in these slides describes types of mutation and their causes.

2. Mutation
Present by;
Naseem bhurgri
Ph.D. scholar ( biotechnology university of Sindh)

3. MUTATION
A mutation is a change in genetic material.
 A mutation is a change in the DNA sequence or chromosomal mutation.
 Most mutation are the result of error during DNA replication process/
error during DNA repair.
 Some types of mutations are known to be caused by certain chemicals
and ionizing radiation, UV

4. mutation

5. Type of mutation
 Types of mutation
 Molecular chromosomal
 Substation
 Insertion
 Deletion
 frameshift
 Inversion
 Duplication
 translocation

6. “
”
Mutation types
Two types of mutation
Spontaneous Mutations
Induced mutations

7. SPONTANEOUS MUTATION
 they are mainly caused during dna replication or by incorporation of
incorrect nucleotide in the growing dna chain .
 They occur naturally by changes in DNA sequence during
replication.

8. induced mutation
are caused by the changes in
DNA brought about by
some environmental factor
called mutagens.
 E.g.- UV light,x-
rays,gamma rays etc…,

9. Types of Mutation on molecular basis
Substitution
•Insertion
•Deletion
•Frameshift

10. Substitution
 A substitution is a mutation
that exchanges one base
for another (i.e., a change
in a single "chemical
letter" such as switching an
A to a G).

11. Insertion
Insertions are mutations in which extra base pairs are inserted into a new place in
the DNA

12. Deletion mutation

13. Frameshift Mutations
a mutation caused by the addition
or deletion of a base pair or base
pairs in the DNA of a gene
resulting in the translation of the
genetic code in an unnatural
reading frame from the position of
the mutation to the end of the
gene

14. EFFECT OF MUTATION ON PROTEIN
FUNCTION

15. “
”
EFFECT OF MUTATION ON
PROTEIN Function
Mutation exert their phenotypic effects by one of the two mechanism.
Loss of function
Gain of function

16. Mutations are also classified by their
impact on protein function
Loss of function
Complete loss of the protein:
E.g null, loss-of-function, amorph
Reduction of protein’s ability to work:
 e.g hypomorph, reduction-of-function

17. Gain of function
Inrcease in the protein’s function:
E.g hypermorph, gain-of-function
A protein that interferes with the wild-type protein’s
function:
E.g antimorph, dominant negative

20. A case study of the effects of mutation:
 Sickle cell anemia Sickle cell anemia is a genetic disease with severe symptoms, including
pain and anemia.
 The disease is caused by a mutated version of the gene that helps make hemoglobin —a
protein that carries oxygen in red blood cells.
 People with two copies of the sickle cell gene have the disease.
 People who carry only one copy of the sickle cell gene do not have the disease, but may
pass the gene on to their children.

21. How Does a Child Get Sickle Cell
DIsease? •
 Sickle cell disease is inherited through genes.
 For a child to have any form of sickling disease, each parent will have an abnormal
hemoglobin. One possibility is that each parent has sickle cell trait (AS).
 Another possibility is when one parent has the disease (SS) and the other parent has sickle
cell trait (AS).
 In hemoglobin SC disease, one parent has sickle cell trait and the other parent has a
different trait (hemoglobin C).
 In sickle beta-thalassemia, one parent has sickle cell trait (or sickle cell anemia) and the
other parent carries the trait for beta thalassemia (or has thalassemia major).

22. How Does a Child Get Sickle Cell
DIsease? •

23.  sickle-cell anemia is caused by a single point mutation
in the nucleotide sequence of β-globin.
 The seventh triplet should read GAG which colds for
glutamic acid, but the middle nucleotide has changed
to a thymine, which changes the triplet to GTG, which
codes for valine.
 Replacement of the normally charged glutamic acid
with the hydrophobic valine
 Replacement of the normally charged glutamic acid
with the hydrophobic valine alters the solubility of
hemoglobin, so that at a lower oxygen concentration,
the altered protein changes the red blood cell to a
sickle shape that is unable to carry oxygen. This
causes the symptoms of sickle-cell anemia.

24. Hemoglobinopathies
 Disorders of the human hemoglobins
 Most common single gene disorders in the world
WHO: 5% of the world’s population are carriers for
clinically significant hemoglobinopatihies
 Well understood at biochemical and molecular levels

25. Hemoglobinopathies?
What are they?
Disorders where the production of normal adult
hemoglobin in partly or completely suppressed
or replaced by a variant hemoglobin.

26. Broad Classification System for
Hemoglobin Disorders
Qualitative:
Characterized by decreased production of hemoglobin resulting from decreased synthesis of one particular
globin chain
Hemoglobins differ in sequence of amino acids composing globin chain
Disorders called hemoglobinopathies
Quantitative:

27. •Thalassemia.
 Thalassemia is an inherited blood disorder in which the body
produces an abnormal form of hemoglobin which results in
excessive destruction of red blood cells and further leads to anemia.

28. Thalassemia
ALPHA
THALASSEMIA BETA
THALASSEMIA

29. Alpha Thalassemia
Alpha Thalassemia Alpha thalassemia is the result
of changes in the genes for the alpha globin
component of hemoglobin.

30. Pathophysiology
 Therefore, alpha thalassemia occurs when there is a disturbance in production of α-globin
from any or all four of the α-globin genes.
 When functional point mutations, frame shift mutations, nonsense mutations, and chain
termination mutations occur within or around the coding sequences of the alpha-globin
gene cluster hemoglobin is impaired
 . When that occurs, protein synthesis may be inhibited.

31. . Pathophysiology
 Normal production of alpha chains is absent which results in excess production of gamma-
globin chains in the fetus and newborn or beta- globin chains in children and adults.
 The β-globin chains are capable of forming soluble tetramers (beta-4, or HbH)
 This form of hemoglobin is still unstable and precipitates within the cell, forming
insoluble inclusions called Heinz bodies
 These Heinz bodies damage the red blood cells.
 This further results in damage to erythrocyte precursors and ineffective erythropoiesis in
the bone marrow, hypochromia and microcytosis of circulating red blood cells

32. Mutated Thalassemia
 Alpha (0) thalassemia – More than 20 mutations have been found
 . Those that result in the functional depletion of both pair of α -globin genes
 Individuals with this disorder are not able to produce any functional α -globin and thus
are unable to make any functional hemoglobin A, F, or A2.
 This leads to the development of hydrops fetalis or hemoglobin Bart (excess buildup of
fluid before birth)

33. Clinical Presentation
Enlarged liver and spleen
Weakness
Pale skin
Shortage of red blood cells- Anemia

34. Clinical Presentation
Abnormalities of
the urinary
system or
genitalia
Abnormal
bleeding
Hb Bart syndrome
can cause
complications in
pregnancy such as
Premature
delivery
High blood
pressure•

35. Treatment of Alpha Thalassemia
 Treatment for thalassemia often involves regular blood transfusions and folate
supplements.•
 If you receive blood transfusions, you should not take iron supplements. Doing so
can cause a high amount of iron to build up in the body, which can be harmful.
 Persons who receive significant numbers of blood transfusions need a treatment
called chelation therapy to remove excess iron from the body.
 Bone marrow transplant may help treat the disease in some patients, especially
children.

36. Medications•
 FOLIC ACID- ORAL•
 FOLIC ACID - INJECTION•
 DEFEROXAMINE - INJECTION

37. BETA THALASSEMIA
 Beta thalassemia is a genetic blood disorder that reduces
the production of hemoglobin.
 Beta Thalassemia• Specifically, it is characterized by a
genetic deficiency in the synthesis of beta- globin chains
 .• Beta-globin is a component (subunit) of hemoglobin.

38. There are 3 types of Beta Thalassemia
Thalassemia Minor
Thalassemia Intermediate
Thalassemia Major or Cooley's Anemia

39. Symptoms of Beta Thalassemia
It is characterize by
severe anemia that can
begin months after
birth
Delays in growth and
development
Paleness
Bone marrow
expansion.
Untreated Beta
Thalassemia major can
lead to child death due
to heart failure

40. Treatment of Beta Thalassemia
 Regular blood transfusion helps prevent severe anemia and allows for more normal growth
and development
 There are various medications that target the production of red blood cells (i.e.
erythropoeitin)

41. “
”
ANEMIA
What is anemia
 Anemia is a condition that develops when your blood lacks enough healthy red blood
cells or hemoglobin.
 ANEMIA is the most common blood condition in the U.S. It affects about 3.5 million Americans.
 Women, young children, and people with chronic diseases are at increased risk of anemia

42. TYPES OF ANEMIA
Iron deficiency anemia.
hemolytic anemia.
Megaloblastic anemia
aplastic anemia.
thalassemmia anemia.
Hemorrhagic anemia
Pernicious anemia

43. .Iron deficiency anaemia
excessive
loss of
iron
Women are
at risk.
For
menstrual
blood and
growing
fetus.

44. 2.Megaloblastic anemia
Red bone marrow
produces abnormal
RBC.
Less intake of
vitamin B 12
CANCER
DRUGS.

45. 3.Pernicious anemia
Inability of stomach to absorb
vitamin B 12 in small intestine

46. 4.Hemorrhagic anemia
Excessive loss of
RBC through
-bleeding
stomach ulcers
menstruation

47. 5.Hemolytic anemia
RBC plasma
membrane ruptures
may be due to
parasites,toxins,antib
odies.

48. 6.Thalassemmia anemia
Less synthesis of hemoglobin.

49. .Aplastic anemia
 destruction of red bone marrow
 ♣ caused by toxins,gamma radiation
. ♣ enzymes needed for blood production.

50. SIGN
SYMPTOMS

51. Irritability
Lack of Concentration
Weakness
Infection
Fatigue
DIFFICULTIES
IN
CONCENTRATE
HAIR LOSS

52. TREATMENT
TREATMENT BLOOD
TRANSFUSION
PARENTAL
ORAL IRON
HUMAN RECOMBINANT
EROTHROPROTEIN
INJECTABLE IRON

53. References
 First Known Heart Attack Associated With Beta- thalassemia Major Reported." Heart Disease
Weekly February 22, 2004: 10.
 Bowden, Vicky R., Susan B. Dickey, and Cindy Smith Greenberg. Children and Their Families:
The continuum of care . Philadelphia: W.B. Saunders Company, 1998.
 "Thalassemias." In Principles and Practice of Medical Genetics , Volume 2, edited by Alan E.H.
Emery, MD, PhD, and David L. Rimoin, MD, PhD. New York: Churchill Livingstone, 1983.
 Thompson, M.W., R. R. McInnus, and H. F. Willard. Thompson and Thompson Genetics in
Medicine , Fifth Edition. Philadelphia: W.B. Saunders Company, 1991.
 Olivieri, N. F. "The Beta Thalassemias." The New England Journal of Medicine 341 (1999): 99-
109.