Lect about hereditary disease

2. studies the role of a heredity in a pathology of
a person, law of transfer of hereditary illnesses
from generation to generation, develops the
methods of diagnostics, treatment and
preventive maintenance of a hereditary
pathology, including illnesses with hereditary
predisposition.

3. 1. What is the importance of hereditary factors in the
etiology of disease;
2. What is the ratio of hereditary and environmental
factors in the pathogenesis of the disease (both
hereditary and non-hereditary)?
3. What is the role of hereditary factors in the
detection of clinical symptoms of disease;
4. Does heredity affect on the recovery (of the
patient) and clinical outcome of the disease?
5. How does the heredity determine the specificity
of pharmacological and other treatments?

4. As the theoretical and clinical disciplines
medical genetics continues intensively
"expand" in different directions:
the study of the human genome,
cytogenetics, immunogenetics,
population genetics, clinical genetics.

12.  Family character disease
 Chronic, relapsing flow/course
 Specific symptoms of hereditary illnesses
 Plural pathological changes of bodies and
systems. ( because of pleiotropy– infulence of
one gene to the formation of several genes)
 "Resistency" to the most widespread methods
of therapy.

13. Classification of genetic disorders
1. Single gene (monogenic) disorders – caused by individual single gene
mutations, following classical Mendelian inheritance patterns.
2. Multifactorial disorders (olygogenic or polygenic) are not confined to any
specific pattern of single gene inheritance and are likely to be associated with
multiple genes effects together with the effects of environmental factors.
3. Chromosomal disorders – an excess or deficiency of the genes, contained in
whole chromosomes or chromosome segments (structural or numeral
chromosomal abnormalities).
4. Genetic diseases of somatic cells (cancer cells)
5. Mitochondrial disorders arise as a result of dysfunction of the mitochondrial
respiratory chain.

16.  Genealogical method - tracking the disease in
the family or a family with type of pedigree
links between members of the pedigree. In
medical genetics, this method is called
genealogical, because it is the observation of
pathological features with clinical
examination techniques.

18.  Gathering information about the family begins
with the proband. To obtain information about
relatives is a difficult task:
 ♥ First, not all patients know about diseases of
relatives
 ♥ second. They often hide familial cases
because of shame or on the contrary, “attribute"
to the relatives of the husband, trying to
"blame“ her husband in the origin of their
child’s illness.

20. Генеалогическое дерево больного Дарбыкеева Калыбека, 45 лет
1+1
I
II
III
IV
V
3+1
1 2 3 4 5 6 7 8 9 10 11
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23
V , 6 – пробанд
V , 8 – сибс пробанда
 – больные с миотонической
дистрофией

21.  ♥ The first task in the analysis of pedigree is
to establish/determine/find the hereditary
trait.

 ♥ The second problem, after the hereditary
trait of the desease is discovered, is to
establish the type of inheritance.

22. Types of
inheritance
А-D
Х-
linked
D
Y-
linked
Mitoch.
X-
linked
R
А-R

23. Characteristics of inherited pathology with autosomal
dominant type of inheritance:
 One of the parents is affected/ill
 disease occurs in every generation of pedigree, that is
the disease is transmitted down vertically
 proportion between affected and intact is
approximately 1:1
 Proportion of affected boys and girls is equal
 Affected women and men equally transmit the desease
to their children
 healthy children of affected parents have normal
children

24.  For many, autosomal dominant disorder is
characterized by considerable variability in
symptoms, not only between the families, but
also within the same family, to the point that the
mutant gene does not appear in the media. In
such cases, one can speak of penetrance and
expressivity.
 Penetrance is the frequency or probability of a
mutant gene. It is the percentage of individuals
in the population carrying the gene for which it is
manifested phenotypically.
 Expressivity (expressivness) is the degree of
phenotypic expression of genetically determined
trait. Therefore can not be considered a family
member is not affected, without further
investigation.

25. 
 Аа аа
 Аа Аа аа аа

26. Autosomal dominant pedigree

27. This type of inheritance manifests only at homozygotes.
Heterozygotes phenotypically don't differ from healthy people
with two normal allelles.
Characteristics of inherited pathology with autosomal-recessive type
of inheritance:
 parents usually are clinically normal
 the more the number of the children in the family, the more often
occur affected child
 the rarer the mutant gene in population, the more often there are
parental consanguinity
 if both husband and wife are affected, all children will be affected
 if one of the parents is affected, there will be healthy children (if
healthy spouse is not heterozygous);
 Both sexes are affected equally.
 Mendelian segregation corresponds to the ratio of offspring 1
(healthy): 2 (heterozygote): 1 (patient).

28.  Аа Аа
 АА Аа Аа аа

29. Peculiarities of this kind diseases inheritance are caused by
the fact that female has 2 X chromosomes and male has only
one X chromosome. The female who inherited pathological
allele from one of parents is heterozygote, male is
homozygote.
Characteristics:
 males and females are affected equally, but female more two
times then males
 affected females transmit pathological allele to 50% sons and
50% daughters
 affected male transmits pathological gene to all daughters
and does not transmit to sons, as far as sons inherit Y
chromosomes from their father
 on average females suffer less severe than males

30.  Хх ХУ
 ХХ ХУ хХ хУ

31. In this type of inheritance, females are often
heterozygotes, i.e. they are phenotyliccally healthy and
are carriers, -males are affected in any cases.
Characteristics:
this type of inheritance varies in accordance with
reproductive status. If the reproduction is damaged it
will be typical following:
 only males are affected
 approximately 23 cases are caused inheritance from
mothers-carriers, 13 cases
due to mutations in maternal X chromosome
 in inherited cases affected boys may have affected
brothers and uncles by their mother's side
 new mutations are sporadic cases or individual cases

32.  Хх ХУ
 ХХ ХУ хХ хУ

33.  Over a long period of time it was believed that Y
chromosome contains only heterochromatic sites
(without genes). Up-to-date researches revealed
and localized some genes in Y chromosome:
determining the development of testicles,
responsible for spermatogenesis, controlling
body's highs, limbs and teeth intensity,
determining auricles pylosis. The trait is
transmitted to all boys, naturaly/of course,
pathological mutations that affect the development
of testicles or spermatogenesis can not be inherited
because these individuals are sterile.

34. Every mitochondrion has circular chromosome. It was
described mutations of mitochondrion' different genes. There
were revealed genes mutations in the mitochondrial DNA at
patients with Leber's optic atrophy, mitochondrial myopathies,
benign tumors, progressive ophtalmoplegias.
Mithocongrions are transmitted with ovocyte`s cytoplasm.
Spermatozoon do not have mitochondrion because cytoplasm
is eliminated at spermatozoons maturing.
Characteristics:
 disease is inherited only from mother
 girls and boys are affected
 affected fathers do not transmit diseases neither daughters nor
sons.

35.  Identification/determination of sex chromatin
(X and Y chromatin)
 The study of chromosomes at metaphase of
mitosis to determine karyotype.

36.  In the laboratory diagnosis of hereditary
diseases biochemical methods are applied from
the beginning of XX century. Biochemical
parameters (the primary protein product of the
gene, the accumulation of abnormal
metabolites in cells and in the extracellular
fluid of patients) reflect the essence of the
disease more accurately than clinical
symptoms, not only in diagnosis, but also in
the genetic aspect. Biochemical methods aimed
at identifying the biochemical phenotype of the
organism.

37.  This is a large and diverse group of methods
ultimately intended for the detection of
variations in the structure of the investigated
DNA region up to decrypt the primary
nucleotide sequence. The basis of these
methods are "manipulation" of DNA and RNA.
The adoption of these methods, as well as other
methods of laboratory diagnosis ,requires
special training in the relevant laboratories.