Lesson 3: Mutation(III)

(c) Base Deletion

It is the removal of a base from a normal gene sequence. Like insertions, these mutations can alter the reading frame of the gene. When a nucleotide base pair is deleted from DNA base sequence of a gene, this causes the whole base sequence (reading frame) to be shifted one place forward. In this frameshift mutation, every single triplet code after the deletion point is altered. 

During transcription, the codons assembled in mRNA after mutation point are also different. This gives rise to the production of a different polypeptide with a primary structure containing an incorrect sequence of amino acid. Deletion or insertion more harmful than substitutions or inversion because it leads to production of non-functional protein or enzyme.

Beta (ß)- Thalassaemia Major (Cooley’s anaemia)

 
What is thalassaemia?

It is a group of inherited genetic disorders that cause defective haemoglobin production. Many types of thalassaemia include alpha and beta thallasaemia. There are 2 types of ß-thalasaemia which are ß-Thalassaemia Major( Cooley’s anaemia)and ß-Thalassaemia Minor.

Causes

It is caused by Lack of ß-polypeptide chains and relative excess of α-polypeptide chains. Α-polypeptide chains form insoluble aggregates that precipitate within erythrocytes. This causes damage to cell membranes and render the destruction of erythrocytes by phagocytes. Erythroblasts in the bone marrow also destroyed with an increased absorption of excessive dietary iron

Sign and symptoms

Most children with Cooley’s anaemia appear healthy at birth but within 1^st 2 year of life they become pale, listless and fussy with poor appetite. They grow slowly and often develop jaundice. Red blood cell also smaller in size. Without treatment, the spleen, liver and heart become enlarged and bones become thin and brittle.

Treatment

The patient needs a frequent blood transfusions and the use of antibiotics. Bone marrow transplant or stem cell gene therapy is also encourageable.

Different Between Frameshift and Non-Frameshift Mutation


Frameshift Mutation

• Causes alteration of the whole sequence (reading frame) of nucleotides bases. Every single triplet genetic codes after mutation point is altered  
• Result in a different DNA strands synthesized during semiconservative replication. An altered mRNA with many different codons is produced during transcription. this leads to formation of an incorrect series of amino acids in polypeptide chain.
• It usually have more severe effects on the phenotypes and sometimes lethal to the organisms.
• Insertion and deletion of nucletides bases is the example but they won't cause a change in the reading frame after mutation point.

Non-frameshift Mutation

• It doeas not cause the alteration of the whole nucleotide base sequence
• only the mutated single code in the DNA and single codon in mRNA are affected. Therefore, only one amino acid is different in the resultant polypeptide that is synthesized.
• If different amino acid is located within the active site of an enzyme or involved in the folding of a particular protein, this would affect functioning of the enzyme or protein
• Examples: Substitution and inversion