Download Gene-and-Chromosome-Mutations

(4) Genes and proteins in health
and disease
Genes and
proteins in
health and
disease
(A)
Structure
and
functions of
proteins
(B)
Gene and
Chromosome
Mutations
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
Mutations
Pic is for
Mrs
McLelland

What is a mutation?
• A random change to an organism’s genetic
material (DNA, genes, chromosomes)
What do mutations result in?
1) Proteins are not expressed (proteins
are not made)
2) The protein that is expressed is not
functioning correctly
This is how genetic disorders are caused.
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
• Frame-shift
Chromosome
Structure Mutations
• Deletion
• Duplication
• Translocation
Substitutions
• There are 3 types of
single-nucleotide
substitutions including:
• missense,
• nonsense and
• splice-site mutations.
Missense mutations
Nonsense mutations
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
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
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
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
TASK:
Copy the table below
Work through each case study and complete your table
Condition
Type of mutation
Sickle cell disease
missense
Phenylketonuria
(PKU)
ß (beta)
thalassemia
Duchenne muscular
dystrophy (DMD)
Tay-Sachs
syndrome
missense
Cystic fibrosis
Huntingdon’s
disease
Fragile X syndrome
Splice-site
mutation
nonsense
Frameshift
insertion
Frameshift
deletion
Nucleotide sequence
repeat expansion
Nucleotide sequence
repeat expansion
Effect on health
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.
Deletion
1
1
2
2
New
3 chromosome
3
7
4
5
6
7
8
Original
chromosome
BREAK
8
4
5 Deleted
genes
6
Cri-du-chat
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.
Duplication
1
1
2
2
3
3
4
4
5
BREAK
3
Duplicated
4
Genes from
5
6
5
7
6
8
Original
chromosome
7
8
New
chromosome
Homologous
chromosome
Translocation
1
1
2
2
Chromosome A
3
3
4
4
5
5
Translocated
genes
21
22
Chromosome B
BREAK
21
22
23
23
24
24
Chronic myeloid leukaemia
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.
Down’s syndrome
Here we can see, there is an extra copy of
chromosome 21. BUT…
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.
Chromosome mutations
Type of
Mutation
Deletion
Duplication
Translocation
Description
Significance
Loss of a segment of a Genes lost
chromosomes
repeat of a segment
Duplicated gene
of a chromosome
could mutate
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.
Chronic myelogenous leukemia is an example of a translocation mutation
__________________________
because part of chromosome 22 attaches to chromosome 9.
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