MUTATIONS
Definition:
Mutation is a change in a gene or chromosome. It is a rare, random change in the
genetic material, and in some cases it can be inherited.
Causes of mutation. Mutation can be spontaneous. It just happens, or it can
happen because of: ionising radiation, chemical mutagens – such as tar from
cigarette smoke.
Exogenous causes of mutations -ionization radiation, ultraviolet radiation, alkylating
agents (mustard gas), polycyclic aromatic hydrocarbons (found in tobacco smoke,
charred food, combustion products), crosslinking agents (cyclophosphamide),
insertional mutagenesis (integration of viral genome), and other toxins.
If a mutation involves a change in a single nucleotide base pair, this is referred to
as a point mutation. However, it is important to understand that proteins are coded for
in groups of 3 nucleotides, termed codons. Each codon contains instructions to create
exactly one amino acid, which is then added to the growing protein chain during
translation. Point mutations have different consequences depending on which codon
and what part of it they affect
Silent mutations can occur when a point mutation occurs in non-coding or non-
regulatory regions of DNA, sparing genes and codons. Much of the human genome
is neither used for genes or genetic regulation, with only about 8% used for biological
activity. As a result, any mutation in the non-biologically active regions would be silent.
Silent mutations may also occur even if a mutation targets a codon, and this is due to
redundancy in the genetic code, also referred to as degeneracy
A mutation within a codon result in it coding for a different amino acid, this is
termed a missense or substitution mutation. In effect, one amino acid was replaced
with another. For example, if the CGU that codes for arginine were changed to CAU,
this would result in the placement of a histidine instead of arginine, thereby changing
the amino acid composition of the protein. Sickle cell disease and certain forms of ALS
are examples of pathology caused by nonsynonymous substitution missense
mutations.[
Nonsense mutations occur when a single nucleotide change results in a stop
codon (UGA, UAA, UAG), resulting in premature termination of protein translation. The
majority of cases of beta-thalassemia, for example, are caused by a variety of nonsense
mutations with varying degrees of severity
Frameshift mutations, in contrast, result from either the insertion of a new
nucleotide into the DNA strand or the deletion of a pre-existing nucleotide. This can
occur through transposons, toxins, mutagens, or viruses. The human papillomavirus
(HPV), for example, relies on the insertion of its genetic material into the host’s genome
for its life cycle to progress successfully.[
Frameshift mutations are notable due to their implication in the pathogenesis of
various cancers, particularly prostate and colorectal cancer
In summary
A point mutation is defined as change in a single nucleotide.
Defective gene produces an abnormal protein.
This may be subclassified as
(a) substitution;
(b) deletion and
(c) insertion.
A point mutation may change the codon for one amino acid to a synonym for the same
amino acid.
(d) Then the mutation is silent and has no effect on the phenotype.
(e) For example, CUA is mutated to CUC; both code for leucine, and so this
mutation has no effect
i) Large gene deletions,
(f) e.g., alpha thalassemia (entire gene) or hemophilia (partial)
ii) Deletion of a codon,
(g) e.g., cystic fibrosis; one amino acid is missing in the CFTR protein.
iii) Deletion of a single base, which will give rise to frameshift effect.
i) Single base additions, leading to frameshift effect.
ii) Trinucleotide expansions. In Huntington's chorea, CAG trinucleotides are repeated
30 to 300 times. This leads to a polyglutamine repeat in the protein.
iii) Duplications. In Duchenne Muscular Dystrophy (DMD) gene is duplicated in the
disease.
Ames Test
Mutations
Mutations
Base Substitution Frame Shift
Silent Missense Nonsense Deletion insertion
Gene mutation
Cysteine - UGA UGC UGA- non sense
UAU- Missense- tyrosine
Chromosomal mutation
1.Chromosomal deletion- in Chromosome No.5
Chi du chat ( cry of the cat)
2.Duplication- chromosome 22- an segment is inserted
Charcot Marie tooth Diseasse
Peripheral myelin protein PMP 22
3.Inversion
A segment of the chromosome is removed and inserted again opposite to its original orientation
X-gene F13clotting Facotr VIII- Hemophilia
4.Translocation
Pat of the chromosome chromosome 22 to chromosome 9
Chronic myelogenesis leukemia
