1. GENE MUTATION |Genetics
Reporter: Jaycris C. Agnes
1
Introduction:
Genetic Code
The genetic code is the set of rules by which information encoded within genetic material
(DNA or mRNA sequences) is translated into proteins (amino acid sequences) by living cells.
Gene Mutation
A gene mutation is defined as an alteration in the sequence of nucleotides in DNA. This change
can affect a single nucleotide pair or larger gene segments of a chromosome. DNA consists of
a polymer of nucleotides joined together. During protein synthesis, DNA is transcribed into RNA
and then translated to produce proteins. Altering nucleotide sequences most often results in
nonfunctioning proteins. Mutations cause changes in the genetic code that lead to genetic
variation and the potential to develop disease.
Gene Mutation

2. GENE MUTATION |Genetics
Reporter: Jaycris C. Agnes
2
Kinds of Gene Mutation
1. Point Mutations
Point mutations are the most common type of gene mutation. Also called a base-pair substitution,
this type of mutation changes a single nucleotide base pair. Point mutations can be categorized
into three types:
Silent Mutation: Although a change in the DNA sequence occurs, this type of mutation does
not change the protein that is to be produced. This is because multiple genetic codons can
encode for the same amino acid. Amino acids are coded for by three nucleotide sets called
codons. For example, the amino acid arginine is coded for by several DNA codons including
CGT, CGC, CGA, and CGG (A = adenine, T = thymine, G = guanine and C = cytosine). If the
DNA sequence CGC is changed to CGA, the amino acid arginine will still be produced.
Missense Mutation: This type of mutation alters the nucleotide sequence so that a different
amino acid is produced. This change alters the resulting protein. The change may not have
much effect on the protein, may be beneficial to protein function, or may be dangerous. Using
our previous example, if the codon for arginine CGC is changed to GGC, the amino acid
glycine will be produced instead of arginine.
Types of Missense Mutation:
o Conservative mutations: Result in an amino acid change. However, the
properties of the amino acid remain the same (e.g., hydrophobic, hydrophilic, etc).
At times, a change to one amino acid in the protein is not detrimental to the
organism as a whole. Most proteins can withstand one or two point mutations
before their functioning changes.
o Non-conservative mutations: Result in an amino acid change that has different
properties than the wild type. The protein may lose its function, which can result
in a disease in the organism. For example, 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. The protein may also exhibit a "gain of function" or become activated, such
is the case with the mutation changing a valine to glutamic acid in the braf gene;
this leads to an activation of the RAF protein which causes unlimited proliferative
signalling in cancer cells. These are both examples of a non-conservative
(missense) mutation.

3. GENE MUTATION |Genetics
Reporter: Jaycris C. Agnes
3
Nonsense Mutation: This type of mutation alters the nucleotide sequence so that a stop
codon is coded for in place of an amino acid. A stop codon signals the end of
the translationprocess and stops protein production. If this process is ended too soon, the
amino acid sequence is cut short and the resulting protein is most always nonfunctional.
In this example, the nucleotide cytosine is replaced by thymine in the DNA code, signaling the cell to
shorten the protein.
2. Frameshift Mutation
This type of mutation occurs when the addition or loss of DNA bases changes a gene’s
reading frame. A reading frame consists of groups of 3 bases that each code for one
amino acid. A frameshift mutation shifts the grouping of these bases and changes the
code for amino acids. The resulting protein is usually nonfunctional. Insertions, deletions,
and duplications can all be frameshift mutations.

4. GENE MUTATION |Genetics
Reporter: Jaycris C. Agnes
4
A frameshift mutation changes the amino acid sequence from the site of the mutation.
3. Repeat expansion
Nucleotide repeats are short DNA sequences that are repeated a number of times in a
row. For example, a trinucleotide repeat is made up of 3-base-pair sequences, and a
tetranucleotide repeat is made up of 4-base-pair sequences. A repeat expansion is a
mutation that increases the number of times that the short DNA sequence is repeated.
This type of mutation can cause the resulting protein to function improperly.
In this example, a repeated trinucleotide sequence (CAG) adds a series of the amino acid glutamine to the
resulting protein.

5. GENE MUTATION |Genetics
Reporter: Jaycris C. Agnes
5
Specific diseases caused by gene mutation
Cystic fibrosis
A defect in the cystic fibrosis transmembrane conductance regulator (CFTR) gene
causes cystic fibrosis (CF). A protein made by this gene controls the movement of the water and
salt in and out of the body's cells. Genes in people with CF incorrectly code proteins. This causes
thick, sticky mucus and very salty sweat.
Cancer
Point mutations in multiple tumor suppressor proteins cause cancer. For instance, point
mutations in Adenomatous Polyposis Coli promote tumorigenesis.
Sickle-cell anemia
Sickle-cell anemia is caused by a point mutation in the β-globin chain of haemoglobin,
causing the hydrophilic amino acid glutamic acid to be replaced with the hydrophobic amino
acid valine at the sixth position.
The β-globin gene is found on the short arm of chromosome 11. The association of two
wild-type α-globin subunits with two mutant β-globin subunits forms haemoglobin S (HbS).
Under low-oxygen conditions (being at high altitude, for example), the absence of a polar amino
acid at position six of the β-globin chain promotes the non-covalent polymerisation (aggregation)
of haemoglobin, which distorts red blood cells into a sickle shape and decreases their elasticity.
Below is a chart depicting the first thirteen amino acids in the normal and abnormal sickle
cell polypeptide chain.
Sequence for Normal Hemoglobin
ATG GTG CAC CTG ACT CCT GAG GAG AAG TCT GCC GTT ACT
START Val His Leu Thr Pro Glu Glu Lys Ser Ala Val Thr
Sequence for Sickle Cell Hemoglobin
ATG GTG CAC CTG ACT CCT GTG GAG AAG TCT GCC GTT ACT
START Val His Leu Thr Pro Val Glu Lys Ser Ala Val Thr