GENETICS &

HEALTH

DR. HADEYA ANJUM (PT)

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Intro.
• A gene is the basic physical and functional unit of heredity.
Genes are made up of DNA... Every person has two copies of
each gene, one inherited from each parent.

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Intro.
• 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 & function, both normal and abnormal.

• We inherit about 50,000 genes from the father and 50,000 from the
mother.

• The genes occupy a specific position or locus on the chromosomes.

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• Genes are confined in the chromosomes, in the form of 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.

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• A gene is dominant when it manifests its effect both in the
heterozygous and the homozygous state.

• A gene is said to be recessive when it manifests its effect only in the

homozygous state.

• Genes whose combined action affects one particular character are

known as "multiple genes".

• In man three genes have been identified as being responsible for

muscular dystrophy one is a sex linked recessive gene, the second is an
autosomal recessive, and the third is an autosomal dominant gene.
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• Many instances are known in which the same character is controlled
by several genes - the color of our skin, height and weight, life span,
degree of resistance to disease, rate of heart beat, arterial blood
pressure and many other inherited traits.

• These genes may occupy separate positions in the chromosomes;

some may be widely distributed on several non-homologous
chromosomes.

• The extent to which a genetically determined condition is expressed

in an individual is called penetrance. Lack of penetrance is one reason
for skipped generations and unexpected pedigree patterns.

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• 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;
i. ultraviolet rays
ii. Radiation
iii. chemical carcinogens

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 Classification of Genetic
Disorders
These may be classified as :

a. Chromosomal abnormalities
b. Unifactorial (single gene or Mendelian) diseases
c. Multifactorial disorders

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 Chromosomal Disorders
• More than 300 numerical and structural types of chromosome
abnormalities have been described.
• A significant portion of embryonic and fetal wastage is due to
chromosomal anomalies.
• The incidence of chromosomal abnormalities is 5.6/1000 live births.
Of these, 2/1000 live births represent sex aneuploidies, 1.7/1000 live
births autosomal aneuploidies, and 1.9/1000 live births chromosomal
translocations. These disorders are not inherited.
1. Related to sex chromosome
2. Related to autosome
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 Mendelian Diseases
• Mendelian diseases are inherited according to the Mendelian Laws
i.e. the manner by which genes and traits are passed from parents to
their children.
• These are the dominant, recessive and sex-linked diseases

BLOOD GROUPS
Early genetic studies centered round blood groups in man. Blood
groups are determined by genes. At present 14 blood group systems
have been discovered in man; the well-known ones are the ABO and Rh
blood groups.
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Erythroblastosis Fetalis
• Hemolytic anemia in the fetus

• If the fetus is Rh-positive and the mother Rh-negative, certain

consequences are likely.

• Some of the fetal red cells cross the placenta and enter the maternal
circulation where they act as foreign antigen and the production of Rh
antibodies.

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Blood Groups & Disease
• During the past 10 years researchers have been trying to find out the
association of certain diseases with particular blood groups. However,
only two disease conditions have shown such association with the
ABO groups.

• Duodenal ulcer and gastric ulcer are common in 'O' group and
stomach cancer in 'N group individuals.

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Sickle Cell Anemia
• Sickle cell anemia is an autosomal recessive disorder in which an abnormal
hemoglobin leads to chronic hemolytic anemia 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 RBCs
look abnormal under the microscope.

• Persons with 2 genes (homozygous) of this disease suffer from acute anemia and
in most cases die before puberty.
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Thalassaemias
• The thalassemia's are hereditary disorders characterized by reduction
in the synthesis of globin chain (alpha or beta).

• 13.educed globin chain synthesis causes reduced hemoglobin

synthesis and eventually produces a hypochromic microcytic anemia
because of defective hemoglobinization of red cells.

• Thalassaemias can be considered among hypo-proliferative anemias,

the hemolytic anemias, and the anemias related to abnormal
hemoglobin, since all of these factors may play a role.
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Hemophilia
• Hemophilia is a hereditary bleeding disorder affecting 15-20 of every
100,000 males born.

• Prevalence, which depends on survival, varies according to available

medical care.

• There are an estimated 420,000 people with hemophilia worldwide.

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Cystic Fibrosis
• Cystic fibrosis is a genetic disease occurring worldwide, which affects
the respiratory and gastrointestinal tracts and the sweat glands.

• Incidence ranges from 2.5 to 5/10,000 live births in most European

populations. The condition is less common in blacks, and rare in
Orientals.

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Phenyl-ketonuria PKU
• Phenylketonuria is an autosomal recessive disorder resulting in a
deficiency of the liver enzyme phenylalanine hydroxylase which
converts phenylalanine to tyrosine.

• The frequency of the disease is about 1 in 10,000 births.

Phenylalanine accumulates in the blood and tissues and has a toxic
effect on the brain leading to mental retardation.

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Multi Factorial Disorders
• The frequency of multifactorial disorders is high compared with that
of Mendelian and chromosomal disorders.

• There are indications that most of the common disorders of adult life
such as essential hypertension, schizophrenia, mental retardation,
duodenal ulcer, ischemic heart disease of early onset, diabetes,
congenital heart malformations are conditions with a multifactorial
etiology.

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Prevention Of Genetic Disorders
• Health promotional measures:
a) eugenics
b) euthenics
c) genetic counselling
d) other genetic preventive measures (cousin marriage, late marriage)

• Specific protection

• Early diagnosis and treatment

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Eugenics
• The term eugenics aims to improve the genetic endowment of human
population. Eugenics has both negative and positive aspects.

i. Negative: To reduce the frequency of hereditary disease and

disability (by killing the weak and defective) in the community to as
low as possible.
ii. Positive: To improve the genetic composition of the population by
encouraging the carriers of desirable genotypes to assume the
burden of parenthood.

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Euthenics
• Just 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.
• Man has been adapting environment to his genes more than adapting his
genes to the environment.
• Studies with mentally retarded (mild) children indicated that exposure to
environmental stimulation improved their IQ.
• Thus the solution of improving the human race does not lie in contrasting
heredity and environment, but rather in the mutual interaction of heredity
and environmental factors.
• This environmental manipulation is called euthenics and has considerable
broader prospects for success. 22
Genetic Counselling
• The most immediate and practical service that genetics can render in
medicine and surgery is genetic counselling.
• Genetic counselling may be;

i. prospective
ii. retrospective.

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Prospective Genetic Counselling:
• This allows for the true prevention of disease.
• Identifying heterozygous individuals for any particular defect by
screening procedures and explaining to them the risk of their having
affected children if they marry another heterozygote for the same gene.
• In other words, if heterozygous marriage can be prevented or reduced,
the predictions of giving birth to affected children will diminish.
• The application in this field, for example, are sickle cell anemia and
thalassemia.
• It is possible that this kind of prevention may find wider application to
cover a number of other recessive defects.

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Retrospective Genetic Counselling:

• Most genetic counselling is at present retrospective, i.e., the

hereditary disorder has already occurred within the family.
• Genetic advice is chiefly sought in connection with congenital
abnormalities, mental retardation, psychiatric illness and inborn
errors of metabolism and only a few sought premarital advice.
• WHO recommends the establishment of genetic counselling centers
in sufficient numbers in regions where infectious disease and
nutritional disorders have been brought under control and in areas
where genetic disorders have always constituted a serious public
health problem (e.g., sickle cell anemia and thalassemia).

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The methods which could be suggested under retrospective genetic
counselling are :

(i) Contraception
(ii) Pregnancy termination and
(iii) Sterilization depending upon the attitudes and cultural
environment of the couples involved.

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Other Genetic Preventive
Measures
i) Consanguineous Marriages:
When blood relatives marry each other there is an increased risk in the
offspring of traits controlled by recessive genes, and those determined
by polygenes.

Examples are albinism, alkaptonuria, phenylketonuria and several

others. An increased risk of premature death is also noted in such
offspring.

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alkaptonuria
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(ii) Late marriages:

• The pendulum is swinging in favor of early marriages.

• The discovery of "Trisomy 21" in Mongols coupled with the

knowledge that mongolism is more frequent in children born of
elderly mothers, lends support to the view that early marriage of
females is better than late marriage from the point of view of
preventing mongolism.

• Its incidence in a mother at age 20 is only 1 : 3000; by the age 40, it is

1:40.
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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 fetus is to be strongly .. deprecated.
• Rh hemolytic disease of the newborn which is a genetically
determined immunological disorder is now preventable by
immunization by anti-D globulin.
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Early Diagnosis & Treatment
i. Detection of genetic careers
ii. Pre-natal diagnosis
iii. Amniocentesis
iv. Screening of newborn infants
v. Recognizing pre-clinical cases

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Amniocentesis
• Examination of a sample of amniotic fluid makes possible the prenatal
diagnosis of chromosomal anomalies and certain metabolic defects.

• The procedure can be used as early as 14th week of pregnancy when

abortion of the affected fetus is still feasible.

• The diagnosis of chromosomal anomalies is made by culture and

Karyotyping of fetal cells from the amniotic fluid, and of metabolic
defects by biochemical analysis of the fluid.

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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. 35
• For the detection of neural tube defects there is now the possibility of
widespread screening by the determination of alpha-fetoprotein
levels in the maternal serum.

• If the test is positive it can be confirmed by amniocentesis.

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 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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