Transcript Document 266389

• Name the 4 gene mutations that can occur
• State the effect of gene mutations on amino
acid sequences
Genetic Disorders
Definition;
Genetic disorders are caused
by changes to genes or
chromosomes that result in
the proteins not being
expressed or the proteins
expressed not functioning
correctly.
Examples;
Sickle cell anaemia
Duchenne muscular dystrophy
Tay-Sachs syndrome
Cystic fibrosis
Huntingdons
Fragile X syndrome
Beta thalassemia
PKU
Cri-du-chat syndrome
Chronic myeloid leukaemia
Down’s syndrome
Mutation Types
• Mutation – change in structure/composition of
organisms genome
• If the change in the genotype is in phenotype –
individual is called mutant
• Mutations are random occurrences
(spontaneously) and low frequency (rarely) ROLF!
• Mutagens/ mutagenic agents can artificially
increase the rate of mutations.
• Thus these mutations are called
induced
Chemicals include – mustard gas
Radiation – gamma rays/ X-rays +
UV light
Mutation Types
• Single gene mutations involve the alteration of
a DNA nucleotide sequence;
• Point Mutations
– Substitution (missense, non-sense and splice-site)
– (Inversion)
• Frameshift Mutations
– Insertion
– Deletion
Gene Mutations Video
Gene Mutations
• SINGLE GENE MUTATIONS – involve changes in
one nucleotide
• (deletion, insertion and substitution)
bring about only a minor changes as only 1 nucleotide
(ie one different amino acid); sometimes the organism
is affected only slightly or not at all
• FRAMESHIFT MUTATIONS – (insertion & deletion)
leads to a large portion of the gene’s DNA to be
misread; the protein produced differs from the normal
protein by many amino acids and is usually
dysfunctional
Substitution – replace a base;
Missense
• Single-nucleotide substitutions include:
missense (replacing one amino acid codon
with another).
• Diseases caused by missense;
Sickle-cell disease
PKU
Sickle cell anaemia
• Blood disorder where rbc change shape into
an abnormal, rigid , sickle shape.
• This causes problems such as blocking
blood vessels
• Delayed growth
• Fatigue
• Shorter life
• Infections
• Jaundice
BUT
Protects against malaria
Substitution – replace a base;
Non-sense
• Single-nucleotide substitutions include:
non-sense (replacing one amino acid codon
with a premature stop codon).
• Diseases caused by nonsense;
Duchenne muscular dystrophy DMD
Splice-site mutation
• Do you remember what splicing is?
Splicing ..... Hint .....
DNA
Exon
Intron
Exon
Intron
Transcription
Primary
mRNA
Processing
Mature
mRNA
Translation
Protein
Exon
Splice-site mutation
• Do you remember what splicing is?
• Splicing is the post transcription and pretranslational of mRNA ; removing introns and
exons joined together (primary to mature
mRNA), then using certain exons (alternative
splicing)
• Splicing is controlled by a specific nucleotide
sequence at the splice site on introns which
flank (beside) exons. Mutation occurs here.
Substitution – replace a base;
Splice-site
• Splice-site mutations (creating or destroying the
codons for exon-intron splicing).
• Diseases caused by splice-site
Beta (β) thalassemia
Destroying codon
Creating codon
DNA
Exon 1 Intron
Altered
mRNA
Exon 1
Exon 2 Intron
Exon 2
Exon 3
Exon 3
DNA Exon 1 Intron
Altered
mRNA
Exon 2 Intron
Exon 1
Exon 3
Exon 3
Single Gene (point) mutations • DIGS;
Deletion
Insertion
(Gene mutations)
Substitution
(inversion not in arrangements)
Frameshift;
Insertion & repeat expansion
• Nucleotide insertions or an expansion of a
nucleotide sequence repeat (essentially
insertion of a large number of copies of the
nucleotide sequence).
• Results in extra copies of amino acid/ or fails
to express (silenced)
• Examples of repeat
expansion diseases;
Huntingdon's disease
Fragile X syndrome
• Disease of insertion;
Tay-Sachs syndrome
Tay-Sachs syndome
• Recessive chromosome 15 disease that
affects the nervous system.
• Body lacks hexosaminidase A (protein which
breaks down chemicals in ganglioside, fatty
substance GM2, thus builds up and prevents
nerve functioning)
• Slow development
at 6 month
• Loss of movement/
vision/hearing
• Most die at 5yrs old
Frameshift;
Deletion
• Nucleotide deletion of a nucleotide sequence
is the removal of bases, causing a frame shift
• Examples of diseases;
Cystic Fibrosis

Consequences ??
• So if you tweaked the DNA – what is the
consequence?
So if you tweaked the DNA – what
is the consequence?
•The effect of missense, nonsense, splice-site, frameshift
and nucleotide sequence repeat expansion mutations .......
•On the structure of the protein synthesised, its function and
the effect of this on individuals.
Demonstrate your understanding
1. What are the types of gene mutations?
2. Which types do you think will have the greatest
affect on the organism – explain/justify why.
3. Which mutations are frameshift mutations and
can you explain why?
4. Which type of
mutations are
these;
Summary
Single Gene (Point)
mutations
Point mutations occur at a
single point – substitution.
They are generally not
harmful, most of the protein
remaining unaffected.
Since only one amino acid is
affected, the protein will
probably be functional.
(single nucleotide
polymorphism)
Frameshift mutations
After a deletion or insertion the
open reading frame is moved
one base pair forwards or
backwards.
This is generally harmful since
all the amino acids in the
primary structure of the protein
will have changed from the
mutation onwards.
The protein will probably be
non-functioning.
Mutations are always a negative thing
F
A gene mutation is a change in the genetic code
Gene mutations can result in cancer
T
T
Every characteristic of your body is coded for by one gene
Substitutions can be as harmful as additions
F
Cystic fibrosis is caused by the deletion of 3 bases
T
F
Learning Outcomes
• Explain chromosome structure mutations
• Give some examples of chromosome
mutations
• Compare gene to chromosome mutations
Structure of a chromosome altered!
• These mutations can take the form of a;
• Deletion (loss of a segment of a chromosome)
• Duplication (repeat of a segment of a chromosome)
• Translocation (the rearrangement of chromosomal
material involving two or more chromosomes).
• The substantial changes in chromosome mutations
often make them lethal.
Examples ....
Cri-du-chat syndrome
(deletion of part of the short
arm of chromosome 5)
Chronic myeloid leukemia
(CML) (reciprocal
translocation of a gene
from chromosome 22 fused
with a gene on
chromosome 9)
Examples ....
Familial Down’s
syndrome (in 5% of
cases one parent has
the majority of
chromosome 21
translocated to
chromosome 14)
Conclusion
•
•
•
•
How frequent are mutations? (1)
What is a mutant? (1)
Name 4 mutagenic agents.(4)
Name and describe 2 chromosome
mutations.(4)