BIOLOGY

PROJECT

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 CERTIFICATE

This is to certify that Hridya Ullas, student of class XII of Sudarsanam Central
School has successfully completed the project in biology on the topic ‘Genetic
Disorder’ for the year 2022-2023 under the guidance of Mrs. Heera Raj.

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 Acknowledgement

I thank God Almighty for this kindest blessing showered upon me to fulfil this project
successfully.

I express my sincere gratitude your principal Mrs Bincy Susan Titus for giving me the
opportunity undertake this project.

I am greatly indebted to my respected teacher Mrs Heera Raj Department of Biology

under whose guidance this work had been carried out.

I am thanking to all the staff for their selfless and dedicated service which enabled me
in completing this project.

I would also like to thank my parents and friends who helped me a lot in finishing this
project within the limited time through their valuable suggestions and support.

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 CONTENTS

1. INTRODUCTION
2. HISTORY
3. THEORY
❖ Pedigree Analysis
❖ Mendelian Disorder
• Colour Blindness
• Haemophilia
• Sickle Cell Anaemia
• Phenylketonuria
• Cystic Fibrosis
• Thalassemia
❖ Chromosomal Disorder
• Down’s Syndrome
• Klinefelter’s Syndrome
• Turner’s Syndrome
4. CONCLUSION
5. BIBLIOGRAPHY

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 Introduction
Genes are the building block of heredity. They are pass from parents to child.
they hold DNA, the instructions from making proteins. Proteins do most of the work in
cells. They molecules from one place to another, build structures, break down toxins
and do many other maintenance jobs.

Sometimes there is a mutation, a change in a gene or genes. The mutation

changes the genes instructions for making a protein, so the protein does not work
properly or is missing entirely. this can cause a medical condition called a genetic
disorder.

You can inherit a gene mutation from one or both parents. Mutation can also
happen during your lifetime.

There are three types of genetic disorders:

* Single gene disorders, where a mutation effects one gene. Sickle cell anaemia is an
example.

* Chromosomal disorder, where chromosomes (or parts of chromosomes) are missing

or changed. Chromosomes are the structures that hold our genes. Down syndrome is a
chromosomal disorder.

* Complex disorders, where there are mutations in two or more genes. Often your
lifestyle and environment also play a role. colon cancer is an example.

Genetic test on blood and other tissue can identify genetic disorders.

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 History
First, there was Gregor Mendel, a monk who studied inherited
characteristics. This was followed by Francis Crick and James Watson, who unravelled
the DNA molecule. This has led us to understanding the human genome sequence.

Gregor Mendel. 1866 published the result of his investigations of the

Inheritance of “factors “in pea plans.

Rosalind Franklin 1950s, Maurice Wilkins 1916 Francis HC Crick 1916 and
James D Watson 1928 discover chemical structure of DNA, starting a new branch of
science- molecular biology.

Watson and Crick made a model of the DNA molecule and proved that genes
determine heredity.

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 Theory

PEDIGREE ANALYSIS

A pedigree chart is a set diagram that shows the occurrence and appearance or
phenotypes of a particular gene or organism and its ancestors from one generation to
the next, most humans, show dogs and race horse.

Pedigree analysis is also useful when studying any population when progeny
data from several generations is limited. Pedigree analysis is also useful when studying
species with a long generation time. A series of symbols are used to represent different
aspects of a pedigree.

Once phenotypic data is collected from several generations and the Pedigree
is drawn, careful analysis will allow you to determine whether the trait is dominant or
recessive. Here are some rules to follow,

➢ For those traits exhibiting dominant gene action:

• Affected individuals have at least one affected parent.

• The phenotype generally appears every generation
• Two unaffected parents only have unaffected offspring.

➢ For those traits exhibiting recessive gene action:

• Unaffected parents can have affected offspring

• Affected progeny are both male and female

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9
 MENDELIAN DISORDER
Mendelian disorder is a category of Genetic Disorder. They are mainly
determined by alteration or mutation in the single gene. These disorders are transmitted
to the offspring on the same lines as in the principle of inheritance. The pattern of such
inheritance of mendelian disorders can be traced in a family by pedigree analysis. Most
common and prevalent mendelian disorders are Haemophilia, Cystic Fibrosis, Sickle-
Cell anaemia, and Thalassemia. Such Mendelian Disorders may be dominant or
recessive. Similarly, the trait may also be linked to the sex chromosome as in case of
Haemophilia.

It is evident that this X-linked recessive trait shows transmission from carrier
female to male progeny

Examples of Mendelian Disorders in Humans:

1. Colour blindness
Colour blindness is also known as colour vision Deficiency (CVD), is a
syndrome which was discovered in 1798 by John Dalton. It is defined as the trouble in
seeing or identifying various colours like blue, green, and red. There are also some rare
cases in which a person with this colour blindness will also find difficulties in
differentiating the spectrum of shades of colours. This syndrome is also called Colour
Vision Problem.

➢ Types of Colour Blindness

It is majorly of two types:

• Monochromacy
• Dichromacy

• Monochromacy

This type of syndrome occurs when two or three cone pigments (these
are the colouring agents) – red, blue, and green are absent or damaged. In this type of

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colour blindness both the colour and lightness vision are reduced to one dimension. This
results in total colour blindness and an individual is only able to see in black and white.

• Dichromacy

This syndrome occurs when only one of the three cone pigments is absent or
damage in the human cells. In this type, only the colour vision is reduced to two
dimensions. This result in partial colour blindness.

➢ Causes of colour blindness.

The healthy retina of the human eye contains two light-sensitive cells, which are
the rod cells and the cone cells. The rod cells are responsible for low light vision,
whereas the cone cells are responsible for normal, bright, light and coloured vision.

Colour blindness is affected when any of these two light sensitive cells fail to
perform their functions.

There are several other factors which can cause colour vision problems in an individual.
The factors may include:

• Damage cost to the brain or eye or the nephews.

• Genetic disorders and cell mutation.
• Side effects of drug addiction.
• Use of narcotics

➢ Symptoms Of Colour Blindness

The symptoms of colour blindness include the following:

• Rapid and continuous eye movement.

• Sensitivity towards bright light.
• Trouble in saying different colours. And the brightness of any
respective colour
• Your problem is differentiation between various shades of the same
colour

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 ➢ Complications Of Colour Blindness
People with a severe form of colour blindness called achromatopsia cannot see any
colours — they only see black, white, and shades of grey. They may also have other
vision problems such as sensitivity to light and glare, uncontrollable eye movements
(nystagmus), low visual acuity (not being able to see things sharply), and farsightedness.
Achromatopsia is rare — it affects approximately 1 in 30,000 people worldwide.

➢ Diagnosis of Colour Blindness

There are several tests available for diagnosis and to measure the extent of
colour vision deficiency in a patient. Doctors usually prefer the play touch test and the
screening test to do the diagnosis colour blindness in a patient.

➢ Treatment A Colour Blindness

Currently, there is no specific treatment for this syndrome but various
photographic frames or filters and eyeglasses with contact lenses are used at a certain
extent to restore and improve the dimension between some colours. A proper balance
diet also needs to be followed to improve the symptoms of colour blindness.

Red and green colour blindness is the most common type of inherited
colour blindness.

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2. Haemophilia
Haemophilia is a disorder in which a person's blood does not clot normally
which can lead to a spontaneous or excessive bleeding, according to the centres for
Disease Control and prevention. Blood contains protein called clotting factors which
can help to stop bleeding the CDC notes. People with haemophilia have lower than
normal levels of certain clotting factors, which can make bleeding more likely to occur.
Haemophilia is a genetic disorder manifest later in life - usually in middle age or older
people or women who have just given birth or are in the final months of pregnancy.
Haemophilia is rare and it mostly effects males it can be mild, moderate or severe
depending how much clotting factor is in the blood.

➢ Types of Haemophilia
▪ Haemophilia A

It is the most common type of haemophilia caused by an insufficient

amount of clotting factor 8. It is an inherited disorder, about one third of cases are caused
by a spontaneous gene mutation or according to the national haemophilia Foundation
(NHF). Haemophilia a is much more common in males. It rarely occurs in females.
People with haemophilia a typically bleed for long periods of time that other people.
Types of breathing cap occur: internal bleeding and external bleeding.

▪ Haemophilia B

Haemophilia B results from insufficient amount of clotting factor 9.

like haemophilia a it is a genetic disorder with about one third of cases caused by
spontaneous mutation NHF people with Haemophilia B delete for a period of time than
people who do not have the disorder bleeding can occur internally enjoying and muscles
or externally.

▪ Haemophilia C

Haemophilia C is caused by a lack of factor II per NORD. unlike

type a and b spontaneous bleeding or bleeding in the joints does not occur unless there
is underlying joint diseases are more likely scenario for a person with Haemophilia C
is extended bleeding after surgery then then procedures or trauma men and women are
equally affected by Haemophilia C.

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 ➢ Causes of Haemophilia
In Haemophilia, A and B. The gene for haemophilia is carried on
the X-chromosome. Females inherit two X chromosomes; one from their mother and
one from their fathers. Males inherit an X chromosome from their mother and Y
chromosome from their father. If a son inherits an X chromosome carrying haemophilia
from his mother, he will have haemophilia. Fathers can’t pass haemophilia to their sons.

Even if females inherit the haemophilia gene from their mother, they are likely
to inherit a healthy X chromosome from their father, so they are unlikely to have
haemophilia. A daughter who inherits an X chromosome that has a mutation in the gene
for haemophilia is carrier and she can pass the gene on to her children. Haemophilia
rarely occurs in daughters. About 30% of people with haemophilia have no history of
the disorder in their family, but it manifests when an unexpected change occurs in one
of genes associated with haemophilia

In Haemophilia C, a deficiency in clotting factor II is caused by mutation to the

F11 gene. It is usually inherited, but in rare instances, new or spontaneous mutations
may occur in an individual causing the disorder.

➢ Symptoms of Haemophilia
The symptoms of haemophilia include:

• Bleeding into the joints which can cause swelling and pain or tightness in the
joints
• Bleeding into the skin or into muscle and soft tissue causing and accumulation
of blood
• Bleeding of the mouth and gums that is difficult to stop after losing a tooth
• Bleeding after circumcision
• Bleeding after having shots or vaccines
• Bleeding in the head of an infant after the baby is delivered
• Blood in the urine of stool

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 ➢ Complications of Haemophilia
Complications of haemophilia can include:

• Deep internal bleeding. Bleeding that occurs in deep muscle can cause the limbs
to swell. The swelling can press on nerves and lead to numbness or pain.
Depending on where the bleeding occurs, it could be life-threatening.
• Bleeding into the throat or neck. This can affect a person's ability to breathe.
• Damage to joints. Internal bleeding can put pressure on the joints, causing severe
pain. Left untreated, frequent internal bleeding can cause arthritis or destruction
of the joint.
• Infection. If the clotting factors used to treat haemophilia come from human
blood, there's an increased risk of viral infections such as hepatitis C. Because of
donor screening techniques, the risk is low.
• Adverse reaction to clotting factor treatment. In some people with severe
haemophilia, the immune system has a negative reaction to the clotting factors
used to treat bleeding. When this happens, the immune system develops proteins
that keep the clotting factors from working, making treatment less effective.

➢ Diagnosis of Haemophilia.
It’s common for people who have or have had family members with
haemophilia to get there. Baby boys tested for the condition shortly after they’re born,
note the CDC. Ideally, testing is planned before the baby’s birth so that a blood sample
can be drawn from the umbilical cord. Umbilical cord blood testing is better at
discovering low levels of factor 8 than at finding low levels of factor 9, because factor
9 levels are not at a normal level until a baby is at least 6 months old. Two types of
testing are used for diagnosis: screening tests and clotting factor test which are also
called factor assays.

➢ Treatment for Haemophilia.

The best way to manage haemophilia is often through comprehensive
haemophilia treatment Centre (HTC), notes the CDC. These centres include all the
different types of providers - specialists such as haematologist, as well as nurses,
counsellors and physical therapists that a person with haemophilia needs. The primary

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treatment for haemophilia is replaced the missing clotting factor so the blood can clot
properly, according to the CDC. The two main replacement therapies are plasma
derived factor concentrates and recombinant factor concentrates. These are both
administrated through injections.

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3.Sickle Cell Anaemia
Sickle cell anaemia is the most common form of sickle cell disease (SCD).
SCD is a serious disorder in which the body makes sickle shaped red blood cells. Sickle
shaped means that the red blood cells are shaped like a crescent Normal blood cells are
disk- shaped and look like doughnuts without holes in the centre. They move easily
through your blood vessels. Red blood cells contain an iron rich protein called
haemoglobin. This protein carries oxygen from the lungs to the rest of the body. Sickle
cells contain abnormal haemoglobin called sickle haemoglobin or haemoglobin S.
Sickle haemoglobin causes the cells to develop a sickle or crescent shape.

Sickle cells are stiff. And sticky. They tend to block blood flow in the
blood vessels of limp and organs. Block blood flow can cause pain and organ damage.
It can also raise the. Risk for infection.

➢ Sickle-Cell Mutation
Normal B-Globin

DNA TGA CGA CTC CTC

MRNA ACU CCU GAG GAG

Amino acid -thr pro glu glu

Mutant B-Globin

DNA TGA CGA CAC CTC

MRNA ACU CCU GUG CTC

Amino acid thr pro val glu.

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 ➢ Types Of Sickle Cell Anaemia
Haemoglobin is the protein in red blood cells that carries oxygen. It
normally has two alpha chains and two beta chains. The four main types of sickle
cell anaemia are caused by different mutations in these genes.

▪ Haemoglobin SS disease

Haemoglobin SS disease is the most common type of sickle cell disease. It

occurs when you inherit copies of the haemoglobin S gene from both parents. This
forms haemoglobin known as Hb SS. As the most severe form of SCD, individuals with
this form also experience the worst symptoms at a higher rate.

▪ Haemoglobin SC disease

Haemoglobin SC disease is the second most common type of sickle cell

disease. It occurs when you inherit the Hb C gene from one parent and the Hb S gene
from the other. Individuals with Hb SC have similar symptoms to individuals with Hb
SS. However, the anaemia is less severe.

▪ Haemoglobin SB+ (beta) thalassemia

Haemoglobin SB+ (beta) thalassemia affects beta globin gene production. The
size of the red blood cell is reduced because less beta protein is made. If inherited with
the Hb S gene, you will have haemoglobin S beta thalassemia. Symptoms are not as
severe.

▪ Haemoglobin SB 0 (Beta-zero) thalassemia

Sickle beta-zero thalassemia is the fourth type of sickle cell disease. It also
involves the beta globin gene. It has similar symptoms to Hb SS anaemia. However,
sometimes the symptoms of beta zero thalassemia are more severe. It is associated with
a poorer prognosis.

▪ Haemoglobin SD, haemoglobin SE, and haemoglobin SO

These types of sickle cell disease are rarer and usually don’t have severe
symptoms.

▪ Sickle cell trait

People who only inherit a mutated gene (haemoglobin S) from one parent
are said to have sickle cell trait. They may have no symptoms or reduced symptoms.
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 ➢ Cause of Sickle cell Anaemia
Sickle cell anaemia is an inherited disease. People who have the disease
inherit two genes for sickle haemoglobin-one from each parent.

Sickle haemoglobin causes red blood cells to develop a sickle or crescent,

shape. Sickle cells are stiff and sticky. They tend to block blood flow in the blood
vessels of the limbs and organs. Blocked blood flow can cause pain and organ damage.
It can also raise the risk for infection.

➢ Symptoms Of Sickle Cell Anaemia.

The symptoms of sickle cell anaemia vary. Some people have mild
symptoms. Others have very severe symptoms and often are hospitalized for treatment.
Sickle cell anaemia is present at birth, but many infants don’t show any signs until after
four months of age. The most common symptoms are linked to anaemia and pain.

➢ Complications Of Sickle Cell Anaemia

Sickle Cell crisis can affect many parts of the body and cause many
complications like

i. Hand Foot Syndrome

Sickle cells can block the small blood vessels in the hands and feet
in children (usually those younger than 4 years of age). This condition is called
hand-foot syndrome. It can lead to pain, swelling, and fever. Swelling often
occurs on the back of the hands and feet and moves into the fingers and toes.
One or both hands and/or feet might be affected at the same time.

ii. Splenic Crisis

The spleen is an organ in the abdomen. Normally, it filters out
abnormal red blood cells and helps fight infections. Sometimes the spleen may
trap red blood cells that should be in the bloodstream. This causes the spleen to
grow large and leads to anaemia. If the spleen traps too many red blood cells,
you may need blood transfusions until your body can make more cells and
recover.

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iii. Infections
Both children and adults who have sickle cell anaemia may get
infections easily and have a hard time fighting them. This is because sickle cell
anaemia can damage the spleen, an organ that helps fight infections.

Infants and young children who have damaged spleens are more likely
to get serious infections that can kill them within hours or days. Bloodstream
infections are the most common cause of death in young children who have
sickle cell anaemia. Medicines and vaccines can help prevent severe illness and
death. For example, vaccines are available for infections such as meningitis,
influenza, and hepatitis.

Getting treatment right away for high fevers (which can be a sign of a
severe infection) also helps prevent death in infants and children who have sickle
cell anaemia. It's also important to get treatment right away for a cough, problems
breathing, bone pain, and headaches.

iv. Acute Chest Syndrome

Acute chest syndrome is a life-threatening condition linked to sickle
cell anaemia. This syndrome is similar to pneumonia. An infection or sickle cells
trapped in the lungs can cause acute chest syndrome. People who have this
condition often have chest pain, shortness of breath, and fever. They also often
have low oxygen levels and abnormal chest X ray results.

v. Pulmonary Hypertension
Damage to the small blood vessels in the lungs makes it hard for the
heart to pump blood through the lungs. This causes blood pressure in the lungs
to rise. Increased blood pressure in the lungs is called pulmonary hypertension
(PH). Shortness of breath and fatigue are the main symptoms of PH.

vi. Delete Growth Puberty In Children

Children who have sickle cell anaemia often grow more slowly than other
children. They may reach puberty later. A shortage of red blood cells causes the
slow growth rate. Adults who have sickle cell anaemia often are slender or
smaller in size than other adults.

vii. Stroke
Two forms of stroke can occur in people who have sickle cell anomia.
One form occurs if a blood vessel in the brain is damaged and blocked. This type
of stroke occurs more often in children than adults. The other form of stroke
occurs if a blood vessel in the brain bursts. Either type of stroke can cause
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 learning problems and lasting brain damage, long-term disability, paralysis (an
inability to move), or death.

viii. Eye Problems

Sickle cells also can affect the small blood vessels that deliver oxygen-
rich blood to the eyes. Sickle cells can block these vessels or cause them to break
open and bleed. This can damage the retinas—thin layers of tissue at the back of
the eyes. The retinas take the images you see and send them to your brain. This
damage can cause serious problems, including blindness

ix. Priapism
Males who have sickle cell anaemia may have painful, unwanted
erections. This condition is called priapism. It happens because the sickle cells
block blood flow out of an erect penis. Over time, priapism can damage the penis
and lead to impotence.

x. Gall Stones
When red blood cells die, they release their haemoglobin. The body
breaks down this protein into a compound called bilirubin. Too much bilirubin
in the body can cause stones to form in the gallbladder, called gallstones.
Gallstones may cause steady pain that lasts for 30 minutes or more in the upper
right side of the belly, under the right shoulder, or between the shoulder blades.
The pain may happen after eating fatty meals.

People who have gallstones may have nausea (feeling sick to the
stomach), vomiting, fever, sweating, chills, clay-coloured stools, or jaundice.

xi. Ulcers On The Legs

Sickle cell ulcers (sores) usually begin as small, raised, crusted sores on
the lower third of the leg. Leg sores may occur more often in males than in
females. These sores usually develop in people who are aged 10 years or older.
The cause of sickle cell ulcers isn't clear. The number of ulcers can vary from
one to many. Some heal quickly, but others persist for years or come back after
healing.

xii. Multiple Organ Failure

Multiple organ failure is rare, but serious. It happens if you have a sickle
cell crisis that causes two out of three major organs (lungs, liver, or kidneys) to
fail. Often, multiple organ failure occurs during an unusually severe pain crisis.

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 Symptoms of this complication are fever, rapid heartbeat, problems breathing,
and changes in mental status (such as sudden tiredness or confusion).

➢ Diagnosis of Sickle Cell Anaemia

A simple blood test done at any time during a person's lifespan can detect
whether he or she has sickle haemoglobin. However early diagnosis is very important.
Health providers from a new-born screening follow-up program may contact you
directly to make sure you’re aware of the test results. If the test shows some sickle
haemoglobin, a second blood test should be done as soon as possible and within the first
few months of life. The primary care doctors may send you to a haematologist for a
second blood test. This doctor also can provide treatment for sickle cell disease.

Doctors also can diagnose sickle cell anaemia before birth. This is done
using a sample of amniotic fluid or tissue taken from the placenta. Testing before birth
can be done easily as10 weeks into the pregnancy. This testing looks for sickle
haemoglobin gene, rather than the abnormal haemoglobin that the gene makes.

➢ Treatment For Sickle Cell Anaemia

Sickle cell anaemia has no widely available cure. However, treatments can
help relieve symptoms and treat complications. The goals of treating sickle cell anaemia
are to relive pain; prevent infections; organ damage and strokes and control
complications.

Blood and Marrow Stem Cell Transplant

A blood and marrow stem cell transplant can work well for treating sickle cell
anaemia. This treatment may even offer a cure for a small number of people. The stem
cells used for a transplant must come from a closely matched donor. The donor usually
is a close family member who doesn't have sickle cell anaemia. This limits the number
of people who may have a donor.

The transplant process is risky and can lead to serious side effects or even death.
However, new transplant approaches may improve treatment for people who have sickle
cell anaemia and involve less risk. Blood and marrow stem cell transplants usually are

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used for young patients who have severe sickle cell anaemia. However, the decision to
give this treatment is made on a case-by-case basis.

Researchers continue to look for sources of bone marrow stem cells—for

example, blood from babies' umbilical cords. They also continue to look for ways to
reduce the risks of this procedure.

Gene Therapy

Gene therapy is being studied as a possible treatment for sickle cell anaemia.
Researchers want to know whether a normal gene can be put into the bone marrow stem
cells of a person who has sickle cell anaemia. This would cause the body to make normal
red blood cells.

New Medicines

Researchers are studying several medicines for sickle cell anaemia. They
include:

• Decitabine: Like hydroxyurea, this medicine prompts the body to make Fetal
haemoglobin. Fetal haemoglobin helps prevent red blood cells from sickling and
improves anaemia. Decitabine might be used instead of hydroxyurea or added to
hydroxyurea.

• Adenosine A2a receptor agonists: These medicines may reduce pain-related

complications in people who have sickle cell anaemia.

• 5-HMF: This natural compound binds to red blood cells and increases their
oxygen. This helps prevent the red blood cells from sickling.

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4.Phenylketonuria (PKU)
Phenylketonuria (PKU) is a rare genetic condition that causes an amino acid
called phenylalanine to build up in the body. Amino acids are the building blocks of
protein. Phenylalanine is found in all proteins and some artificial sweeteners.

Phenylalanine hydroxylase is an enzyme your body uses to convert

phenylalanine into tyrosine, which your body needs to create neurotransmitters such as
epinephrine, norepinephrine, and dopamine. PKU is caused by a defect in the gene that
helps create phenylalanine hydroxylase. When this enzyme is missing, your body can’t
break down phenylalanine. This causes a build-up of phenylalanine in your body.

➢ Types of Phenylketonuria
There are four types of PKU:

• Hyperphenylalaninemia: the lowest level above normal

• Mild PKU: blood levels are mildly elevated
• Moderate or variant: levels are not low but not high
• Classic PKU: blood levels of phenylalanine are high

➢ Causes Of Phenylketonuria
PKU is an inherited condition caused by a defect in the PAH gene. The PAH
gene helps create phenylalanine hydroxylase; the enzyme responsible for breaking
down phenylalanine. A dangerous build-up of phenylalanine can occur when someone
eats high-protein foods, such as eggs and meat.

Both parents must pass on a defective version of the PAH gene for their child
to inherit the disorder. If just one parent passes on an altered gene, the child won’t have
any symptoms, but they’ll be a carrier of the gene.

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 ➢ Symptoms Of Phenylketonuria
PKU symptoms can range from mild to severe. The most severe form of this
disorder is known as classic PKU. An infant with classic PKU may appear normal for
the first few months of their life. If the baby isn’t treated for PKU during this time,
they’ll start to develop the following symptoms:

• seizures
• tremors, or trembling and shaking
• stunted growth
• hyperactivity
• skin conditions such as eczema
• a musty odour of their breath, skin, or urine

➢ Complications Of Phenylketonuria
Untreated PKU can lead to complications in infants, children and adults with
the disorder. When women with PKU have high blood phenylalanine levels during
pregnancy, it can harm their unborn baby.

Untreated PKU can lead to:

• Irreversible brain damage and marked intellectual disability beginning within the
first few months of life
• Neurological problems such as seizures and tremors
• Behavioural, emotional and social problems in older children and adults
• Major health and developmental problems

➢ Diagnosis of Phenylketonuria
Since the 1960s, hospitals in the United States have routinely screened new-
borns for PKU by taking a blood sample. A doctor uses a needle or lancet to take a few
drops of blood from your baby’s heel to test for PKU and other genetic disorders.

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 The screening test is performed when the baby is one to two days old and still
in the hospital. If you don’t deliver your baby in a hospital, you’ll need to schedule the
screening test with your doctor.

Additional tests may be performed to confirm the initial results. These tests
search for the presence of the PAH gene mutation that causes PKU. These tests are often
done within six weeks after birth.

If a child or adult shows symptoms of PKU, such as developmental delays, the

doctor will order a blood test to confirm the diagnosis. This test involves taking a sample
of blood and analysing it for the presence of the enzyme needed to break down
phenylalanine.

➢ Treatment Of Phenylketonuria
Treatment for PKU is lifelong. It may include a special diet or medication.
Treatment could include:

• Eating a special diet low in phenylalanine but full of nutrients.

• Taking vitamins, minerals and supplements.

Adding a supplemental medication called sapropterin dihydrochloride to

break down phenylalanine in your body. A medication called Pegvaliase allows people
with PKU to eat an unrestricted diet without any supplements or Kuvan. This
medication replaces the enzyme that helps to break down phenylalanine, which doesn’t
work properly in PKU.

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5.Cystic Fibrosis

CF is a genetic disease that mainly affects the lungs and digestive system. It
can also cause complications, such as liver disease and diabetes.

People with CF have a genetic mutation in a gene called the cystic fibrosis
transmembrane conductance regulator (CFTR). This gene controls the CFTR protein.

The protein is present in every organ that creates mucus. It is also present
in other organs and tissues, including those in the:

• Lungs
• pancreas
• intestines
• liver
• heart
• immune system
• sweat glands

The genetic mutation means that the CFTR protein does not function as it
would in a healthy body. This malfunctioning causes the body to produce mucus that is
thicker and stickier than usual. It can block the airways, causing breathing difficulties
and severe lung infections.

The genetic mutation may also interfere with pancreatic function by

preventing enzymes from breaking down food effectively. This can cause digestive
problems that may lead to limited growth and malnutrition.

CF is a chronic condition with potentially life-threatening complications.

However, treatments can improve the quality and duration of life.

➢ Types Of Cystic Fibrosis

CFTR mutations are generally grouped into different classes based on
how they affect the CFTR protein. In general, mutations that result in a more substantial
defect in the protein — for example, mutations that prevent any protein from being
made at all — are associated with more severe disease.

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 Because different mutations cause different changes to the protein, they
also may affect what treatment options are available for a given individual. For instance,
CFTR modulators are a type of medication that can address defects in the CFTR protein
caused by specific types of mutations.

No CFTR mRNA or protein

When a protein is going to be made in a cell, an enzyme called RNA

polymerase binds to a region in the DNA called a promoter, which is located right at
the start of the gene coding sequence. This enzyme then “reads” the gene to make an
intermediate molecule called messenger RNA, or mRNA. Next, this mRNA is sent to
the cell’s protein-making machinery, which uses it as a template to ultimately produce
a protein.

If the promoter for CFTR contains a mutation, it can lead to the RNA
polymerase not being able to bind to the DNA, and therefore not being able to copy the
message into mRNA. The end result is no CFTR protein being produced at all.

Examples of mutations that lead to no CFTR mRNA include the Dele2,3(21 kb)
and 1717-1G→A. They have been grouped in class IA, one of the more severe forms
of the disease.

Nonsense mutations

When a cell’s protein-making machinery “reads” a gene to make a protein,

there is a specific sequence in the genetic code, called a stop codon, that signals when
the machinery has reached the end of the gene — sort of like how a period denotes the
end of a sentence.

A nonsense mutation is a type of mutation that results in a stop codon in the

middle of the gene. This causes the production of a shortened version of the CFTR
protein, which is then degraded by the cell. Gly542X and Trp1282X are examples of
CF-causing nonsense mutations and are in class IB.

30
Trafficking defects

After the CFTR protein gets made, it needs to be shuttled to the cell’s
membrane so it can perform its normal function. Some mutations cause the CFTR
protein to misfold, which can prevent it from being transported appropriately.

Examples of this type of mutation (class II) include F508del — the most
common CF-causing mutation — Asn1303Lys, and Ala561Glu. To correct the
misfolded proteins and help them reach the cell membrane, treatments called CFTR
correctors (which are a type of CFTR modulator) can be used.

Gating defects

The CFTR protein normally works as a gate at the cell’s surface. Some
mutations, such as Gly551Asp, Ser549Arg, and Gly1349Asp, lead to the production of
a protein for which the gate is “stuck closed.” These mutations are grouped in class III,
also one of the more severe disease types.

CFTR potentiators are a type of CFTR modulator that can treat gating
defects. These medications help keep the channels open for longer.

In other cases, the gate can open, but the protein is misshapen and only
allows a small amount of chloride ions to pass through. This reduction in chloride ion
movement is called decreased conductance and is grouped in class IV, one of the less
severe forms of CF. Examples of mutations that cause decreased conductance include
Arg117His, Arg334Trp, and Ala455Glu.

Decreased protein production

Sometimes a mutation can lead to CFTR protein being produced, but just
not in sufficient amounts working at the cell surface for long enough (class V). This is
caused by splicing mutations, which affect the cell’s ability to correctly read CFTR and
lead to relevant gene portions being left out. Meanwhile, others that are normally
excluded end up as part of the final RNA molecule.

Examples of this mutation type include 3272-26A→G and 3849+10 kg C→T.

31
 Treatment with a CFTR potentiator can be useful in treating mutations of
this type, by making the small amount of normal CFTR present at the cell membrane to
be open for a longer period.

Decreased protein stability

Some mutations cause the production of a CFTR protein that is functional,

but not stable, meaning it will degrade too quickly once on the cell surface. Examples
of such mutations, grouped in class VI, include c.120del123 and rF580del (F508del
after being rescued by correctors). Class VI also is considered a less-severe disease.

➢ Causes of Cystic Fibrosis

In cystic fibrosis, a defect (mutation) in a gene — the cystic fibrosis
transmembrane conductance regulator (CFTR) gene — changes a protein that regulates
the movement of salt in and out of cells. The result is thick, sticky mucus in the
respiratory, digestive and reproductive systems, as well as increased salt in sweat.

Many different defects can occur in the gene. The type of gene mutation is
associated with the severity of the condition.

Children need to inherit one copy of the gene from each parent in order to have
the disease. If children inherit only one copy, they won't develop cystic fibrosis.
However, they will be carriers and could pass the gene to their own children.

➢ Symptoms of Cystic Fibrosis

CF most commonly affects the lungs, causing respiratory symptoms, such as:

• wheezing
• shortness of breath
• persistent coughing, which may bring up blood or mucus
• other breathing difficulties

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 Also, in people with CF, the mucus that obstructs lung function creates optimal
living conditions for pathogens. As a result, a person has an increased risk of lung
infections, such as bronchitis and pneumonia.

CF symptoms can vary from person to person, depending on the affected organs.
Some other possible symptoms and complications are:

• frequent sinus infections

• gastrointestinal issues, such as:
o abdominal pain
o constipation
o diarrhoea
o greasy, foul-smelling stool
• nasal polyps, which are small, fleshy growths inside the nose
• salty skin and sweat
• night sweats
• fever
• jaundice
• joint and muscle pain
• low body weight
• limited growth or weight gain in children
• delayed puberty
• male infertility
• clubbed fingers and toes, due to a lack of oxygen to the extremities

The obstruction of the pancreas that can lead to malnutrition and limited
growth is also linked to an increased risk of diabetes and osteoporosis.

➢ Complications of Cystic Fibrosis

Complications of cystic fibrosis can affect the respiratory, digestive
and reproductive systems, as well as other organs.

Respiratory system complications

• Damaged airways (bronchiectasis). Cystic fibrosis is one of the leading causes

of bronchiectasis, a chronic lung condition with abnormal widening and scarring
of the airways (bronchial tubes). This makes it harder to move air in and out of
the lungs and clear mucus from the bronchial tubes.
33
 • Chronic infections. Thick mucus in the lungs and sinuses provides an ideal
breeding ground for bacteria and fungi. People with cystic fibrosis may often have
sinus infections, bronchitis or pneumonia. Infection with bacteria that is resistant
to antibiotics and difficult to treat is common.
• Growths in the nose (nasal polyps). Because the lining inside the nose is inflamed
and swollen, it can develop soft, fleshy growths (polyps).
• Coughing up blood (haemoptysis). Bronchiectasis can occur next to blood vessels
in the lungs. The combination of airway damage and infection can result in
coughing up blood. Often this is only a small amount of blood, but it can also be
life-threatening.
• Pneumothorax. In this condition, air leaks into the space that separates the lungs
from the chest wall, and part or all of a lung collapses. This is more common in
adults with cystic fibrosis. Pneumothorax can cause sudden chest pain and
breathlessness. People often feel a bubbling sensation in the chest.
• Respiratory failure. Over time, cystic fibrosis can damage lung tissue so badly
that it no longer works. Lung function usually worsens gradually, and it
eventually can become life-threatening. Respiratory failure is the most common
cause of death.
• Acute exacerbations. People with cystic fibrosis may experience worsening of
their respiratory symptoms, such as coughing with more mucus and shortness of
breath. This is called an acute exacerbation and requires treatment with
antibiotics. Sometimes treatment can be provided at home, but hospitalization
may be needed. Decreased energy and weight loss also are common during
exacerbations.

Digestive system complications

• Nutritional deficiencies. Thick mucus can block the tubes that carry digestive
enzymes from your pancreas to your intestines. Without these enzymes, your
body can't absorb protein, fats or fat-soluble vitamins, so you can't get enough
nutrients. This can result in delayed growth, weight loss or inflammation of the
pancreas.
• Diabetes. The pancreas produces insulin, which your body needs to use sugar.
Cystic fibrosis increases the risk of diabetes. About 20% of teenagers and 40%
to 50% of adults with CF develop diabetes.
• Liver disease. The tube that carries bile from your liver and gallbladder to your
small intestine may become blocked and inflamed. This can lead to liver
problems, such as jaundice, fatty liver disease and cirrhosis — and sometimes
gallstones.
• Intestinal obstruction. Intestinal blockage can happen to people with cystic
fibrosis at all ages. Intussusception, a condition in which a segment of the
34
 intestine slides inside an adjacent section of the intestine like a collapsible
telescope, also can occur.
• Distal intestinal obstruction syndrome (DIOS). DIOS is partial or complete
obstruction where the small intestine meets the large intestine. DIOS requires
urgent treatment.

Reproductive system complications

• Infertility in men. Almost all men with cystic fibrosis are infertile because the
tube that connects the testes and prostate gland (vas deferens) is either blocked
with mucus or missing entirely. Certain fertility treatments and surgical
procedures sometimes make it possible for men with CF to become biological
fathers.
• Reduced fertility in women. Although women with cystic fibrosis may be less
fertile than other women, it's possible for them to conceive and to have successful
pregnancies. Still, pregnancy can worsen the signs and symptoms of CF, so be
sure to discuss the possible risks with your doctor.

Other complications

• Thinning of the bones (osteoporosis). People with cystic fibrosis are at higher
risk of developing a dangerous thinning of bones. They may also experience joint
pain, arthritis and muscle pain.
• Electrolyte imbalances and dehydration. Because people with cystic fibrosis
have saltier sweat, the balance of minerals in their blood may be upset. This
makes them prone to dehydration, especially with exercise or in hot weather.
Signs and symptoms include increased heart rate, fatigue, weakness and low
blood pressure.
• Mental health problems. Dealing with a chronic illness that has no cure may
cause fear, depression and anxiety.

➢ Diagnosis of Cystic Fibrosis

The diagnosis of CF requires clinical symptoms consistent with CF in at
least one organ system and evidence of CFTR dysfunction. This evidence is usually
based on abnormal results from a sweat chloride test or the presence of mutations in the
CFTR gene.

35
 Clinical symptoms are not required for infants identified through new-born
screening. Other diagnostic tests that may be performed include:

• Immunoreactive trypsinogen (IRT) test: The IRT test is a standard new-born

screening test that checks the blood for abnormal levels of the protein called IRT.
A high level of IRT may be a sign of CF. However, further testing is required to
confirm the diagnosis.
• Sweat chloride test: The sweat chloride test is the most commonly used test for
diagnosing CF. It checks for increased levels of salt in the sweat. The test is
performed by using a chemical that makes the skin sweat when triggered by a
weak electric current. Sweat is collected on a pad or paper and then analysed. A
diagnosis of CF is made if the sweat is saltier than normal.
• Sputum test: During a sputum test, the doctor takes a sample of mucus. The
sample can confirm the presence of a lung infection. It can also show the types
of germs that are present and determine which antibiotics work best to treat them.
• Chest X-ray: A chest X-ray is useful for revealing swelling in the lungs due to
blockages in the respiratory passageways.
• CT scan.: A CT scan creates detailed images of the body using a combination of
X-rays taken from different directions. These images allow your doctor to view
internal structures, such as the liver and pancreas, making it easier to assess the
extent of organ damage caused by CF.
• Pulmonary function tests (PFTs): PFTs determine whether your lungs are
working properly. The tests can help measure how much air can be inhaled or
exhaled and how well the lungs transport oxygen to the rest of the body. Any
abnormalities in these functions may indicate CF.

➢ Treatment of Cystic Fibrosis

Although there’s no cure for CF, there are various treatments available that
may help relieve symptoms and reduce the risk of complications.

Medications

• Antibiotics. A doctor may prescribe antibiotics to get rid of a lung infection and
prevent a future infection. Antibiotics are usually given as liquids, tablets, or
capsules. In more severe cases, injections or infusions of antibiotics can be given
intravenously (through a vein).

36
 • Mucus-thinning medications. These make the mucus thinner and less sticky.
They also help you cough up the mucus so it leaves the lungs. This significantly
improves lung function.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). NSAIDs, such as ibuprofen
(Advil), have a limited role as an agent to reduce airway inflammation. The
Cystic Fibrosis Foundation suggests the use of high-dose ibuprofen in children
ages 6 through 17 with CF who have good lung function. Ibuprofen is not
recommended for people with more severe lung function abnormalities or those
who are older than age 18.
• Bronchodilators. Bronchodilators relax the muscles around the tubes that carry
air to the lungs, which helps increase airflow. You can take this medication
through an inhaler or a nebulizer.

Cystic fibrosis transmembrane conductance regulator (CFTR) modulators.

CFTR modulators are a class of drugs that can improve the function of the defective
CFTR gene. These drugs represent an important advance in the management of CF
because they target the function of the mutated CFTR gene rather than its clinical
effects. All patients with CF should undergo CFTR gene studies to determine if they
carry one of the mutations approved for CFTR modulator drugs. Most of the available
data are in patients less than 12 years old and in patients with mild or moderate CF lung
disease.

Surgical procedures

❖ Bowel surgery. This is an emergency surgery that involves the removal of a

section of the bowel. It may be performed to relieve a blockage in the bowels.
❖ Feeding tube. Cystic fibrosis may interfere with digestion and keep you from
absorbing nutrients from food. A feeding tube to supply nutrition can be passed
through the nose or surgically inserted directly into the stomach.
❖ Double lung transplant. When trying to medically manage your CF can no longer
maintain lung health and function, this procedure can improve the length and
quality of life for a person with CF.

Transplant Benefits

A lung transplant may be an option to improve and extend your life.

However, the CF gene mutation will remain in your body, affecting other organs even
after you’ve received new lungs.

There are also a number of things to consider when weighing

transplantation as an option. There’s a risk of infection and rejection of the organ, and

37
you will have to take medications that suppress your immune system for the rest of your
life.

Chest physical therapy

Chest therapy helps loosen the thick mucus in the lungs, making it easier to
cough up. It’s typically performed 1 to 4 times per day.

A common technique involves placing the head over the edge of a bed and
clapping with cupped hands along the sides of the chest.

Mechanical devices may also be used to clear mucus. These include:

• a chest clapper, which imitates the effects of clapping with cupped hands along
the sides of the chest
• an inflatable vest, which vibrates at a high frequency to help remove chest mucus

Home Care

CF can prevent the intestines from absorbing necessary nutrients from

food. If you have CF, you might need more calories per day than people who don’t the
disease. You may also need to take pancreatic enzyme capsules with every meal.

Your doctor may also recommend antacids, multivitamins, and a diet high
in fibre and salt. If you have CF, it’s important to:

• Drink plenty of fluids, because they can help thin the mucus in the lungs.
• Exercise regularly to help loosen mucus in the airways. Walking, biking, and
swimming are great options.
• Avoid smoke, pollen, and mould whenever possible. These irritants can make
symptoms worse.
• Get influenza and pneumonia vaccinations regularly.

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39
6.THALASSEMIA
Thalassemia is an inherited blood disorder in which the body makes an
abnormal form of haemoglobin. Haemoglobin is the protein molecule in red blood cells
that carries oxygen. The disorder results in excessive destruction of red blood cells,
which leads to anaemia. Anaemia is a condition in which your body doesn’t have
enough normal, healthy red blood cells. Thalassemia is inherited, meaning that at least
one of your parents must be a carrier of the disorder. It’s caused by either a genetic
mutation or a deletion of certain key gene fragments.

Thalassemia minor is a less serious form of the disorder. There are two
main forms of thalassemia that are more serious. In alpha thalassemia, at least one of
the alpha globin genes has a mutation or abnormality. In beta thalassemia, the beta
globin genes are affected. Each of these forms of thalassemia has different subtypes.
The exact form you have will affect the severity of your symptoms and your outlook.

➢ Types Of Thalassemia
There are three main types of thalassemia (and four subtypes):

• beta thalassemia, which includes the subtypes major and intermedia

• alpha thalassemia, which include the subtypes haemoglobin H and hydrops
fetalis
• thalassemia minor

▪ Thalassemia Beta

Beta thalassemia occurs when your body can’t produce beta globin.
Two genes, one from each parent, are inherited to make beta globin. This type of
thalassemia comes in two serious subtypes: thalassemia major (Cooley’s anaemia) and
thalassemia intermedia.

▪ Thalassemia Major

Thalassemia major is the most severe form of beta thalassemia. It

develops when beta globin genes are missing. The symptoms of thalassemia major
generally appear before a child’s second birthday. The severe anaemia related to this
condition can be life-threatening.

40
 Other signs and symptoms include:

• fussiness
• paleness
• frequent infections
• a poor appetite
• failure to thrive
• jaundice, which is a yellowing of the skin or the whites of the eyes
• enlarged organs

This form of thalassemia is usually so severe that it requires regular blood

transfusions.

▪ Thalassemia Intermedia

Thalassemia intermedia is a less severe form. It develops because of

alterations in both beta globin genes. People with thalassemia intermedia don’t need
blood transfusions.

▪ Thalassemia Alpha

Alpha thalassemia occurs when the body can’t make alpha globin. In order
to make alpha globin, you need to have four genes, two from each parent. This type of
thalassemia also has two serious types: haemoglobin H disease and hydrops fetalis.

❖ Haemoglobin H

Haemoglobin H develops as when a person is missing three alpha globin

genes or experiences changes in these genes. This disease can lead to bone issues. The
cheeks, forehead, and jaw may all overgrow. Additionally, haemoglobin H disease can
cause:

• jaundice
• an extremely enlarged spleen
• malnourishment

❖ Hydrops fetalis

Hydrops fetalis is an extremely severe form of thalassemia that occurs

before birth. Most babies with this condition are either stillborn or die shortly after being
born. This condition develops when all four alpha globin genes are altered or missing.

41
 ▪ Thalassemia Minor

In alpha minor cases, two genes are missing. In beta minor, one gene is
missing. People with thalassemia minor don’t usually have any symptoms. If they do,
it’s likely to be minor anaemia. The condition is classified as either alpha or beta
thalassemia minor.

Even if thalassemia minor doesn’t cause any noticeable symptoms, you can
still be a carrier for the disease. This means that, if you have children, they could
develop some form of the gene mutation.

➢ Causes Of Thalassemia
Thalassemia occurs when there’s an abnormality or mutation in one of
the genes involved in haemoglobin production. You inherit this genetic abnormality
from your parents.

If only one of your parents is a carrier for thalassemia, you may develop
a form of the disease known as thalassemia minor. If this occurs, you probably won’t
have symptoms, but you’ll be a carrier. Some people with thalassemia minor do develop
minor symptoms. If both of your parents are carriers of thalassemia, you have a greater
chance of inheriting a more serious form of the disease.

Thalassemia is most common in people from Asia, the Middle East,

Africa, and Mediterranean countries such as Greece and Turkey.

➢ Symptoms Of Thalassemia
The symptoms of thalassemia can vary. Some of the most common ones
include:

• bone deformities, especially in the face

• dark urine
• delayed growth and development
• excessive tiredness and fatigue
• yellow or pale skin

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 ➢ Complications Of Thalassemia

Possible complications of moderate to severe thalassemia include:

• Iron Overload. People with thalassemia can get too much iron in their bodies,
either from the disease or from frequent blood transfusions. Too much iron can
result in damage to your heart, liver and endocrine system, which includes
hormone-producing glands that regulate processes throughout your body.
• Infection. People with thalassemia have an increased risk of infection. This is
especially true if you've had your spleen removed.

In cases of severe thalassemia, the following complications can occur:

• Bone Deformities. Thalassemia can make your bone marrow expand, which
causes your bones to widen. This can result in abnormal bone structure,
especially in your face and skull. Bone marrow expansion also makes bones thin
and brittle, increasing the chance of broken bones.
• Enlarged Spleen. The spleen helps your body fight infection and filter unwanted
material, such as old or damaged blood cells. Thalassemia is often accompanied
by the destruction of a large number of red blood cells. This causes your spleen
to enlarge and work harder than normal. An enlarged spleen can make anaemia
worse, and it can reduce the life of transfused red blood cells. If your spleen
grows too big, your doctor might suggest surgery to remove it.
• Slowed Growth Rates. Anaemia can both slow a child's growth and delay
puberty.
• Heart Problems. Congestive heart failure and abnormal heart rhythms can be
associated with severe thalassemia.

➢ Diagnosis Of Thalassemia
If your doctor is trying to diagnose thalassemia, they’ll likely take a
blood sample. They’ll send this sample to a lab to be tested for anaemia and abnormal
haemoglobin. A lab technician will also look at the blood under a microscope to see if
the red blood cells are oddly shaped.

Abnormally shaped red blood cells are a sign of thalassemia. The lab
technician may also perform a test known as haemoglobin electrophoresis. This test
separates out the different molecules in the red blood cells, allowing them to identify
the abnormal type.
43
 Depending on the type and severity of the thalassemia, a physical
examination might also help your doctor make a diagnosis. For example, a severely
enlarged spleen might suggest to your doctor that you have haemoglobin H disease.

➢ Treatment For Thalassemia

The treatment for thalassemia depends on the type and severity of disease
involved. Your doctor will give you a course of treatment that will work best for your
particular case. Some of the treatments include:

• blood transfusions
• bone marrow transplant
• medications and supplements
• possible surgery to remove the spleen or gallbladder

Your doctor may instruct you not to take vitamins or supplements

containing iron. This is especially true if you need blood transfusions because people
who receive them accumulate extra iron that the body can’t easily get rid of. Iron can
build up in tissues, which can be potentially fatal.

If you’re receiving a blood transfusion, you may also need chelation therapy.
This generally involves receiving an injection of a chemical that binds with iron and
other heavy metals. This helps remove extra iron from your body.

44
 CHROMOSOMAL DISORDER

Chromosomes are thread-like structures present within the nucleus

that carry hereditary information within the sort of genes which are passed from parents
to offspring. Every species features a characteristic structure and number of
chromosomes present. Due to certain irregularities at the time of cell division, alteration
in the structure or number of chromosomes may happen. Even the slightest alteration
can lead to various abnormalities. Changes in one chromosome parts, whole
chromosome or chromosomal sets are known as “chromosomal aberrations”.

Chromosomal Disorders in Humans

There are 46 chromosomes in each human cell present as 23 pairs (n pairs),

out of which 22 are autosomes and 1 pair of sex chromosomes. Chromosomal disorders
are caused because of

• the structural changes

• numerical changes in chromosomes.

• Chromosomal Disorders Due to Numerical Abnormalities

Chromosomal disorders are caused due to the change in the number of chromosomes
present. This can be categorised into various types: -

o Aneuploidy: loss or gain of a chromosome. This happens due to non-disjunction

of chromatids when chromatids fail to separate during cell division. This results
in one gamete having two copies of one chromosome and the other having no
chromosome.
▪ Trisomy: The cell has one extra chromosome (2n+1)
▪ Monosomy: The cell has one chromosome less (2n-1)

Aneuploidy can be due to nondisjunction of autosomes i.e., chromosomes 1-

22 or sex chromosomes.

This is the cause of most of the genetically inherited disorders and abortion during
pregnancy

o Euploidy: Loss or gain of the entire set of chromosomes. Mostly occurs in plants.
o Haploid: Loss of one set of the chromosomes, i.e., ‘n’ number of chromosomes
45
 o Polyploid: Addition of one or more sets of chromosomes, e.g., ‘3n (triploid)’,
‘6n (hexaploid)’ etc.

• Chromosomal Disorders Due to Structural Abnormalities

This happens when an outsized set of genes are deleted, duplicated or

rearranged causing structural changes within the chromosome. Structural abnormalities
can be due to:

46
 o Deletion:

A portion of the chromosome is lost during cell division. A portion of the

chromosome without the centromere lags during anaphase movement and are lost from
reorganising nuclei or digested by nucleases. The resulting chromosome lacks certain
genes that get inherited by offspring. This condition is typically lethal thanks to missing
genes.

Deletions are often terminal, where a terminal portion of a chromosome

breaks leading to one break. Intercalary deletion, where an intermediate portion is lost
resulting from two breaks, which results in 3 pieces. The middle piece is lost and the
other two parts re-join

Example of Disorder Due to Deletion:

Cri du Chat (Cry of the Cat): There occurs of a small portion of the 5th chromosome.
Children with this disease have a small head with unusual facial features, severe mental
retardation and make a sound like a cat while crying.

o Duplication:

The presence of part of a chromosome in excess is known as duplication. If the

duplication is present only in one of the homologous pairs of a chromosome, the
duplicated part makes a loop to maximise the juxtaposition of homologous regions
during pairing. The extra segment is often arranged in many ways:

▪ Tandem duplication, where the duplicated region is present side by side

(ABCDEF→ABCDEF)
▪ The reverse tandem, here duplicated region is simply reverse of the traditional
sequence (ABCDEF→ABCDEF) plicated region isn't situated adjacent to the
traditional sequence.
▪ Transposed duplication is a way in which the duplicated part becomes attached
to a non-homologous chromosome.
▪ Extra-chromosomal duplication, here duplicated part acts as an independent
chromosome within the presence of centromere
▪ Example of Disorder Due to Duplication:

Fragile X: Affects 1:1500 males and 1:2500 females. This is the most common form of
mental retardation. Many people have around 29 repeats at the tip of the X chromosome.

o Inversion:

47
 Inversion results from breakage and reunion of a part of the chromosome
rotating by 180° on its own axis. So there occurs a rearrangement of genes. Its effects
are not as severe as in other structural defects.

o Translocation:

The shifting or transfer of a set of genes or part of a chromosome to a non-homologous

one is known as translocation. There is no addition or loss of genes, only the
rearrangement occurs. This rearrangement may lead to phenotype changes pertaining to
the new environment. It can cause difficulties in the development of eggs, sperm or
zygote. These often result in miscarriages and children born with disabilities.

▪ Reciprocal translocation, in this segment of two chromosome, gets interchanged

▪ Robertsonian translocation, here a whole chromosome attaches to a different
chromosome.

Example of Disorder Due to Translocation:

Acute Myelogenous Leukaemia: during this sort of cancer, bone marrow and cells
derived from it show the presence of a brief chromosome named as “Philadelphia (Ph1)
chromosome”. The 22nd chromosome loses a neighbourhood of its arm which gets
translocated to the distal end of the 9th chromosome. It is not transmitted to the
offspring.

Examples of chromosomal disorders in human beings:

1. Down’s Syndrome
2. Klinefelter’s Syndrome
3. Turner’s Syndrome

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1.Down’s Syndrome
It is a genetic disorder, which leads to various physical and mental disabilities.
It is due to the presence of an extra chromosome 21 also known as trisomy of
chromosome 21. Down syndrome is one of the leading causes of genetic disorders
around the world.

It is named after the physician Langdon Down, who first observed this
condition.

Other than physical attributes and mental retardedness, they are also
susceptible to various diseases like leukaemia and Alzheimer’s. There is no cure, only
the quality of life can be improved by taking extra care and training the individual to
perform daily essential activities. Down syndrome can be diagnosed during early
screening in pregnancy, which can decrease the occurrence of disease.

49
 ➢ Types Of Down’s Syndrome
Down syndrome is of three types:

i. Trisomy 21,
ii. Mosaicism
iii. Translocation

▪ Trisomy of chromosome 21:

Trisomy is the most common type of Down syndrome. It accounts for 95% of
cases of Down syndrome. There is one extra chromosome 21. The total number of
chromosome present is 47 instead of the normal 46 chromosomes.

The main cause of trisomy is Nondisjunction of chromosome 21 during

meiosis at the time of gamete formation. The abnormal cell with trisomy of
chromosome 21 is fertilised giving rise to trisomy in all the cells of the foetus.

▪ Mosaicism:

This is the rare form of Down syndrome, accounting for only 1% of the
total cases. In this type of Down Syndrome, some cells are normal having 46
chromosomes and some cells have abnormal 47 chromosomes. Symptoms may be less
prominent in mosaicism.

Mosaicism is caused when nondisjunction occurs during mitotic division in

the zygote after fertilization. It results in some normal cells and some cells with trisomy
of 21.

▪ Translocation Down Syndrome:

This type of Down syndrome accounts for 4% of the total cases. Here an extra
chromosome 21 is not present but there is an extra part of the chromosome 21 present
attached to a different chromosome. Total 46 chromosomes are present of which one is
abnormal.

This is due to the translocation of the long arm (q arm) of chromosome

21 to another chromosome during the replication process. The extra portion often gets
translocated to chromosome 14. So, a person with translocation Down syndrome
contains one chromosome 14, one chromosome 14/21 and a pair of normal chromosome
21. Its occurrence is not related to the mother’s age and it may run in families.

50
 ➢ Causes Of Down’s Syndrome
Down syndrome is a chromosomal disorder. It is due to aneuploidy of the
autosome. There is one extra chromosome 21 or part of the chromosome present in all
the cells or some cells. The occurrence of Down syndrome is 1:800 live births. The
major risk factor is the age of the mother. Most of the trisomy cases occur in the mother
having age more than 35.

Down syndrome is caused due to abnormal cell division. During mitotic

and meiotic cell division the chromosome pair separate so that each cell gets a copy of
each chromosome. In down syndrome, the chromosomes are not able to separate, giving
rise to cells with an unequal number of chromosomes. This phenomenon is called
nondisjunction.

Nondisjunction happens, when chromosome segregates in anaphase before

all of the replicated chromosomes’ kinetochores are attached to microtubules from
opposite poles during metaphase. It results in one daughter cell having one less
chromosome and another with one extra chromosome.

Down syndrome is also due to the translocation of a part of a chromosome

to another chromosome. The number of chromosomes is normal but one chromosome
has an extra part of chromosome 21. There is no genetic information missing in these
individuals but the extra copy of genes of chromosome 21 causes abnormal physical
and mental development.

Down syndrome is mostly not inherited. Translocation Down syndrome

can be passed from parent to child. It might be hidden in the parent due to balanced
translocation with no symptoms but can pass the unbalanced translocation to the child
and cause Down syndrome.

The life span of an individual with Down syndrome is around 60 years, it

depends on the number of health complications present.

➢ Symptoms Of Down’s Syndrome

Individuals with down syndrome are borne with many abnormalities. They
are found to have physical and mental disabilities. They have poor immunity and are
prone to get many diseases. They reach developmental milestones at a later age than
normal. Many times, they are found to be borne with congenital heart defects, thyroid

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disease, sleep apnea, gastrointestinal defects. They are more susceptible to get diseases
like leukaemia and Alzheimer’s.

People with down syndrome can be easily identified by their physical attributes
and facial features. Slowly after they are borne different symptoms start appearing.
Infants may be of normal size but as they grow slowly, their height remains much less
than those of the same age. The main symptoms of Down syndrome are:

• Short stature and stunted growth

• Fold of the skin above the eye, slanted eyes
• Protruding furrowed tongue, flattened nose
• Mental retardation
• Cardiac deformities
• Single transverse palm crease and hand is broad and short
• Poor muscle tone and excessive flexibility
• Small head, short neck and abnormal teeth
• Delay in language development
• Cognitive impairment may be mild to moderate

➢ Complications Of Down Syndrome

Babies with Down syndrome may be born with other physical problems, and
they’re at higher risk for certain health issues later in life.

Possible complications of Down syndrome include:

• Heart problems. About half of babies with Down syndrome are born with a heart
defect that may need surgery.
• Hearing and vision problems, including crossed eyes and cataracts
• Gastrointestinal disorders, like blockages, reflux, and celiac disease
• Obesity
• Breathing issues, including sleep apnea, asthma, and pulmonary hypertension
• Underactive thyroid
• Seizures
• Childhood leukemia
• Early-onset dementia

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 ➢ Diagnosis Of Down’s Syndrome
Children with Down syndrome can be diagnosed before or after birth. Due
to peculiar facial features, they are easily identifiable. If diagnosed after birth, there is
no cure available and only quality of life can be improved by training, education and
extra care.

Down syndrome can be diagnosed during pregnancy and if the foetus is

found to have Down syndrome, pregnancy is terminated.

Down syndrome can be diagnosed by the amniocentesis technique. In

amniocentesis, the amniotic fluid is taken out with the help of a needle and the
karyotype of the dividing cells are done in the lab. Cells of amniotic fluid have the same
genetic content as the foetus. The karyotype is studied for any chromosomal
abnormality. If the karyotype is abnormal, the foetus is aborted.

➢ Treatment Of Down’s Syndrome

There’s no cure for Down syndrome, but there’s a wide variety of support
and educational programs that can help both people with the condition and their
families. The NDSS is just one place to look for programs nationwide.

Available programs start with interventions in infancy. Federal law requires

that states offer therapy programs for qualifying families. In these programs, special
education teachers and therapists will help your child learn:

• sensory skills
• social skills
• self-help skills
• motor skills
• language and cognitive abilities

Children with Down syndrome often meet age-related milestones. However,

they may learn more slowly than other children.

School is an important part of the life of a child with Down syndrome,

regardless of intellectual ability. Public and private schools support people with Down
syndrome and their families with integrated classrooms and special education

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opportunities. Schooling allows valuable socialization and helps students with Down
syndrome build important life skills.

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2.Klinefelter’s Syndrome
Klinefelter syndrome is one of the genetic disorders in males. It occurs
when a male baby is born with more than required or extra X chromosomes. Many
males consist of one X and one Y chromosome and an extra chromosome can cost a
male with physical traits which are inappropriate for males.

Klinefelter syndrome is found in 1 out of 1000 males. The unwanted

additional sex chromosome is a result of a random error in the formation of sperm or
the egg.

More than half of the time the error happens in the sperm formation while
the remainder is due to complications in the egg development. Women with pregnancies
after the age of 35 have slightly more chances of having a baby with this syndrome.

A complete picture of a person’s chromosomes is referred to as a

karyotype. Any changes in this karyotype results in the chromosomal abnormalities and
Klinefelter syndrome is one among the chromosomal abnormalities with the presence
of additional or an extra X chromosome in boys.

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 ➢ Types of Klinefelter Syndrome
Types of Klinefelter syndrome are divided into 3:

▪ Classical Type Klinefelter Syndrome

The most frequently observed Klinefelter type is the condition that the X
chromosome, which is called classical and is observed in 80% of patients, has an extra
copy in each cell.

▪ Mosaic Type Klinefelter Syndrome

The state of mosaic Klinefelter syndrome, which is observed in approximately

20% of patients and that only some cells have extra X chromosomes. Symptoms of this
type are milder and less pronounced.

▪ Barr-Shaver-Carr syndrome

Very rarely, multiple extra X chromosomes can be observed in Klinefelter

syndromes. In such cases, symptoms manifest more seriously.

➢ Causes Of Klinefelter’s Syndrome

Everyone is born with 23 pairs of chromosomes, or 46 chromosomes in
total, inside each of their cells. These include two sex chromosomes, X and Y.

• People who are born female have two X chromosomes, XX. These chromosomes
give them sexual traits like breasts and a uterus.
• People who are born male have one X and one Y chromosome, XY. These
chromosomes give them traits such as a penis and testicles.

People with Klinefelter syndrome are born with an extra X, causing their
cells to have XXY chromosomes. This happens randomly during conception. About
half the time the extra chromosome starts in the mother’s egg. The other half of the time
it comes from the father’s sperm.

Some people with the syndrome have more than one extra X chromosome.
For example, their chromosome might look like this: XXXXY. Others have different
chromosome abnormalities in each cell. For example, some cells might be XY, while
others are XXY. This is called mosaicism.
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 ➢ Symptoms Of Klinefelter’s Syndrome
The symptoms of Klinefelter syndrome can vary. While some people will
have no discernible symptoms and have no idea they’re living with the syndrome, others
may deal with a variety of symptoms.

Symptoms In Babies

When present, many of the symptoms of Klinefelter syndrome in

young children and babies may go overlooked because they aren’t always obvious —
especially because child development can be very individualized. However, you may
want to talk with your child’s paediatrician if these symptoms are present and concern
you:

• a delayed start in learning to crawl or walk

• a delayed start in talking
• a seemingly quieter, or more passive attitude
• Symptoms in young males and teens

The symptoms of Klinefelter syndrome are often most obvious in

tween and teen males due to the onset of puberty. It’s important to follow your instincts
if you, or they, are worried something is amiss. Some of the symptoms of the Klinefelter
syndrome in tween and teens are:

• mild dyslexia
• issues with paying attention
• lowered energy levels
• difficulty socializing
• delayed puberty, which can include:
▪ a lack of facial or body hair
▪ a higher pitched voice
▪ more fat deposits around the hips and buttocks, creating a rounder
lower half of the body
• enlarged breasts (gynecomastia)
• taller stature than the rest of the family (including long arms and legs)
• difficulty increasing or producing muscle tone
• smaller testicles
• smaller penis

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Symptoms In Adults

The main symptom in adults is often fertility difficulties — although there

are many treatments available for this symptom.

Adult males who only have an extra X chromosome in some of their cells
will have milder symptoms. A smaller number of males have more than one extra X
chromosome in their cells. The more X chromosomes they have, the more severe their
symptoms may be.

Symptoms Of More Severe Klinefelter Types Include:

• major problems with learning and speech

• poor coordination
• unique facial features
• bone problems

➢ Complications Of Klinefelter Syndrome

Many problems caused by Klinefelter are because of lower testosterone levels.
You may have a slightly higher chance of:

• Autoimmune problems, such as lupus and rheumatoid arthritis, in which your

immune system attacks healthy parts of your body
• Breast cancer and cancers that affect your blood, bone marrow, and lymph nodes
• Conditions with your hormone glands, such as diabetes
• Heart disease and problems with blood vessels
• Lung disease
• Mental health problems, such as anxiety and depression
• Weak bones, called osteoporosis

➢ Diagnosis Of Klinefelter’s Syndrome

A small number of males with Klinefelter syndrome receive a diagnosis
before birth when their mother has one of these tests:

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 o Amniocentesis. During an amniocentesis, a technician removes a small amount
of amniotic fluid from the sac surrounding the baby. The fluid is then examined
in a lab for chromosome problems.
o Chorionic villus sampling. Cells from tiny finger-like projections called
chorionic villi in the placenta are removed during a chorionic villus sampling.
These cells are then tested for chromosome problems.

Because these tests can increase the risk for a miscarriage, they usually aren’t
done unless the baby is at risk for a chromosome problem. Often, Klinefelter syndrome
isn’t discovered until a child reaches puberty or later.

If your child seems like they’re developing slowly and it feels concerning, talk
with your child’s paediatrician. They may refer you to an endocrinologist. This doctor
specializes in diagnosing and treating hormonal conditions.

During the exam, your doctor will ask about any symptoms or development
issues you or your child has. The main test used to diagnose Klinefelter syndrome is:

o Chromosome analysis. Also called karyotyping, this blood test checks for
abnormal chromosomes, such as an extra X chromosome.

➢ Treatment Of Klinefelter’s Syndrome

There are different types of treatment available for the Klinefelter syndrome
and based on signs and symptoms of the patients the treatment varies. The treatment
includes:

• Fertility treatment.
• Psychological counselling.
• Removal of excess breast tissue.
• Hormonal Replacement Therapy.
• Support and Educational evaluation.

Males affected by Klinefelter syndrome are given testosterone, which is a male

sex hormone required for sexual enhancement. If the treatment begins near the age of
puberty, it can serve boys to have proper body development.

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 The testosterone is injected through a gel or skin patch. Normally the treatment
prolongs throughout a man’s life, but does not assist infertility. Educational support and
Speech therapy can be helpful for boys with problems in language.

A man is capable of having his sperm gathered via testicular sperm extraction
(TEST) if he wants to have children. The sperms are obtained during the TEST by
inserting a clean needle within the testicle or a small cut formed in the testicle. Normal
sperm is found and used in vitro fertilization.

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3.Turner’s Syndrome
Turner syndrome is a genetic disorder in females, it is due to the partial or
complete loss of one of the X chromosomes. Turner syndrome is also known as
monosomy of the X chromosome. Turner syndrome leads to various developmental
problems and people with Turner syndrome are at risk of many diseases.

In 1938, Henry H. Turner described the condition first hence the name
Turner syndrome. Turner syndrome is the only viable monosomic chromosomal
anomaly.

Turner syndrome causes retarded sexual development in females. They are

mostly sterile with short stature and webbing of the skin in the neck region is present.
Apart from these, there may be cardiac abnormalities, hearing impairment, vision loss,
etc. may be present in a person with Turner Syndrome. There is no cure because it is a
genetic disorder, but treatment may help in resolving issues such as learning difficulties,
short stature and sexual development. Turner syndrome can be diagnosed by antenatal
tests during pregnancy. Karyotype also confirms Turner Syndrome.

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 ➢ Symptoms Of Turner’s Syndrome
People assigned female at birth with Turner syndrome can exhibit certain
characteristics during infancy and in childhood, as well as into adulthood.

Many of these symptoms can be vague and aren’t always easy to

immediately connect to Turner syndrome. If you are concerned with your child’s
development at any stage, it’s a good idea to talk with their paediatrician.

Infancy

• Some signs of Turner syndrome during infancy include:

• small size
• swelling of hands and feet
• extra folds in the neck
• heart abnormalities
• difficulty with feeding
• Childhood and teenage years

As a person grows up, the signs of Turner syndrome may become a bit more
obvious. Some of these signs include:

• smaller in stature than most of their peers

• below average in both height and weight
• chronic ear infections
• hearing issues
• learning difficulties

One of the main symptoms of Turner syndrome is the underdevelopment of

the ovaries. Because the ovaries are responsible for producing sex hormones, this
underdevelopment can slow or stop the typical signs of puberty, such as breast
development and menstruation, in people assigned female at birth.

Hormone therapy, such as estrogen, can help with breast development and
increase the size of the uterus. It can also help with height development.

Adulthood

If Turner syndrome is not treated earlier, or if a person is living with a severe

form of it, some of the symptoms in adulthood can include:

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 • irregularities in menstrual cycle
• hearing issues
• heart issues
• small stature

Having one or more of these symptoms doesn’t necessarily mean that you or
your child has Turner syndrome. However, it’s always a good idea to speak with a
doctor if you feel as though something is amiss when it comes to your health or the
development of your child.

➢ Complications Of Turner’s Syndrome

People with Turner syndrome are at a higher risk of certain medical problems.
With appropriate monitoring and regular check-ups, however, most of the conditions
can be managed.

• Kidney abnormalities. Kidney abnormalities are common in people with Turner

syndrome. Some people with Turner syndrome also have recurrent urinary tract
infections (UTIs). This is because the kidneys may be irregularly formed or in
the wrong position in the body.
• High blood pressure. High blood pressure can occur due to these kidney
abnormalities.
• Hypothyroidism. Hypothyroidism, a condition where you have low levels of
thyroid hormone, is another possible complication. It can be caused by the
inflammation of the thyroid gland, which can occur in some people with Turner
syndrome.
• Celiac disease. Celiac disease can often occur in people with Turner syndrome,
as these individuals have a higher-than-average risk of developing it. Celiac
disease causes the body to have an allergic reaction to the protein gluten, which
is found in foods like wheat and barley.
• Heart abnormalities. Heart abnormalities are common in people with Turner
syndrome. People with the condition should be monitored for problems with
their aorta (the main artery connecting the heart and the rest of the body) and
high blood pressure.
• Lymphedema. Lymphedema, which is swelling due to fluid retention, can often
occur in the hands and feet of people with Turner syndrome.

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 ➢ Diagnosis Of Turner’s Syndrome
Prenatal genetic testing done before birth can help a doctor diagnose Turner
syndrome. The condition is identified through a laboratory procedure called
karyotyping. When performed during prenatal testing, karyotyping can detect if the
mother’s chromosomes have any genetic abnormalities.

Your doctor may also order tests to look for the physical symptoms of Turner
syndrome. These tests may include:

• blood tests to check sex hormone levels

• echocardiogram to examine for heart defects
• pelvic exam
• pelvic and kidney ultrasound
• chest MRI scan
• Turner syndrome treatment

If you’ve been diagnosed with Turner syndrome, you can still lead a full, happy
life. While there is no cure, there are treatments that can help manage symptoms and
improve your quality of life.

Growth hormone therapy may help children with Turner syndrome grow taller.
These daily injections usually start around ages 5 or 6 and end when a person is around
15 or 16.

Estrogen and progesterone replacement therapy is another possible treatment.

These hormone replacements can aid in the development of secondary sex
characteristics like breasts and pubic hair and can help keep periods more regular. These
hormone replacements are usually given at the start of puberty and may need to be
continued for most of a person’s adult life.

While some people with Turner syndrome may be able to conceive a child,
many individuals with this rare condition may have more difficulty. Assisted conception
techniques like in vitro fertilization (IVF) and egg donation are two possible solutions.

Both family support and the support of a therapist or group can be very
beneficial for people living with Turner syndrome — especially if the person is living
with learning differences or emotional stressors from their symptoms.

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 ➢ Treatment for Turner’s Syndrome
There is no cure for Turner syndrome. Whatever treatment is done, it is for
complications related to Turner syndrome such as sexual development, hearing and
vision impairment, infertility.

Preventive care can keep conditions such as heart complications and

thyroid under check.

Hormone therapy is useful for short stature, inducing sexual development

and reducing the risk linked to it.

IVF can help if a female with Turner syndrome wishes to get pregnant.

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 CONCLUSION

Gregor Mendel the father of genetics postulated his three Laws of

Inheritance, which eventually became the basis of modern-day genetics. These laws
namely “Law of Dominance”, “Law of Segregation” & “Law of Independent
Assortment” can be used to analyse types of genetic disorders and inheritance
patterns. Pedigree charts, made based on Mendel’s Laws can be used to analyse and
study Inheritance patterns of different genes in a family hence helping in diagnosing
and curing several genetic disorders.

On the whole genetics, an endless study has helped us, human beings to
understand ourselves in way that is unimaginable. The vastness of this study is far
greater than anything known to man and now as this study deepens into the vastness
perhaps there is hope in the future for a society free from any kind of disease and
sufferings.

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 BIBLIOGRAPHY

Following websites and books were a source for this project:

1. www.Google.com
2. www.wikipedia.com
3. www.seminarsonly.com
4. NCERT Biology text of class XII

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