MENDELIAN

DISORDERS
INTRODUCTION
Regor Mendel’s studies on pea plants to determine inheritance
patterns laid the groundwork for our current understanding of
single-gene diseases in humans, which is still being built upon
today. Mendelian diseases, also known as monogenic diseases,
are caused by mutations in a single gene. Sometimes they are
passed down through families. Mendelian disorders are caused by
a single genetic mutation that occurs at a single genetic locus. An
autosome or a sex chromosome could contain this gene’s coding
sequence. Either a dominant or recessive model can be used to
describe the disorder’s manifestation. In large families with many
affected individuals, we can determine whether a disease-
associated gene is present on an autosome or on a sex
chromosome by performing pedigree analysis on the genes
involved in the disease. It is also used to determine whether a
particular phenotype is dominant or recessive in nature.

Online Mendelian Inheritance in Man (OMIM), an authoritative

database of inherited human conditions, identifies some 4000
mendelian disorders. Some of the better known conditions are
listed in Table 4. Frequencies given in this table are very
approximate, and can vary markedly depending on ethnicity.
Where the illness is predominant in a particular ethnic group, this
is indicated. Although birth frequencies are cited here, for some
conditions the intervention of carrier screening and
prenatal DNA diagnosis is reducing these frequencies significantly.
Examples of successful reductions in genetic disease through this
approach are Tay–Sachs in the Jewish community and β-
thalassaemia in some Mediterranean areas. See also Genetic
Screening and Testing, Inherited Diseases of Intermediary

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Metabolism: Molecular Basis, Prenatal Diagnosis,
and Thalassaemias

sickle cell anaemia

INTRODUCTION
Sickle Cell Anaemia is a type of autosomal recessive genetic
disorder and its inheritance pattern follows the inheritance from
two carrying parents. Sickle cell anaemia is the most common
form of Sickle cell disease(SCD). Sickle cell disease is a group of
inherited red blood cell disorders that affect haemoglobin, the
protein that carries oxygen through the body. Normally, red blood
cells are disc-shaped and flexible enough to move easily through
the blood vessels. In sickle cell disease, red blood cells become
crescent- or “sickle”-shaped due to a genetic mutation. These
sickled red blood cells do not bend or move easily and can block
blood flow to the rest of the body. The blocked blood flow through
the body canlead to serious problems, including stroke, eye
problems, infections,and episodes of pain called pain crises.
Sickle cell disease is a lifelong
illness.

The figure shows the difference

between Normal red blood cell and
Sickle cell .The Cross section of
normal red blood cell shows
unrestricted blood flow whereas the
cross section of sickle cell shows blocking blood flow in a blood
vessel.

Overview
 Sickle cell anaemia is one type of anaemia. Anaemia is a
condition in which your blood has a lower number of red

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 blood cells. This condition can also occur if your red blood
cells don’t contain enough haemoglobin.
 Red blood cells are made in the spongy marrow inside the
larger bones of the body. Bone marrow is always making new
red blood cells to replace old ones. Normal red blood cells
live about 120 days in the bloodstream and then die. They
carry oxygen and remove carbon dioxide from body.
 In sickle cell anaemia ,the abnormal sickle cells usually die
after only about to 10 to 20 days. The bone marrow can’t
make new red blood cells fast enough to replace the dying
ones.
 Sickle cell anaemia is an inherited ,lifelong disease. People
who have the disease are born with it. They inherit two genes
for sickle cell haemoglobin- one from each parent.
 Sickle Cell Anaemia is caused when valine(Val) replaces the
glutamic acid (Glu) in the sixth position of the β-globin chain
of the haemoglobin molecule. Due to this mutation, the
biconcave shape of the haemoglobin molecule undergoes
physical change and converts into the sickle shape. This
mutation results in the reduction of the oxygen-binding
capacity of the haemoglobin molecule.

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 SICKLE CELL MUTATION
Causes 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.

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Sickle Cell Trait
 People who inherit a sickle haemoglobin gene from one
parent and a normal gene from other parent have sickle cell
trait(SCT). Their bodies make both sickle haemoglobin and
normal haemoglobin.
 People with SCT usually do not have
any of the symptoms of sickle cell
disease (SCD), but they can pass the
trait on to their children. However,
some people may have medical
complications. The following image
shows an example of an inheritance
pattern for sickle cell trait.

The image shows how sickle cell

haemoglobin genes are inherited .When
both parents gave a normal gene and an abnormal gene ,each child
has a 25% chance of inheriting two normal genes; 50% chance of
inheriting one normal gene and one abnormal .

Signs and Symptoms of Sickle Cell Anaemia

Signs and symptoms of sickle cell anaemia usually appear around 6 months of
age. They vary from person to person and may change over time. The most
common signs and symptoms are linked to anaemia and pain.

Sign and Symptoms Related to

Anaemia

The most common symptom of

anaemia is fatigue(feeling tired
or weak).Other signs and
symptoms of anaemia include:

• Shortness of breath
• Dizziness

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 • Headache
• Coldness in the hands and feet
• Paler than normal skin or mucous membranes (the tissue
that lines your nose, mouth and other organs and body
cavities)
• Jaundice (yellowish colour of skin or whites of the eyes)

Diagnosis of Sickle cell anaemia

1.PRENATAL SCREENING
Sickle cell disease can be diagnosed in an unborn baby by sampling
some of the fluid surrounding the baby in the mother's womb
(amniotic fluid). Testing before birth can be done as early as 8 to
10 weeks into the pregnancy. This testing looks for the sickle
haemoglobin gene rather than the abnormal haemoglobin itself.
This testing cannot predict the severity of the disease .

2.NEWBORN SCREENING
In newborn screening programs, drops of blood from a heel prick
are collected on a special type of paper. The haemoglobin from
this blood is then tested in a lab. Newborn screening results are
sent to the provider who ordered the test and to your child’s
healthcare provider.

3. GENETIC TESTING
Genetic testing, usually through DNA analysis, can confirm the
presence of specific genetic mutations associated with sickle cell
anaemia. The most common genetic mutations are HbS, which
results from a point mutation in the HBB gene on chromosome
11.

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4. ADDITIONAL TESTS
 X-rays, ultrasounds, and other imaging studies may be
performed to assess the extent of organ damage or
complications caused by sickle cell anaemia.
 It's important to note that sickle cell anaemia is a genetic
condition, so it can be diagnosed in infants through newborn
screening or later in life if symptoms develop. Early
diagnosis and regular medical follow-up are crucial for
managing the condition and preventing complications.
Treatment options may include medications, blood
transfusions, and stem cell transplantation, depending on
the severity of the disease. A haematologist or a medical
specialist with expertise in blood disorders typically
manages the care of individuals with sickle cell anaemia.

HAEMOPHILIA
INTRODUCTION
 Haemophilia is a rare bleeding disorder in which the blood
doesn't clot in the typical way because it doesn't have
enough blood-clotting proteins (clotting factors). If you have
haemophilia, you might bleed for a longer time after an
injury than you would if your blood clotted properly.
 Haemophilia is also referred to as
Royal disease because it is common in
royal families of Europe. The disease
spread in the royal families through the
children of Queen Victoria. The queen's
ancestors were not infected with the
disease. The haemophilia gene

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 appears to have originated through mutation in either her
father's or her own germ cells

Overview
Haemophilia is primarily an inherited condition. “Inherited”
means that the disorder is passed from parents to children
through genes. People born with haemophilia have little or no
clotting factor. Clotting factor is a protein needed for normal
blood clotting. There are several types of clotting factors. There
are two main types of haemophilia:

1. Haemophilia A: This is the most common type of

haemophilia and is caused by a deficiency of clotting factor VIII
(FVIII). Haemophilia A is also known as "classic haemophilia."
2. Haemophilia B: Also known as Christmas disease,
haemophilia B is caused by a deficiency of clotting factor IX (FIX).

Rarely, Haemophilia can be acquired. Acquired means you aren’t

born with the disorder, but you develop it during your lifetime.
This happen if your body forms antibodies that attack the clotting
factors in your bloodstream. The antibodies can prevent the
clotting factors from working.

Causes of Haemophilia
 In the most common types of
haemophilia, the faulty gene
is located on the X
chromosome. Everyone has
two sex chromosomes, one
from each parent. Females
inherit an X chromosome
from the mother and an X
chromosome from the father.
Males inherit an X

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 chromosome from the mother and a Y chromosome from the
father.
 This means that haemophilia almost always occurs in boys
and is passed from mother to son through one of the
mother's genes. Most women with the defective gene are
carriers who have no signs or symptoms of haemophilia. But
some carriers can have bleeding symptoms if their clotting
factors are moderately decreased.

Signs and Symptoms of Haemophilia

Common signs of haemophilia include:

• Bleeding into the joints. This can cause swelling and

pain or tightness in the joints; it often affects the knees,
elbows, and ankles.
• Bleeding into the skin
(which is bruising) or
muscle and soft tissue
causing a build-up of
blood in the area (called
a hematoma).
• Bleeding of the mouth
and gums, and bleeding
that is hard to stop after
losing a tooth.
• Bleeding after circumcision.
• Bleeding after having shots, such as vaccinations.
• Bleeding in the head of an infant after a difficult delivery.
• Blood in the urine or stool.
• Frequent and hard-to-stop nosebleeds.

Diagnosis of Haemophilia
o Severe cases of haemophilia usually are diagnosed within
the first year of life. Mild forms might not be apparent until

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 adulthood. Some people learn they have haemophilia after
they bleed excessively during a surgical procedure.
o Clotting-factor tests can reveal a clotting-factor deficiency
and determine how severe the haemophilia is.
o For people with a family history of haemophilia, genetic
testing might be used to identify carriers to make informed
decisions about becoming pregnant.
o It's also possible to determine during pregnancy if the foetus
is affected by haemophilia. However, the testing poses some
risks to the foetus. Discuss the benefits and risks of testing
with your doctor.

THALASSEMIA
INTRODUCTION
Thalassemia is an inherited (i.e., passed from parents to children
through genes) blood disorder caused when the body doesn’t
make enough of a protein called haemoglobin, an important part
of red blood cells. Thalassemia is a treatable disorder that can be
well-managed with blood transfusions and chelation therapy. It is
important for people with thalassemia to learn how to stay
healthy.

Overview
 Normal haemoglobin, also called haemoglobin A, has four
protein chains—two alpha globin and two beta globin. The
two major types of thalassemia, alpha and beta, are named
after defects in these protein chains.
 Four genes (two from each parent) are needed to make
enough alpha globin protein chains. Alpha thalassemia trait
occurs if one or two of the four genes are missing. If more
than two genes are missing, moderate to severe anaemia
occurs.

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  The most severe form of alpha thalassemia is called alpha
thalassemia major or hydrops fetalis. Babies who have this
disorder usually die before or shortly after birth.
 Two genes (one from each parent)
are needed to make
enough beta globin
protein chains. Beta
thalassemia occurs if one
or both genes are altered.
The severity of beta
thalassemia depends on
how much one or both
genes are affected. If both
genes are affected, the
result is moderate to
severe anaemia. The severe form of beta thalassemia is
known as thalassemia major or Cooley's anaemia.
 Thalassemia affects males and females. The disorders occur
most often among people of Italian, Greek, Middle Eastern,
Southern Asian, and African descent. Severe forms usually
are diagnosed in early childhood and are lifelong conditions.
 Doctors diagnose thalassemia using blood tests. The
disorders are treated with blood transfusions, medicines,
and other procedures.

Causes of Thalassemia
 Thalassemia is generally caused due to the abnormality in
one of the genes which were involved in the haemoglobin
production and this abnormality is inherited by the children
from their parents. The oxygen is transported to the entire
body by the blood
cells are done with
the help of protein
haemoglobin. The
Bone Marrow then

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 uses the iron that is obtained from food to make
haemoglobin.
 People suffering from thalassemia do not have enough
haemoglobin in their body as the bone marrow fails to
produce the required amount of haemoglobin that leads to
lack of oxygen and results in further diseases like fatigue &
anaemia. Severe level of thalassemia requires regular blood
transfusions.

Here are the primary causes of these two types of

thalassemia:

1. Alpha Thalassemia

 As the name suggests, alpha thalassemia occurs when there

is a
defective
formation of
alpha globin
chain. In this
disorder,
there is
decreased
synthesis of

resulting in an excess of β globin chains in adults and 𝛾

α globin,

(gamma) chains in newborns. As a result, haemoglobin

tetramers are unstable and there is abnormal oxygen
dissociation curve.
 This condition is controlled by two genes that are present on
chromosome 16. These two genes are HBA1 and HBA2 and
they collectively have four alleles. Silent carriers have one
defective allele, while those with two defective alleles have
thalassemia minor with mild anaemia.
 A person with three defective alleles is likely to develop the
haemoglobin H or HbH disease which is characterised by

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 anaemia, enlargement of spleen and liver, jaundice,
overgrowth of upper jaw and forehead, etc.
 In case, all the four alleles are defective, the foetus develops
hydrops foetalis which is an excessive buildup of fluid in the
foetal body. This is accompanied with anaemia, enlarged
liver and spleen, heart defects, abnormalities in the urinary
system and genitalia. The mother often develops high blood
pressure with swelling. Delivery is generally premature and
associated with abnormal blood loss. The child is either still
born or dies soon after delivery.

2. Beta Thalassemia
In this condition, there is a decreased synthesis of β globin chain.
The defect occurs on the alleles of the HBB gene present on
chromosome 11. Thalassemia minor is characterised by a higher
number of microcytic (smaller than usual) erythrocytes and a
lower amount of haemoglobin in those who have one faulty
allele. On the contrary, if a person has both the defective alleles
then it results in Cooley’s anaemia or thalassemia major.

Signs and Symptoms of Thalassemia

A lack of oxygen in the bloodstream causes the signs and
symptoms of thalassemia. The lack of oxygen occurs because the
body doesn't make enough healthy red blood cells and

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haemoglobin. The severity of symptoms depends on the severity
of the disorder.

• No Symptoms
Alpha thalassemia silent carriers generally have no signs or
symptoms of the disorder. The lack of alpha globin protein is so
minor that the body's haemoglobin works normally .

• Mild Anaemia
People who have alpha or beta thalassemia trait can have mild
anaemia. However, many people who have these types of
thalassemia have no signs or symptoms.
Mild anaemia can make you feel tired. Mild anaemia caused by
alpha thalassemia trait might be mistaken for iron-deficiency
anaemia.

• Mild to Moderate Anaemia

People who have beta thalassemia intermedia have mild to
moderate anaemia. They also may have other health problems,
such as:

1. Slowed Growth and Delayed Puberty

2. Bone Problems
3. An Enlarged Spleen
• Severe Symptoms
People who have haemoglobin H disease or beta thalassemia
major (also called Cooley's anaemia) have severe thalassemia.
Signs and symptoms usually occur within the first 2 years of life.

They may include severe anaemia and other health problems,

such as:

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 • A pale and listless appearance
• Poor appetite
• Dark urine (a sign that red blood cells are breaking down)
• Slowed growth and delayed puberty
• Jaundice (a yellowish colour of the skin or whites of the eyes)
• An enlarged spleen, liver, or heart
• Bone problems (especially with bones in the face)

Diagnosis of Thalassemia
Few of the diagnosis are done by doctors to check the level of
severity of thalassemia & blood tests to detect if the individual is
having the disease or not. Some of those diagnoses are:

• Genetic Testing: In this, DNA analysis with which it will be

detected whether a person has thalassemia or faulty genes

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• Prenatal Testing: This shows whether a foetus is having
thalassemia and its level of severity. It is done in two
processes:
1. Amniocentesis in which sample of amniotic fluid is taken
for testing in the 16th week of pregnancy. It is the fluid
which surrounds the foetus.
2. Chronic Villus Sampling (CVS) in which piece of placenta
is removed for testing purpose during the 11th week of
pregnancy.

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 COLOUR BLINDNESS
INTRODUCTION
Colour blindness, also known as Colour Vision Deficiency
(CVD), is a syndrome which was discovered in the year 1798 by
an English chemist named 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 may
not be able to visualize, see and identify any colours at all. 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.

Overview
▪ Colour blindness is a recessive sex-linked trait. The colour-
blind person is unable to distinguish red and green colours.
The vision of a person is not affected. The gene responsible
for normal vision is generally dominant. The normal gene
and the recessive allele,
both are carried by
Xchromosomes. A
female become colour
blind, when both the sex
chromosomes carry
recessive gene (XcXc). As
the disease is not lethal,
colourblind females survive and do not die before birth.
▪ It is a sex-linked recessive disorder that occur due to defect
in either red or green cone cells of an eye. As a result, a
person is unable to distinguish between red and green
colour. It results from a mutation in a gene, responsible for
colour vision, in the X-chromosome.
▪ It occurs in about 8 percent of males and about 0.4 percent
of females. This is because males have only one X
chromosome and females have two.

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 ▪ The son of a woman who carries the gene has a 50% chance
of being colour blind.

Causes of Colour Blindness

There are two types of cells in the human eye that help in vision.
These are rod cells and cone cells. The rod cells help in vision in
dim and dark conditions and the cone cells help in colour vision
under bright light. Cone cells are able
to differentiate between red, blue and
green colour. Colour blindness occurs
when any of these cone cells fail to
perform their function.

There are several other factors, which

can cause colour vision problems in
an individual. The factors may
include:

• Damage caused to the brain

or eye or to the nerve cells.
• Genetic disorders and cell
mutations.
• Side effects of drug
addiction.
• Use of narcotics like tobacco and alcohol.

Signs and Symptoms of Colour Blindness

Symptoms of colour-blindness include the following:

• Rapid and continuous eye movement.

• Sensitivity towards bright light.
• Trouble in seeing different colours and the brightness of
any respective colour.

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 • The problem is differentiation between various shades of
the same colour.

Diagnosis of Colour Blindness

ISHIHARA PLATE TEST
The Ishihara colour test is one of the most well-known tests for
diagnosing colour blindness. It involves a series of plates with
coloured dots, and within these dots, numbers or patterns are
hidden. People with normal colour vision can see the numbers or
patterns, while those with colour vision deficiencies may not be
able to distinguish them accurately.

Fig: Ishihara Plate test

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 BIBLIOGRAPHY
On the helm of this, I would like to give my regards to the
following author of books and websites, from which I have taken
help in completing my investigatory project on “Mendelian
Disorders”.

➢ Biology Textbook, NCERT

➢ www.bankofbiology.com
➢ www.wikipedia.com
➢ www.NHLBI (National Heart, Lung, and Blood Institute).com
➢ www.google/images.com

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