1. Mutations
Year 11

2. Mutations
A mutation is a permanent genetic mistake in a gene or a chromosome.
Mutations can occur spontaneously or be induced. Spontaneous mutations arise from errors in replication. Induced mutations are caused by mutagens.
Mutations are the only way that new alleles can be created

3. Mutagens
Mutagens are chemicals or radiation that can induce mutations eg. Nuclear radiation, UV rays, x-rays, tobacco, agent orange, asbestos.

5. The effect of mutations
When mutations occur in the testes and ovaries they will be inherited by future generations (GAMETIC MUTATIONS).
Somatic mutations in body cells are not inherited but can effect the person during their life time.

7. Not all mutations are bad
Beneficial mutations:
Examples: 1) bacteria becoming resistant to antibiotics
2) pesticide resistance
3) tolerance to high cholesterol levels (see page 143)
4) fast rates of mutations in the protein coat of viruses

8. Harmful mutations
Cystic fibrosis
Sickle cell disease
Albinism

9. Neutral mutations
Are neither harmful or beneficial but may have an effect in future generations.
Mutations do not always result in variation, but when they do, the variation is often in the form of entirely new alleles.

10. Types of mutations
1) Gene mutation – this is when a base change affects the DNA sequence of a single gene.

11. 2) Chromosomal rearrangements = block mutations
This is when blocks of genes within a chromosome are rearranged.

12. 3) Changes in chromosome number
Aneuploidy is the loss or gain of whole chromosomes.
Polyploidy is the loss or gain of complete sets of chromosomes.

13. 1. Gene mutations
Point mutations – changes in a single nucleotide. A nucleotide can be replaced by another (substitution), it can be removed (deletion) or an extra nucleotide can be added (insertion).
Tautomerism – abnormal base pairing.

14. Insertion mutations
When a single extra base is inserted into the DNA sequence a new sequence of codons can result due to a reading frame shift.
The protein that is then made is usually non-functional. The closer the insertion is to the start codon the more the protein will be affected.

16. Deletion mutations
A deletion of a base in a DNA sequence can have the same effect as an insertion mutation due to a reading frame shift.

18. Substitution mutations
Occurs when a base is substituted for another base.
Mis-sense substitution – change in codon leads to formation of protein but not the right protein. If the third base in a triplet is substituted, the amino acid may not actually be changed.
Non-sense substitution- the amino acid is changed to a stop codon resulting in a shorter, usually non-functional protein.

19. Mis-sense substitution

20. Non-sense substitution

21. Tautomerism
Some point mutations may result from bases with an abnormal number of hydrogen-bonding sites.
This results in abnormal base pairing. Pairs are called tautomers.

22. Inherited metabolic disorders – Page 146 biozone
More than 6000 diseases attributed to diseases in single genes.
Sickle cell disease
B- Thalassaemia
Cystic Fibrosis
Huntington Disease

23. Sickle Cell Disease
Single nucleotide substitution in HBB gene that codes for beta chain of haemoglobin.
Autosomal recessive mutation.

24. Animation – sickle cell

26. People that are heterozygous for sickle cell mutation are often resistant to malaria.
Studies have shown that African Americans, who have lived in malaria-free areas for as long as ten generations, have lower sickle cell gene frequencies than Africans -- and the frequencies have dropped more than those of other, less harmful African genes. Similarly, the sickle cell gene is less common among blacks in Curacao, a malaria-free island in the Caribbean, than in Surinam, a neighboring country where malaria is rampant -- even though the ancestors of both populations came from the same region of Africa.

27. Cystic fibrosis Autosomal recessive mutation.
Over 500 different recessive mutations of the CFTR gene have been identified.
Most common mutation (70% of sufferers) is a triplet deletion (AAA), which means the 508th amino acid of the CFTR gene is missing (deletion mutation).
Autosomal recessive mutation.

29. How does CF affect the body?
Cystic fibrosis (CF) is a chronic, life-shortening disease that occurs as a result of a genetic defect. The defective gene interferes with the body’s ability to transfer water and salt to and from cells. This causes secretions, which are normally thin and watery in healthy people, to become very thick and sticky. The thick secretions clog up organs and prevent them from working properly.
Lungs
Cystic fibrosis causes problems in the lungs when the thick mucus builds up and gets stuck in the airways.
When this happens:
Breathing passageways become blocked and air can’t get through.
Bacteria grow in the mucus collections and causes infection in the lungs, nose, and sinuses.

30. Pancreas
The pancreas is part of the digestive system. Its job is to secrete enzymes that are needed to digest food, and a hormone called insulin that controls blood sugar. Cystic fibrosis also causes these secretions to become thick.
When this happens:
The pancreatic ducts become clogged.
Enzymes can’t get past the obstruction.
Food is not digested properly and the body can’t absorb nutrients.
Eventually, the obstruction of the pancreas may cause scarring that damages the insulin-producing cells and prevents them from producing insulin. Insulin is not available to the cells, which causes blood sugar levels to rise. This condition is called insulin-dependent diabetes, which happens in about 15% of all CF patients.

31. Chromosome mutations Causes: Errors in crossing over at meiosis
mutagens

32. Types of chromosomal (block) mutations
Inversion – pieces of chromosomes are flipped over so the genes appear in the reverse order.
There is no loss of genetic material:

33. 2) Translocation
Pieces of chromosome are moved from one chromosome to another.
Can cause major problems when the chromosomes are passed to gametes. Some will receive extra genes, some will be deficient.

36. 3) Duplication
Pieces of chromosomes are repeated so there are duplicate segments.
One chromosome “donates” a segment of chromsome to another.
Some gametes will receive double the genes, others will have no genes for the affected segment.

38. 4) Deletion Pieces of chromosome are lost when:
a middle piece of the chromosome falls out and the two ends rejoin, so some genes are lost.
The end of a chromosome may break off and is lost.

40. Aneuploidy The diploid (2n) number of chromosomes in humans is 46.
The haploid (n) number of chromosomes in humans is 23.
Aneuploidy is the loss or gain of whole chromosomes. Extra or lost chromosomes can either be autosomes or sex chromsomes.
number

41. Some terminology Disomy = 2n (normal)
Monosomy = 2n – 1 eg. Turner’s syndrome
Trisomy = 2n + 1 eg. Down’s syndrome

42. Trisomy in human autosomes
1) Down’s syndrome: Trisomy 21

43. Causes of Down’s syndrome
92% of cases due to non-disjunction of chromosome 21 during meiosis
5% result from translocation of chromosome 21 (usually onto chromosome 14).

45. Non-disjunction in meiosis I
Non-disjunction in meiosis II
Normal meiosis

46. 2) Patau Syndrome: Trisomy 13
Usually die before 3 months
A newborn male with full trisomy 13 (Patau syndrome).  this baby has a cleft palate, atrial septal defect, inguinal hernia, and postaxial polydactyly of the left hand.

47. 3) Edward syndrome: Trisomy 18

48. Many aneuploidies show a “maternal age effect” with incidence increasing with age of mother.

49. Maternal age effect probably because: 1) all eggs are present at birth but meiosis occurs in stages, with meiosis not being complete until after fertilisation. Therefore, the eggs present in an older woman are old and there is a greater chance that errors in meiosis will occur.

50. Anueploidy in Human Sex chromosomes
The human sex chromosomes are XX for female and XY for male.
Abnormal sex chromosome configurations can arise when the sex chromosomes fail to separate properly during meiosis.

51. Faulty Sperm Production
Aneuploidy in human sex chromosomes may result from faulty sperm production. This results from the failure of the X and Y chromosomes to separate during meiosis.

52. Faulty egg production

55. Polyploidy
Is when a cell or organism contains three or more times the haploid number of chromosomes (3n or more).
Rare in animals, common in plants.
Polyploid animals include earthworms, shrimps and aphids.

58. Autopolyploidy Is a type of polyploidy.
Involves a multiple of identical sets of chromosomes from the same species.
Hybrid may be fertile or sterile depending on the number of chromosome sets. Hybrids with an even number of of chromosome sets will be fertile because chromosome pairing can occur at meiosis.

59. Autopolyploidy

60. Allopolyploidy
Involves the combination of chromosomes from two or more different species to form a hybrid.
Fertile polyploids may arise from doubling of the chromosome complement in the infertile hybrid (a process called amphiploidy).

62. Evolution of wheat