Lesson objectives

• Discuss the genetic basis of disease in

terms of altered base sequence, causing
alterations in protein structure and
function
 Success criteria
• Explain the changes of the bases in the
DNA structure
• Explain the genetic basis of diseases
such as cystic fibrosis, sickle cell
anaemia and haemophilia
 Keywords
• Mutation
• Deletion
• Substitution
• Insertion
• Point
• Frameshift
 Mutations
• Mutation is a change in genetic material/
miscopied DNA/ deleted DNA
A mutation can be inherited, caused by
environmental agents, or happen
spontaneously
Mutagen – anything environmental that can
cause a change in DNA
• Types of gene Mutations:
Gene mutations – deletion
Gene mutations – insertion (frameshift)
Gene mutations - substitution
Gene mutations - substitution
 Silent mutation

• A silent mutation alters DNA sequence, but

has no apparent detectable effect on a
phenotype or a function.
• The amino acid sequence is not changed
because of the change in base so a normal
functioning protein is produced.
 CAC-GTG-GAC-TGA-GGA-CTC-CTC
mRNA GUG-CAC-CUG-ACU-CCU-GAG-GAG

Val-His-Leu-Thr-Pro-Glu-glu

Replacing C at position 18 with T

CAC-GTG-GAC-TGA-GGA-CTT-TTC

mRNA GUG-CAC-CUG-ACU-CCU-GAA-GAG

Val-His-Leu-Thr-Pro-Glu-Glu
 – substitution, insertion, and deletions of bases
are examples of point mutation because they
occur at a single point
– May only change one amino acid coded for.
E.g
CACGTGGACTGAGGACTCCTC
Give the amino acids that code for this DNA
mRNA GUGCACCUGACUCCUGAGGAG
AMINO ACID SEQUENCE
Val-His-Leu-Thr-Pro-Glu-glu
• Change the T at position 17 to A and give
the new amino acid sequence.
CACGTGGACTGAGGACACCTC
mRNA GUGCACCUGACUCCUGAGGAG

CACGTGGACTGAGGACTCCTC
Codon for CTC = glutamate

CACGTGGACTGAGGACACCTC
Codon for CAC =valine
glutamate

valine
 Effects of the changes
• The pH of that area of the protein would change
• Protein becomes less hydrophilic / soluble or
more hydrophobic
• Fewer hydrogen bonds or more van der Waals’
(id–id) forces
• Fewer ionic bonds form
• The tertiary structure/ folding/(3D) shape (of the
protein) would change
• the active site would be different/ less efficient
 Sickle Cell Anemia

• Caused by point mutation e.g change from

glu-Val
• Mutation in blood protein
• “sickle” shape to RBC
• Screening tests
• Pain associated with blocked vessels, causes
anemia (fatigue)
 Substitution
• TACATATGCGGAGGTACT
• Give the amino acids that code for this DNA
mRNA-AUGUAUACGCCUCCAUGA
Amino acid sequence-
Met-Tyr-ser-pro-gln-stop
Change the A at position 6 to T
TACATATGCGGAGGTACT
TACATTTGCGGAGGTACT
Met-stop
Effects -Haemophilia
• Caused by introduction of a stop
codon that reduces the protein
chain hence affects its function.
• Failure of blood to clot
• Rare in females
• Injections with clotting factors to
stop bleeding episodes
 Frameshift Mutation:
• When codons get changed because of
additions or deletions that type of mutation
is called frameshift
– Changes the combinations so that different
amino acids are coded for. E.g

In the DNA base sequence below

-TAT TAG AAG CCT CAG TCA-
Ile-Ile-Phe-Gly-Val-Ser-
Removing AGG from the sequence removes
Phe.
 Effects of the changes
• Protein becomes less hydrophobic
• Fewer van der Waals’ (id–id) forces
• The tertiary structure/ folding/(3D) shape (of
the protein) would change
• the active site would be different/ less
efficient
• Example of disease caused by this- Cystis
fibrosis
 Cystic Fibrosis (CF)
• Caused by deletion of bases from the DNA structure that
causes the amino acid sequence to be affected.
• Recessive disorder
• Mutation stops production of protein in lung cells,
pancreas
• Thick mucus, bacterial infections in lung
• “sweat test”
• Chest percussions, diet supplements
• Shortened life expectancy
 Effects of the changes
• Protein becomes less hydrophobic
• Fewer van der Waals’ (id–id) forces
• The tertiary structure/ folding/(3D) shape (of
the protein) would change
• the active site would be different/ less
efficient