DNA changes and repair

P arm of chromosome

short arm

q arm of chromosome

long arm

What is recombination

• exchange of genetic material between a chromosome pair to produce progeny with combination of alleles;

• exchange of maternal and paternal chromosomes leads to hereditary traits;

• increases diversity

When does recombination occur

prophase I in meiosis in ‘crossover’

3 types of recombination errors

1. Deletions / duplications.

2. Translocations.

3. Inversions.

Spontaneous mutations due to…

copying errors during replication

Induced mutations are due to…

exposure to external elements.

Germ line mutations occur in

reproductive cells & mutations are passed on to offspring through gametes & inherited from parents

Somatic mutations acquired in…

• somatic cells (non-reproductive). Not passed on to offspring.

• Environmental factors/errors in cell replication

Inheritance of mutations:

• germ cell mutations are hereditary.

• Somatic cell mutations only affect the individual carrying the mutation.

Hereditary germ cell mutations and where they located:

• chromsome pairs 1-22; autosomal dominant. Autosomal recessive.

• Sex-chromosone pair; X-linked dominant. X-linked recessive. Y-linked.

• Mitochondrial.

Locus

location of particular gene on chromosome

Point mutations:

substitution: transition A<->G. C<->T.

Transversion A&C. G&T. A&T. G&C.

3 effects of point mutation

1. Nonsense mutation = changes in DNA sequence creating stop codon.

2. Missense mutation = changes in DNA sequence causes change in a.a. ->effect depends on a.a.

3. silent mutation = change in DNA sequence doesn’t result in change of a.a. -> genetic code is degenerate.

Additions or losses of nucleotide pairs in DNA sequence is called… and results in…

insertion and deletion… frameshift mutation.

Frameshift mutations result in…

• large no. of altered a.a.

• no sense to message.

• Altered resulting protein or no protein.

Duchenne muscular dystrophy

• eg. Nonsense mutation in dystrophin gene.

• Deletions / duplications / frameshifts.

• Mutation results in little/no production of functional protein.

• Dystrophin is vital protein for maintaining muscle strength.

Sickle cell anaemia.

• Eg. Missense mutation.

• Caused by mutation in haemoglobin gene beta on chromosome 11.

• Glu->val.

Tay-Sachs Disease

eg. Frameshift mutation.

• 4 bp insertion into HEXA gene on chromosome 15.

• Codes for enzyme hexosaminidase which breaks down gangliosides.

• Build up of gangliosides in neurones and lysosomes.

• Deterioration of mental and physical abilities.

• Temperature-sensitive mutations:

Himalayan gene

• encodes for tyrosinase.

• Controls production of melanin.

• Temperature sensitive mutation (doesn’t function at 37’).

• Body temp so tyrosinase is inactive and less melanin is produced.

• But extremities allow more melanin to be produced bc tyrosinase functions normally.

Causes of induced mutation

• radiation: UV & X-rays;

• Chemicals: carcinogens & processed foods & cosmetics/cleaning products;

• infectious agents: viruses & bacterium.

Induced damage to DNA causes:

• single-strand break or double strand break;

• damaged base;

• intra-strand crosslink;

• mis-match.

3 processes for correcting DNA damage

1. Proofreading.

2. Mismatch repair.

3. Excision repair.

What is proofreading

• a function that DNA polymerases have that allow them to check correct nucleotide is added during replication.

• 3’-5’ exonuclease activity.

• Detects incorrect nucleotide and removes and replaces immediately.

What is mismatch repair?

• mismatched nucleotides are removed by nucleases (they cut out damaged DNA region).

• After new DNA molecule is synthesised.

• nucleotides replaced by DNA polymerase.

• DNA ligase seals the gaps.

What is nucleotide excision repair?

• after new DNA molecule is synthesised.

• Removes and replaces damaged nucleotides.

• Helices opens helix to form ‘bubble’.

• Nucleases cut out damaged region.

• DNA polymerase replaces missing DNA.

• DNA ligase seals gaps in DNA backbone.

Himalayan gene experiment

icepack on bunnies back with gene.

They have brown match on ears nose feet tail and now back.