The document provides information about thalassemia, including its types, causes, symptoms, identification tests, and treatment options. It begins with an introduction defining thalassemia as a hemoglobin disorder caused by defective synthesis of one or more globin chains. It then discusses the three main types - alpha thalassemia, beta thalassemia major/intermedia, and thalassemia minor. The document outlines the normal structure and function of hemoglobin, how mutations can disrupt this and cause thalassemia, and resulting organ dysfunctions. It details tests to identify thalassemia and standard treatment methods like blood transfusions, iron chelation therapy, and bone marrow transplants. Bioinformatics tools that

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Cell Biology
Quaid - e - Azam University Islamabad

3. Group Members
• UMM -E- KALSOOM.
• MUNEEBAH NOOR.
• SHAZIA SULTAN.
• HIRA SULAIMAN.

4. Topic
“THALASSEMIA”
Submitted To:
Mam Farya Tanvir

5. Sequence:
• Introduction(1-5).
• Normal Function(6-9).
• Dysfunction(10-13).
• Symptoms &
Identification(14-17).
• Treatment & Cure(18-22).
• Bio info. Applications(23-
29).

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Thalassemia:
Introduction What is Thalassemia?
1930:
From Greek “Thalassa” means “SEA”
because this disease was first known around
the “Mediterranean”.
THALASSEMIA is a group of Haemoglobin
Disorder in which the production of normal
haemoglobin is partly or completely
suppressed as a result of defective synthesis
of one or more globin Chains.
Most common single gene disorder
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Types
:
About types
There are three main types of
thalassemia (and four subtypes):-
Alpha
Thalassemia
Hemoglobin H
Hydropsfetaelis
Beta
thalassemia
major
intermedia
Thalassemia Minor
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Alpha Thalassemia:
Its First Type….
The body can’t make alpha globin.(α globin: 4
gene (Two from each parents)).
1. Haemoglobin H : when a person is
missing three alpha globin genes or
experiences changes in these genes & lead to
bone issue.
2. Hydrops fetalis: Severe form, occurs
before birth . It occur when all four alpha
globin genes are altered or missing. . Most
individuals with this condition are either
stillborn or die shortly after being born.
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Beta Thalassemia:
Second Type….
Occurs when your body can’t produce beta
globin.(β globin : Two Gene (One from each
parents))
1. Thalassemia major (Cooley’s
anaemia) : Most severe form, develops
when beta globin genes are missing.
Symptoms of generally appear before a
child’s second birthday. It requires regular
blood transfusions.
2. Thalassemia intermedia: less severe
form. It develops because of alterations in
both beta globin genes. People with
thalassemia intermedia don’t need blood
transfusions.
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Thalassemia Minor:
Third Type….
• Condition is classified as either alpha or
beta thalassemia minor.
• In alpha minor cases, two genes are missing.
In beta minor, one gene is missing.
• lack of visible symptoms can make
thalassemia minor difficult to detect.
• Gene testing is done in this case.
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Hemoglobin:
Introduction….
• Iron containing biomolecule made up of
heme group and globin present in red blood
cells.
• Makes up 96% of the RBCs' dry content
,35% of the total content.
• Also present in macrophages , retinal
pigment epithelium, hepatocytes, cervical
cells, vaginal epithelial cells.
• Found in many invertebrates, fungi, and
plants.
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Hemoglobin :
It normal structure…. • Made of 4 polypeptide chains:
- 2 alpha, 2 beta chains(3D
globular structure)
• Two chains are bonded non covalently
• Each chain contains:
1.heme group
-synthesized in mitochondria
and cytosol of immature RBCs)
-binding site of oxygen.
2.Globin protein
-cytosol by ribosomes.
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Adult &Fetal Hb:
There difference is….
• Infants:
Hemoglobin F- made up of 2 alpha and
2 gamma chains(later replaced by beta
chains).
• Adult:
Hemoglobin A- 2 alpha , 2 beta.
• Globin production control:
alpha globin genes: chromosome 16
beta globin genes: chromosome 11
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Hemoglobin :
It normal function….
The main function of haemoglobin is:
• To carry oxygen from the lungs to the
body tissues, and to exchange the
oxygen for carbon dioxide, and then carry
the carbon dioxide back to the lungs and
where it is exchanged for oxygen.
• It help to maintain PH in the blood.
• The iron molecule in haemoglobin
helps maintain the normal shape of red
blood cells.
• Main function in the regulation of blood
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Dis Function:
Introduction….
• As we know, thalassemia is caused by
inherited mutations that decrease the
synthesis of haemoglobin
• As HbA is encoded by an identical pair of
alpha globin genes on chromosome 16.
• Two beta chains are encoded by a single
beta globin gene on chromosome 11.
• Mutation in DNA of cells that produces
Haemoglobin.
• Deficient synthesis of beta chain.
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Mutation:
Types are….
Types of mutation in haemoglobin:
Splicing mutation:
These are the most common cause of beta+
Thalassemia. Most of these mutation lie within
introns while a few are located within exons.
Promoter region mutation:
These mutation occur during transcription.
Sometime normal beta-globin is synthesized.
Chain terminator mutation:
It is main cause of beta major. The most
common type creates a new stop codon within
an exon. Block the translation and prevent the
synthesis of beta-globin.
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Cell Dysfunction:
About abnormalities…..
• The susceptibility to infections in
thalassemia arises from a large spectrum of
immunological abnormalities this may be
due to dysfunction of spleen.
• Deleterious effects of imbalanced globin
chain synthesis on erythroid maturation and
red cell survival.
• People with thalassemia are at an increased
risk of developing abnormal blood clots.
• It disturb normal blood cycle.
• Iron overload, due to increased
gastrointestinal absorption and blood
transfusion is the
• major cause of tissue damage, or death
morbidity
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Organ Dysfunction:
About abnormalities….
Bone deformities:
bone marrow expand, bones to widen. abnormal
bone structure, especially in the face and skull
bones thin and brittle, increasing the risk of
broken bones.
Spleen enlargement:(splenomegaly)
Spleen function of fighting infection and
filtration disturb. Severe enlargement of the
spleen may necessitate its removal. it has to work
very hard
Slowed growth rates:
cause a child's growth to slow. Puberty also may
be delayed in children with thalassemia.
Heart problems:
Diseases, such as congestive heart failure and
abnormal heart rhythms, may be associated with
severe thalassemia.
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Symptoms:
They are shown as…. The main signs and symptoms are:
Bone deformities in the face
Fatigue
Slowed growth
Delayed puberty
Shortness of breath
Yellow discoloration of skin (jaundice)
or whites of the eyes
Weakness
Dark urine
Greater susceptibility to infections
Skeletal deformities
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Identification:
Tests are….
Several laboratory tests may be used to help detect
and diagnose thalassemia.
HEAMOGLOBIN ELECTROPHORESIS:
This test separate out the different molecules in the
red blood cells , allowing them to identify the
normal type.
COMPLET BLOOD COUNT(CBC):
The CBC determines the number of red blood cells
and how much hemoglobin is in them . it evaluates
the size and shape of the red blood cells present .
These include the mean corpuscular
volume(MCV),a measurement of size of red blood
cells . a low MCV is often the first indication of
thalassemia.
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Identification:
Tests are….
IRON STUDIES:
These may include : Iron , ferritin , unsaturated
iron binding capacity(UIBC),total iron binding
capacity(TIBC),and percent saturation of
transferrin . These tests are ordered to help
determine whether an iron deficiency is the
cause of a persons anemia.
ERYTHROCYTE PORPHYRIN TEST:
This test may be thalassemia used to
distinguish an unclear beta minor diagnosis
from iron deficiency or lead poisoning .
Individuals with beta thalassemia will have
normal porphyrin levels , but those with the
latter conditions will have evaluated
porphyrin.
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Identification:
Tests are….
BLOOD SMEAR:
It is also called peripheral smear and manual
differential . In this test a laboratory
professional examines a thin layer of blood that
is treated with a special stain , on a slide , under
a microscope. The number and type of cells are
evaluated to see if they are normal and mature .
With thalassemia, the red blood cells often
appear smaller than normal.
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Treatment & Cure:
About treatment……
• Depends upon type and severity of
disease.
• Three standard treatments are used for
moderate to severe forms of
thalassemia.
• These are:
 Blood transfusions
 Iron chelation therapy
 Folic acid supplements
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Blood transfusions:
About treatment……
• Gives healthy RBCs with normal
hemoglobin.
• Procedure takes 1 to 4 hours.
• Repeated transfusions are needed due
to 120 days’ life span of RBCs.
• For beta thalassemia intermedia, need
transfusions on occasion.
• For Cooley's anemia, needs regular
transfusions.
• Perform Splenectomy if requirement
are increasing.
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Iron chelation therapy:
Therapy is….
• Therapy used to remove excess iron
due to regular transfusions as it
causes damage to organs.
• Two medicines are used:
- Deferoxamine (liquid med) given
slowly under skin using pump
overnight. May affect hearing and
vision.
-Deferasirox : a pill taken once daily.
May cause headache, vomiting,
joint pain.
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Bone marrow transplant:
Transplant is….
• Replaces faulty stem cells with
healthy ones from a donor.
• It is the only best cure however, only
small number of people are able to
find donor compatibility.
• Folic acid supplements are
recommended by doctor along with
blood transfusions and iron chelation.
• Folic acid is a vitamin B that helps
building healthy RBCs
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Gene manipulation & Replacement:
About treatment……
• Insert a normal hemoglobin gene in
stem cells of bone marrow.
• Increasing the synthesis of fetal
hemoglobin.
• Developing gene editing technologies
and reprogramming somatic cells for
treating Haemoglobinopathies.
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Thalassemia & Bioinformatics:
They are related as….
Bioinformatics, in its broad sense, involves
application of computer processes to solve
biological problems. A wide range of
computational tools are needed in biology and
medicine . Bioinformatics helps in data
analysis , data computation , diagnosis and
treatment of many disease.
Study of Thalassemia uses many
bioinformatics tool in study of:
1.Prevention
2.Diagnosis
3.Cure & Therapy
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Explanation:
It’s applications are
in….
Prevention:
As Thalassemia is inherited blood disorder ,pass from
parents from offspring through genes . By using
different bio info tools family genetic studies also can
help Prevent the disorder.
Diagnosis:
Bioinformatics helps in the diagnosis of disease in
adults as well as in human embryo. Diagnosis in embryo
involve taking a sample of amniotic fluid or tissue from
the placenta. Tests done on the fluid or tissue can show
whether your baby has thalassemia and how severe it
might be.
Treatment:
Main method for treatment is Hematopoietic stem cell
transplantation . which need donor and recipient Human
leukocyte antigen(HLA) compatibility . The tests to
identify antigen are PHLAT(81%) & OptiType (99%)
which are the applications of bioinformatics.
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Tools of Bioinformatics:
About tools……
For every bioinformatics, tools selected to
complete tasks.
1.FASTA: standard expression for
bioinformatics tool, find a sequence of the
required gene against keywords.
2.Clustal W: for checkup the sequences
similarity. , ClustalW accept FATA file that
contains the normal gene (HBB gene
sequence) and the patient/ parents HBB gene
in order to check the gene’s healthy.
3.BLAST: which performs comparisons
between pairs of sequences, searching for
regions of local similarity to start sequence
analysis.
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Organ on a Chip:
Technique is….
Bioinformatics latest technique which help
in pharmacological studies
Used to check drug absorption, metabolism,
& effectiveness of certain drug.
Allow molecular and functional monitoring.
Used for disease modeling
Procedure:
• Place living human cell in an engineered
micro environment.
• They provide an alternative solution to cell
cultures and animal testing.
• The chip recreate what is happening within
the tissue system in the human body.
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OptiType:
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QUESTIONS?

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Reference:
•Shahin Asadi, S. H. (n.d.). ASSESSMENT OF BETA-GLOBIN GENE
MUTATIONS IN PATIENTS WITH BETA-THALASSEMIA CREATED IN THE
CHAIN, THE POPULATION OF THE CITY OF TABRIZ IN IRAN. WORLD
JOURNAL OF PHARMACY AND PHARMACEUTICAL SCIENCES, 5(02, 343-
362).
•Ablahad, A. A. (n.d.). International Journal of Scientific & Engineering
Research. New Approach for Analysis and Prediction of Genetic Beta-
Thalassemia Mutations Based On Bioinformatics, 4(12, December-2013).
Retrieved from http://www.ijser.org
•Wilkinson, M. (2016, dec 15). Retrieved from
https://www.slideshare.net/MalcolmWilkinson2/organ-on-a-chip-
70175991
•Hafeez Kandhro, S. ,. (2017, aug). PUBMED.gov. Retrieved from NCBI:
https://www.ncbi.nlm.nih.gov/pubmed/28934514
•(2014, dec 09). Retrieved from NIH: https://www.nhlbi.nih.gov/health-
topics/thalassemias
• http://www.chemistry.wustl.edu/~edudev/LabTutorials/Hemoglobin/Me
talComplexinBlood.html
• https://courses.lumenlearning.com/boundless-
biology/chapter/transport-of-gases-in-human-bodily-fluids/
• http://www.hematology.org/Patients/Basics/
• https://www.thoughtco.com/red-blood-cells-373487
• https://www.urmc.rochester.edu/encyclopedia/content.aspx?ContentTy
peID=90&ContentID=P02316

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thank you