MUTATIONS:

What are mutations?

Sudden, heritable changes in the genetic material i.e., an alteration of DNA sequence, any base pair change in any part of a DNA molecule is mutation. It may comprise a single base pair substitution, deletion, insertion or major alteration in the structure of chromosomes. It may occur within a protein coding regions of a gene or within the introns and regulatory sequences. It may occur within germ line cells or in somatic cells. Mutations is the ultimate source of all genetic variation; it provides the raw material for evolution.

Missense mutation: 

A change in one nucleotide of a triplet within a protein coding region of a gene may result in the creation of a new triplet that codes for a different amino acid in the protein product. If this occurs, mutation is known as Missense mutation. It is a non-synonymous substitution and a point mutation. For e.g., sickle cell disease is caused by a single point mutation (a missense mutation) in the beta-hemoglobin gene that converts a GAG codon into GUG which encodes the amino acid valine rather than glutamic acid.

Non-sense mutation:

Mutation in which a triplet or sense codon that corresponds to one of the twenty amino acids specified by the genetic code is changed into a stop codon resulting in the termination of translation of the protein, this is known as nonsense mutation. It usually results out in a non-functional protein product. Some genetic disorders such as thalassemia and DMD result from nonsense mutation.

Frameshift mutation:

A mutation caused by the addition and deletion of a base pair in the DNA of a gene resulting in the translation of the genetic code in an unnatural reading frame. It cause subsequent codons to be changed these are called frameshift mutation because the frame of triplet leading during translation is altered. For e.g., 1) Crohn's disease- insertion of cytosine at position 3020, leads to a premature stop codon, shortening the protein that is supposed to be transcribed. 2) Tay-Sachs disease 3) Cystic fibrosis caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. There are two frameshift mutations in exon 7, one caused by a two-nucleotide insertion, CF1154insTC and the other caused by one-nucleotide deletion CF1213delT. These shifts are predicted to introduce UAA termination codons at residues 369 and 368.

Transition:

A transition is a point mutation that changes a purine nucleotide to another purine (A-G) or a pyrimidine to another pyrimidine (C-T). Transitions can be caused by oxidative deamination and tautomerization. Approximately, two out of three single nucleotide polymorphism (SNPs) are transitions.

Transversion:

Base pair substitutions involving the substitution of a purine for a pyrimidine and vice versa are called transversions. It can only be reversed by a spontaneous reversion. It is less common than transition. This type of mutation is more likely to cause amino acid sequence changes. Transversions are caused by ionizing radiations, strong chemicals.

Photoreactivation:

It is one of the three different mechanisms for the repair of DNA containing thymine dimers. in E.coli. Photoreactivation involves an enzyme that splits thymine dimers directly without the removal of any nucleotide. This enzyme will bind to thymine dimers in DNA in the dark, but it cannot catalyze cleavage of the bonds joining the thymine molecules without energy derived from visible light. The enzyme is also active on cytosine dimers and cytosine-thymine dimers. Thus, when ultraviolet light is used as an experimental mutagen, the treatment is usually carried out in the dark to maximize the mutation frequency.