L7: DNA mutations

Question 1

What is the definition of DNA mutation?

Answer 1

It is a permanent change of base sequence of nucleotides in the genetic code

Question 2

What are the types of DNA mutation?

Answer 2

It may be:- gross at the level of the chromosome,
- small at DNA level.
- Germinal occurring in germ cells and can be passed on to future generations
- Somatic occurring in somatic cells and cannot be transmitted to offspring.

Question 3

What is the effect of DNA mutation?

Answer 3

❖ Once the gene has been mutated or changed, the mRNA transcribed from that gene will now carry an altered message.

❖ The resulting polypeptide will now contain a different sequence of amino acids.

❖ Then, the function of the protein made by folding this polypeptide will probably be changed or lost.

Question 4

What are the (classes) causes of mutations?

Answer 4

1) Spontaneous mutations (molecular decay)

2) Induced mutations caused by mutagens

Question 5

What is Spontaneous mutations (molecular decay)?

Answer 5

Mistakes happen spontaneously during DNA replication or repair

Question 6

What is Induced mutations caused by mutagens?

Answer 6

Induced Mutations occur when cells are exposed to external mutagens.

Question 7

What are the types of mutagens?

Answer 7

physical, chemical and biological

Question 8

What are the physical mutagens?

Answer 8

❖ Ionizing radiation (gamma and X-rays)

❖ Non-ionizing radiation:- Ultraviolet radiation- Electromagnetic radiation (Mobile phone, satellite, computer)

Question 9

What are chemical mutagens?

Answer 9

❖ Cigarette smoke

❖ Free radicals and oxidizing agents

❖ Aflatoxin (leading to liver cancer)

❖ Heterocyclic amines (found in over-cooked food)

❖ some of Chemotherapy and antibiotic drugs.

Question 10

What are biological mutagens?

Answer 10

❖ Hepatitis C virus (HCV) → Hepatocellular carcinoma

❖ Human papilloma virus (HPV) → cancer cervix

❖ Human Herpes virus (HHV) → sarcoma

❖ H pylori → cancer stomach

Question 11

What is the classification of mutations?

Answer 11

1)Structural classification (according to structural change in the DNA)

2)Functional Classification

Question 12

What is the structural classification of mutations?

Answer 12

Question 13

What is the functional classification of mutations?

Answer 13

❖ Small scale Mutation (1-20 base mutation):
1- Point Mutations (Base substitution)
2- Frame shift mutations
3- Splicing Mutation
4- Regulatory Mutation

❖ Large scale Mutation (ranged from Exon to whole gene):
1- Transolcations
2- Inversion
3- Duplication
4- large deletion

Question 14

What are the types of point mutations?

Answer 14

Question 15

What causes frameshift mutations?

Answer 15

it is due to additions or deletions of one or more nucleotides lead to alter the reading frame (reading sequence) and the resulting amino acid sequence may become completely different from the wild type

Question 16

What causes Splicing mutation?

Answer 16

it is due to alteration of exon-intron junction sequences, which interfere with mRNA splicing which may lead to the production of abnormal proteins.

Question 17

describe regulatory mutation

Answer 17

❖ it is a mutation in regulatory element which lead to abnormal level of gene expression

❖ It ranges from abnormal high expression level to no expression level

Question 18

Describe translocations “DNA mutations”

Answer 18

large DNA segment moves to new location.

Question 19

Describe inversion “DNA Mutation”

Answer 19

Orientation of DNA segment reverses.

Question 20

Describe duplication “DNA mutation”

Answer 20

Repetition of a portion of a chromosome.

Question 21

What are the clinical applications for mutation?

Answer 21

1) Diagnosis of genetic diseases
2) Carrier detection.
3) Prenatal diagnosis
4) prognosis of some diseases
5) Gene therapy

Question 22

What is molecular hematology?

Answer 22

It is the study of the molecular basis of benign (e.g anemia) and malignant (e.g leukemia) hematological disorders.

Question 23

What is the best example for point mutation?

Answer 23

Benign disorders e.g hemoglobinopathies are the best example for point mutation

Question 24

What are hemoglobinopathies ?

Answer 24

It is a group of disease related to abnormal hemoglobin synthesis e.g:
1) Sickle cell Disease (SCD)
2) Beta thalassemia.
3) Alpha thalassemia.

Question 25

What is the nature of sickle cell disease (SCD)?

Answer 25

It is an autosomal recessive disease

Question 26

What characterizes sickle cell disease?

Answer 26

• Chronic hemolytic anemia
• Presence of abnormal insoluble hemoglobin S (Hb S)
• Presence of a missense point mutation in the codon 6 of beta globin gene (GAG→GTG), changing the 6th amino acid of the beta chains from glutamic acid to valine (Glu 6 Val)
• This leads to polymerization of hemoglobin and distortion of the red blood cells into a sickle shape.

Question 27

What are other names for Beta Thalassemia?

Answer 27

Cooley’s Anemia, Mediterranean Anemia

Question 28

What characterizes Beta Thalassemia?

Answer 28

β-thalassemia is characterized by reduced synthesis of the hemoglobin beta chain that results in:
- microcytic hypochromic anemia,
- reduced amounts of hemoglobin A (HbA)
- increase amount of HB A2 and HB F

Question 29

What causes β-thalassemia?

Answer 29

The β-thalassemia can be caused by more than 200 different gene mutations on chromosome 11.

Question 30

What types of mutation do β-thalassemia mutations include?

Answer 30

all types of mutation (point mutation, frame shift, regulatory, splicing, or even large deletion)One patient may have one or more of these mutations.

Question 31

What is the nature of α- thalassemia?

Answer 31

❖ It is an autosomal recessive disease

Question 32

What is the result of α- thalassemia?

Answer 32

❖ result in decreased alpha-globin production resulting in an excess of β chains in adults.

❖ The excess β chains form unstable tetramers (called Hemoglobin H or HbH of 4 beta chains) which have abnormal oxygen dissociation curves

Question 33

What causes α- thalassemia?

Answer 33

It results from a large (exon or gene) deletion mutation in α1-globingene on chromosome 16