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.