Cmz- C dz
1 - C dz
Е = 1 - Н
Е + Н = 1
26. Concordance in terms of morbidity in
twins (in%).
Diseases MZ
Twins
DZ
Twins
Schizophrenia 67,0 12,1
Affective insanity 73,1 15,2
Epilepsy 60,8 12,3
Hare lip 33,0 5,0
Congenital dislocation of the hip 41,4 2,8
Congenital pyloric stenosis 66,7 3,4
Measles 97.4 95,7
Chickenpox 92,8 89,2
27. Cytogenetic method
The cytogenetic method is based on microscopic
examination of chromosomes.
Tasks:
1. Study of the morphology of chromosomes.
2. Study of the normal polymorphism of
chromosomes.
3. Study of the mutation process.
4. Drawing up cytogenetic maps of
chromosomes.
5. Diagnosis of chromosomal diseases.
31. POPULATION - STATISTICAL METHOD
The method is used to study hereditary traits.
in human populations.
The fundamentals of the method were developed by Hardy and Weinb
The object of the research is human populations.
In human genetics, a population is considered a group of people
taking the same territory and freely entering into marriage.
Small populations:
1 - isolates - no more than 1500 people;
2 - demos - number of people from 1500 to 4500.
The characteristic features of human populations are:
a) the tendency towards their numerical growth;
b) reducing the pressure of natural selection.
32. Objectives of the method:
1 - determination of the frequencies of genes in the population;
2 - determination of the genetic structure of the population
and its dynamics;
3 - study of the mutational process;
4 - studying the role of heredity and environment in
the formation of phenotypic polymorphism
according to normal signs:
5 - study of the role of heredity and the environment in the
no diseases, especially with hereditary
nym predisposition;
6 - study of the role of genetic factors in anthropo-
genesis.
POPULATION - STATISTICAL METHOD
33. POPULATION - STATISTICAL METHOD
Hardy-Weinberg's law.
pA is the frequency of the dominant allele
of the gene in the population;
qa is the frequency of the recessive allele
of the gene in the population;
рА + qа = 1 - population gene pool.
The integrating factor of the gene pool, which forms
the genetic structure of the population is
panmixia:
(pA + qa) x (pA + qa) = p2AA + 2pqAa + q2aa
According to Hardy-Weinberg's law, in ideal ass
changes in the frequency of genes and genotypes when
changing generations
constant.
34. Ideal population
Ideal population properties:
1 - large number (at least 500 individuals);
2 - no mutation process;
3 - the same vitality homo - and
heterozygotes;
4 - panmixia.
35. BIOCHEMICAL METHOD
1.Studies the structure of proteins and their
role in the formation of traits.
2. Explores protein polymorphism
in human populations.
3. Used in the diagnosis of gene
diseases.
42. Somatic cell hybridization method (localization of
the human thymidine kinase gene)
М – клетки мыши дефицитные по тимидинкиназе(ТК-)
Н – нормальные клетки человека (ТК +)
17 хромосома человека
45. Medical genetics studies hereditary
human pathology.
She solves the following tasks:
1.Explores the causes (etiology) of hereditary
diseases.
2.Studies the pathogenesis (mechanisms) of hereditary
diseases.
3.Studies the clinical manifestations of hereditary
diseases.
4.Develops methods for the diagnosis of hereditary
noisy pathology.
5. Develops methods of correction (treatment)
hereditary diseases.
6. Develops methods of prevention of inherited
natural diseases.
51. Chromosomal diseases
Chromosomal diseases are a large group of clinically
different pathological conditions caused by
chromosomal or genome
new mutations.
The nature and severity of the manifestation of
chromosomal diseases varies depending on the type of
mutation and chromosome.
Common to all forms of chromosomal diseases is the
multiplicity of lesions: craniofacial dysmorphia,
congenital malformations of internal and external
organs, developmental and growth retardation, mental
development disorders, endocrine disorders.
52. Down Syndrome
Trisomy 21 (trisomy G)
Karyotype 47, + 21;
Translocation option
Karyotype 46, t 21 15
Frequency 1: 800 - 1: 1000
External signs:
-mongoloid eye section;
-epicant; short nose with shi
a rocky bridge of the nose; semi-
covered mouth with protruding
tongue
com. Mental retardation.
Heart defects, immunodeficiency
56. Edwards syndrome
Trisomy 18 (trisomy E)
Described in 1960.
Karyotype 47, + 18.
Frequency: 1: 7000.
External signs:
dolichocephaly, microstomy,
micrognathia, deformation
of the auricles.
Severe mental retardation,
heart defects, heterotopia
in the cerebellum.
In girls, 3 times more often.
58. Patau Syndrome
Trisomy 13 (trisomy D)
Chromosomal etiology was
established in 1960 by K. Patau.
Karyotype 47, + 13.
Frequency: 1: 14500.
External signs:
microphthalmia, cleft palate,
deformation of the ear
covines. Six-fingered with
sides of the little fingers
and toes.
mental retardation, heart defects,
hypoplasia of the cerebellar
vermis.
Arineencephaly. Deafness.
60. Shereshevsky-Turner syndrome
Monosomy-X.
Karyotype 45, X0
Frequency - 07: 1000
Described in 1925 by
N. Shereshevsky.
External signs:
- short stature, pterygoid
neck folds, wide nipples, wide
nose bridge, hypertelorism
arched palate.
Dysgenesis of the gonads,
primary amenorrhea, infertility.
Mental retardation.
63. Klinefelter's syndrome
Karyotype: 47, XXY
The frequency is 1: 500 –
1: 700 newborn boys.
Described in 1942
External signs:
-high growth; eunuchoid
body proportions, gynecomastia,
dysgenesis of the testicles. Oligo,
or azospermia. Lean hair.
65. Cat cry syndrome (Lejeune syndrome)
ч It develops with a deletion
of the short arm of
chromosome 5. Described
in 1963 by Lejeune.
Karyotype 46 XX, 5p-;
46 XY, 5p-.
Frequency 1: 45000
General developmental
delay, low birth weight,
characteristic crying
a child resembling
cat meow, microcephaly,
hypertelorism,
Erikantus.
bodyism
66. Multifactorial diseases.
Multifactorial or diseases with us-
icy predisposition are determined by
the combined action of hereditary
and external factors.
The hereditary predisposition to
disease is based on a wide genetic
human polymorphism. The predisposition
can be monogenic or polygenic
character.
68. Diseases with a hereditary
predisposition
The relative importance of heredity and environment
in the occurrence of multifactorial diseases
69. Methods for the diagnosis of hereditary
diseases
• 1.Genealogical method.
• 2. The twin method.
• 3.Cytogenetic method.
• 4. Biochemical method.
• 5. Population-statistical method.
• 6. Method of genetics of somatic cells.
• 7. Molecular genetic method.
70. Principles of the treatment of hereditary
diseases
• 1. Symptomatic treatment - the use of
drugs to alleviate the patient's condition.
• 2. Pathogenetic treatment - used to correct
metabolic disorders (the introduction of
active enzymes, hormones,
immunotherapy).
• 3. Etiotropic treatment - gene therapy -
correction of genetic defects in the somatic
cells of a sick person by introducing an
artificially created normal gene.
71. Medical genetic counseling
Medical genetic counseling is one of the types
specialized medical care,
the essence of which is to determine
the prognosis of the birth of a patient
th child, in explaining the probability
this event to the consultant and
help in making family decisions.
72. Stages of medical genetic
counseling
1.Clarification of the diagnosis of hereditary
diseases.
2. Determination of prognosis of offspring.
3. Giving a written opinion,
an oral explanation in an accessible
form of the meaning of genetic risk
and assistance to the family
in making a decision.
