Download Classification of genetic disorders

Genes
• Genes are the units of heredity. They
contain the hereditary information encoded
in their chemical structure for transmission
from generation to generation. They affect
development and function, both normal
and abnormal.
Genotypes
• Since genes are contained in the
chromosomes, genes also occur in pairs.
If the genes comprising a pair are alike
(AA), the individual is described as
homozygous for that gene.
• And if it is different (Aa) the individual is
described as heterozygous.
Mutation
• Genes are usually stable, but sometimes
normal genes may be converted into
abnormal ones - this change is called
mutation.
Mutation
is
a
regular
phenomenon in nature.
• The natural mutation rate is increased by
exposure to mutagens such as ultraviolet
rays, radiation or chemical carcinogens.
Genotype
• The term genotype refers to the total
genetic constitution of an individual But the
genotype is relatively stable throughout
the life of an individual. Thus there are two
aspects of the genetic material -one fixed
and the other plastic.
Phenotype
• The term phenotype refers to the outward
expression of the genetic constitution.
• Certain phenotype characteristics of an
individual may change from infancy to
adulthood such as height, weight,
muscularity, body shape, The fixed
characters are the genotype and the
plastic ones are the phenotype.
Chromosomal abnormalities
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Aneuploidy
Translocation
Deletion
Duplication
Inversion
Isochrqmosomes
Mosaicism
Classification of genetic
disorders
• These may be classified as
a. Chromosomal abnormalities
b. Unifactorial (single gene or Mendelian)
diseases
c. Multifactorial disorders
CHROMOSOMAL DISORDERS
• More than 300 numerical and structural
types of chromosome aberrations have
been described. A significant portion of
embryonic and foetal wastage is due to
chromosomal anomalies. The incidence of
chromosomal abnormalities is 5.6 per
1000 live births.
Klinefelter's Syndrome
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This is a common sex -chromosome
aneuploidy persons suffering from this
syndrome are abnormal males having
two or more X chromosomes in addition
to one Y-chromosome (XXY, XXXY).
They have a normal autosomal set of 22.
The main features of this syndrome are
that the affected persons are eunuchoid
males with non-functional testis.
XYY Syndrome
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The male with an extra Y chromosome has
attracted much attention because of his
reported tendency to anti-social, aggressive
and often criminal behavior. However, the
relationship is not yet clear. The principal
features of this syndrome appear to be
exceptional height (usually six feet and over)
and a serious personality disorder leading to
behavioural disturbances. The incidence of this
syndrome is about 1 in 1000 males at birth.
Turner's Syndrome
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Persons suffering from this syndrome are
apparent females with underdeveloped sex
glands. They have 45 chromosomes instead of
the normal complement of 46.
Clinically the patients are of short stature,
infertile and have primary amenorrhoea. They
often show other congenital defects such as
coarctation of the aorta, pulmonary stenosis,
renal malformations and mental retardation.
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"Super Females" : Females with 3 to 5 Xchromosomes (XXX, XXXX, XXXXX)
have beenfound. In general, the higher
the number of X-chromosomes, the
greater the degree of mental retardation
and congenital abnormalities, e.g.,
underdeveloped
external
genitalia,
uterus and vagina.
2. Relating to autosomes :
• There are many syndromes associated
with
abnormalities
of
autosomes.
mongolism is a public health problem in
some countries,
• Most cases of mongolism are caused by
an extra chromosome which occurs on the
21st pair.
mongolism
• The anomaly is therefore sometimes described
as "Trisomy 21". The syndrome is easily
recognised in the older child and adult by the
short stature and small round head, narrow,
tilted eye-slits, mal-formed ears, short broad
hands, lax limbs, mental retardation and quite a
few other abnormalities especially internal
congenital defects such as cardiac defects and
atresia of the alimentary tract. In communities of
European origin the incidence of mongolism at
birth is reported to be one in 900 births.
mongolism
• One observation which is important is that
the frequency of mongolism increases with
rising maternal age but is un-affected by
the age of the father. The risk for a woman
of 20 is estimated at about \ in 3,000 and
that for a woman of 45, 1 in 50.
"point" mutation
• Mendelian diseases are individually rare
since there is strong selection against
them and gene mutations are rare events.
Mutation usually occurs at random. If
mutation is confined to a single gene it is
called
"point"
mutation,
which
is
responsible for many human diseases and
defects.
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Blood groups
ABO SYSTEM
RHESUS SYSTEM
Erythroblastosis foetalis
Blood groups and disease
Sickle cell anemia
• Sickle cell anaemia is an autosomal
recessive disorder in which an abnormal
haemoglobin leads to chronic haemolytic
anaemia with a variety of severe clinical
consequences. The disorder is a classic
example of disease caused by a point
mutation in DNA. Individuals with one
gene of this disease are clinically healthy,
but their RBC look abnormal under the
microscope..
Thalassemias:
• The thalassemias are hereditary disorders
characterized by reduction in the synthesis of
globin chain (alpha or beta). Reduced globin
chain synthesis causes reduced haemoglobin
synthesis and eventually produces a hypo
chromic microcytic anaemia because of
defective haemoglobinization of red cells.
Thalassemias can be considered among hypoproliferate anemia's, the hemolytic anemia's, and
the anaemias related to abnormal haemoglobin,
since all of these factors may play a role.
• Haemophilia
• Cystic fibrosis
• Phenylketonuria
MULTIFACTORIAL DISORDERS
• Role of genetic predisposition in
common disorders:
• Cancer
• Coronary heart disease
• Diabetes
• Mental Disorders
Advances in molecular genetics
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DNA technology
Gene Therapy
The Human Genome Project
The Human Genome Diversity Project
PREVENTIVE AND SOCIAL MEASURES
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EUGENICS : Galton proposed the term
eugenics for the science which aims to
improve the genetic endowment of
human population. Eugenics has both
negative and positive aspects.
EuTHENICS :
Mere improvement of the genotype is of
no use unless the improved genotype is
given access to a suitable environment,
an environment which will enable the
genes to express themselves readily.
• (c ) GENETIC COUNSELLING
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(i) Prospective genetic counseling
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(ii) Retrospective genetic counseling
• OTHER—GENETIC PREVENTIVE
MEASURES
– Consanguinous marriages
– Late marriages
Specific protection
• Increasing attention is now being paid to the
protection of individuals and whole communities
against mutagens such as X-rays and other
ionizing radiations and also chemical mutagens.
Patients undergoing X-ray examination should
be protected against unnecessary exposure of
the gonads to radiation. X-ray examination of the
pregnant uterus to determine the presence of
twins or the lie of the foetus is to be strongly
deprecated. Rh haemolytic disease of the
newborn which is a genetically determined
immunological disorder is now preventable by
immunization by anti- D globulin.
Early diagnosis and treatment
• Detection of genetic carriers
• Prenatal diagnosis
Amniocentesis
• Amniocentesis is called for in the following
circumstances if
the parents are prepared to consider
abortion.
• 1. A mother aged 35 years or more
(because of high risk of Down's syndrome
with advanced maternal age).
• 2. Patients who have had a child with
Down's syndrome or other chromosomal
anomalies.
• 3. Parents who are known to have
chromosomal translocation.
• 4.
Parents who have had a child with a
metabolic defect -detectable by amniocentesis.
The most common are defects of the neural
tube, anencephaly and spina bifida which can be
detected by an elevation of alpha fetoprotein in
the amniotic fluid.
• 5. When determination of the sex is warranted,
given a family history of a sex-linked genetic
disease e.g., certain muscular dystrophies.
• c) Screening of newborn infants
• Recognizing preclinical cases
Rehabilitation
• Finally, rehabilitation. With many genetic
or partially genetic conditions causing
physical or mental disability, much can be
done for the patient and for his family in
helping him to lead a better and more
useful life.
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