Mutations. The picture shows a human genome Karyotype. Look at it carefully and discuss.
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Transcript of Mutations. The picture shows a human genome Karyotype. Look at it carefully and discuss.
Mutations
• The picture shows a human genome Karyotype.
• Look at it carefully and discuss.
What I need to know:-
1. That genetic disorders are caused by changes to genes or chromosome
2. This results in proteins not being expressed or the protein expressed not functioning correctly
3. Mutations are rare and can be artificially increased by mutagenic agents
4. Single gene mutations is the alteration of a DNA nucleotide (insertion, deletion and substitution)
5. Single nucleotide substitutions can be missense, nonsense or splice site.
6. Chromosomes can be altered by deletion, duplication or translocation.
• A mutation is a change in the structure or amount of genetic material in an organism. • It can vary from tiny changes in DNA structure of gene
level to large scale alterations in chromosome structure or number.
• When such a change in genotype produces a change in phenotype the individual affected is a called a MUTANT
Frequency of Mutation
• Naturally occurring mutations are very rare. They occur spontaneously and randomly. • Most are recessive so don’t show in the phenotype for
several generations. For it to show in the first generation it must be dominant or sex linked.
• A mutation rate is worked out as the number of mutations at the gene locus per million• This can vary from gene to gene and species to species
Mutagenic Agents
• Usually chemical which ARTIFICIALLY increase the chances of bringing about a mutation
• Eg, Chemicals ( mustard gas, lead oxide)• Radiation ( gamma rays, x-rays, UV lights)
Genetic Disorder
• A condition or disease that can be shown to be directly related to a individual’s genotype is called a genetic disorder.
• A change in the gene caused by a mutation will result in either no protein being made or a faulty protein being expressed.
• Some mutations may be harmful (lethal) as essential proteins (in metabolic pathways for example) are not being processed properly.
Gene mutations
• Single gene mutation – involves an alteration of a nucleotide sequence in the gene’s DNA
• Point mutations – involves a change in one nucleotide in the DNA sequence of a single gene. Types of point mutations include substitution; insertion and deletion
Substitution – only one amino acid changed
G U A
Valine
DNA
mRNA
Amino acid
C T T
G A A
Glutamic acid
Normal
C A T
Mutant
Insertion – all amino acids altered (frameshift)
A G A G T C DNA
mRNA
Amino acid
Normal
U C U C A G
Serine Glutamine Proline
A G A G G T C
Mutant
U C U C C A G
Serine
Deletion – all amino acids altered (frameshift)
A G A G C T
Mutant
U C U C A G A
DNA
mRNA
Amino acid
Normal
A G A G T C T
Serine Glutamine
U C U C G A
Serine Alanine
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
• A gene mutation can also be the result of a trinucleotide repeat expansion• This can result in the production of a defective protein
possessing a string of extra copies of a particular amino acid which may silence the gene and it fails to express any protein
Impact on protein structure
Missense• Following a substitution, the altered codon codes for an
amino acid that still makes sense but not the original sense
Nonsense• As a result of a substitution, a codon that used to code
for an amino acids is exchanged for one that acts as a stop codon. It causes protein synthesis to be halted prematurely and results in the formation of a polypeptide chain that is shorter than normal and unable to function.
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.• As the change can be substantial the mutation is
harmful• There are several ways this can happen:
Chromosome mutations
Type of Mutation
Description Significance
Deletion Genes chopped out
Genes lost
Duplication Genes copied twice
Duplicated gene could mutate
Translocation
Genes stick to different
chromosomes
Problems of homologous
pairing.
Deletion1
2
3
7
8
New chromosome
1
2
3
4
5
6
7
8
BREAK
Original chromosome
4
5
6
Deleted genes
Duplication1
2
3
4
5
6
7
8
BREAK
Original chromosome
New chromosome
1
2
3
4
3
4
5
5
6
7
8
Duplicated
Genes from
Homologous
chromosome
Translocation
23
24
1
2
3
4
5
21
22
Translocated genes
1
2
3
4
5
21
22
23
24
Chromosome A
Chromosome BBREAK
Case studies
• There are many genetic disorders that arise from single gene and chromosome mutations.
Glossary• CHROMOSOMAL MUTATION - a type of mutation involving
alteration(s) in chromosome structure. Examples include deletion, duplication and translocation.• DELETION MUTATION - a gene mutation in which a base or
part of a chromosome is removed.• INSERTION MUTATION – a gene mutation in which one or
more bases are added to a gene sequence.•MISSENSE - A form of point mutation resulting in a codon
that codes for a different amino acid than originally planned for.
•MUTAGENIC AGENT – a factor which causes mutations to occur, e.g. a chemical or certain forms of radiation.•MUTATION – an unplanned, random change to the genetic code
which can be harmful.• NONSENSE - A form of point mutation resulting in a nonsense
codon that does not code for an amino acid and leads to a protein product that is cut short.• SPLICE SITE MUTATION - a gene mutation that results in an
intron being retained by modified mRNA which could result in an altered protein which may not function properly.• SUBSTITUTION MUTATION – a gene mutation in which one base
is substituted by another.