1. (4) Genes and proteins in health and disease
(A) Structure and functions of proteins
(B)
Gene and Chromosome Mutations

2. Genes and proteins in health and disease (b)
State what genetic disorders are caused by
State what is meant by a mutation
Explain 2 effects mutations have on protein expression
Name the 2 major groups of mutations
Identify single gene mutations
State and describe 5 examples of single gene mutations
Identify chromosome mutations
State and describe 3 examples of chromosome mutations

3. Pic is for Mrs McLelland
Mutations
What effect do mutations in the DNA have?
What is a mutation?
What is a GENE mutation?
Can you name some mutations?
What is a chromosome mutation?
What is a mutagenic agent?
How often do mutations occur?
Can you name examples of mutagenic agents?
Pic is for Mrs McLelland

4. What do mutations result in?
What is a mutation?
A random change to an organism’s genetic material (DNA, genes, chromosomes)
What do mutations result in?
Proteins are not expressed (proteins are not made)
The protein that is expressed is not functioning correctly
This is how genetic disorders are caused.

5. Chromosome Structure Mutations Deletion Duplication Translocation
Key Area 4b - Mutations
Single Gene Mutations
(involves the alteration of a DNA nucleotide sequence) as a result of:
Substitution
Missense
Nonsense
Splice-site
Insertion
Frame-shift
Expansion of a nucleotide sequence repeat.
Deletion
Chromosome Structure Mutations
Deletion
Duplication
Translocation

6. Substitutions
There are 3 types of single-nucleotide substitutions including:
missense,
nonsense and
splice-site mutations.

7. Missense mutations

8. Nonsense mutations

10. Splice-site mutations
Remember: - before mRNA leaves the nucleus it is spliced
Splicing is controlled by specific nucleotide sequences at splice sites on the introns
If a mutation occurs at one of these splice sites, the codon may be affected and the intron will remain attached to the mRNA

11. Single-nucleotide substitutions
Missense: replacing one amino acid codon with another
this results in the protein having one different amino acid
Nonsense: replacing an amino acid codon with a premature stop codon — no amino acid is made and the process stops
This results in the process stopping and a shorter protein is formed
Splice-site mutations: creating or destroying the codons for exon-intron splicing
This results in the mRNA being translated into an altered protein that does not work

12. Some mutations are more serious than others…
Substitution mutations (missense, nonsense) are called POINT mutations
The mutation only occurs at ONE point
They only affect ONE amino acid
Insertion and Deletion mutations are called FRAMESHIFT mutations
ALL amino acids AFTER the initial mutation are affected since the reading frame of 3 bases has shifted
The mutation impacts the rest of the codons and therefore the rest of the amino acid sequence

13. Nucleotide sequence repeat expansion
Clue is in the name! Repeat
The proteins produced will be defective because it contains a string of extra copies of an amino acid
Sometimes, such expansion of a nucleotide sequence repeat can cause a gene to be silenced and not express any protein at all

14. TASK: missense missense nonsense Splice-site mutation
Copy the table below
Work through each case study and complete your table
Condition
Type of mutation
Effect on health
Sickle cell disease
Phenylketonuria (PKU)
ß (beta) thalassemia
Duchenne muscular dystrophy (DMD)
Tay-Sachs syndrome
Cystic fibrosis
Huntingdon’s disease
Fragile X syndrome
missense
missense
Splice-site mutation
nonsense
Frameshift insertion
Frameshift deletion
Nucleotide sequence repeat expansion
Nucleotide sequence repeat expansion

16. Chromosome structure mutations
Chromosome mutations are normally large changes which are usually detectable under the microscope during cell division.
They usually occur during crossing over when the number or sequence of genes may be altered.
When a chromosome is broken it has a sticky end which can join onto other chromosomes.
Therefore, the structure of a chromosome can be altered. These mutations can take the form of a deletion, duplication or a translocation.
If there are substantial changes in chromosome mutations, then these often make them lethal.

17. Deletion 1 1 2 2 3 3 7 4 New chromosome 8 5 6 7 8 BREAK 4 5 6
Original chromosome 4 5 6
Deleted genes

18. Cri-du-chat

19. The chromosomal deletion usually occurs as a random event during the formation of reproductive cells (eggs or sperm) or in early foetal development. People with cri du chat typically have no history of the condition in their family.
Cri-du-chat
The clinical symptoms of cri du chat syndrome usually include a high-pitched cat-like cry, mental disturbance, delayed development, distinctive facial features, small head size, widely-spaced eyes, low birth weight and weak muscle tone in infancy.

20. Duplication 1 2 1 3 2 4 3 4 5 5 6 6 Duplicated 7 7 Genes from 8
New chromosome 1 2 3 4 5 6 7 8
Duplicated
Genes from
Homologous
chromosome 1 2 3 4 5 6 7 8
BREAK
Original chromosome

21. Translocation 1 1 2 2 3 3 4 4 5 5 21 Chromosome A 2223 24 1 2 3 4 5 21 22
Translocated genes 1 2 3 4 5 21 22 23 24
Chromosome A
Chromosome B
BREAK

22. Chronic myeloid leukaemia

23. Chronic myelogenous leukemia
Chronic myelogenous leukemia (CML) is a slow-growing bone marrow cancer resulting in too many white blood cells. CML is a relatively common form of leukaemia, but overall it is a relatively uncommon type of cancer.

24. Down’s syndrome
Here we can see, there is an extra copy of chromosome 21. BUT…

25. Familial Down’s syndrome
In 5% of cases, the additional chromosome 21 can appear because the majority of chromosome 21 is translocated to chromosome 14.

26. Chromosome mutations Type of Mutation Description Significance
Deletion
Loss of a segment of a chromosomes
Genes lost
Duplication
repeat of a segment of a chromosome
Duplicated gene could mutate
Translocation
the rearrangement of chromosomal material involving two or more chromosomes
Problems of homologous pairing during mitosis or meiosis.
Cri-du-chat
____________________ is an example of a deletion mutation because part of chromosome 5 has been deleted.
__________________________ is an example of a translocation mutation because part of chromosome 22 attaches to chromosome 9.
Chronic myelogenous leukemia

27. Genes and proteins in health and disease (b)
State what genetic disorders are caused by
State what is meant by a mutation
Explain 2 effects mutations have on protein expression
Name the 2 major groups of mutations
Identify single gene mutations
State and describe 5 examples of single gene mutations
Identify chromosome mutations
State and describe 3 examples of chromosome mutations