1. FEBRUARY 11, 2013 CAPE BIOLOGY MRS. S. HAUGHTON
MUTATIONS
FEBRUARY 11, 2013
CAPE BIOLOGY
MRS. S. HAUGHTON

2. A mutation is a change in the amount, arrangement or structure of the DNA of an organism.
Produces a genotypic change.
May be passed on to cells derived from the original by mitosis or meiosis.

3. May result in the change in appearance of a characteristic in a population.
Mutations in gametes are inherited by offspring.
Mutations in somatic cells are only passed to daughter cells during mitosis.

4. TYPES OF MUTATIONS There are two types:
Chromosomal – change in the amount or arrangement of DNA on a chromosome or of chromosomes themselves (aka chromosomal aberration).
A change in the structure of the DNA at a single locus (aka point mutation).

5. FREQUENCY OF MUTATIONS
Occur randomly and spontaneously.
Frequency and rates vary among organisms.

6. CAUSES OF MUTATIONS Frequency increased by:
X-rays, high energy electromagnetic radiation (UV-rays and gamma rays)
high energy particles such as α and β
Cosmic radiation
Neutrons
Substances (mutagens) such as mustard gas, caffeine, formaldehyde, colchicine, drugs, food preservatives, pesticides and some components of tobacco.

7. CHROMOSOME MUTATIONS

8. May affect several genes
May affect the phenotype more strongly than gene mutations
Changes in number occur more frequently during meiosis but can also occur during mitosis (but not as detrimental).

9. ANEUPLOIDY The loss or gain of a single chromosome.
Half the daughter chromosomes have an extra chromosome (n+1), (2n+1) while the other half have a chromosome missing (n-1), (2n-1).
Arises from a failure of a pair or pairs of homologous chromosomes to separate during anaphase I of meiosis.

10. This will later affect separation at anaphase II because the gamete formed will have too many or too few chromosomes.
This is called non-disjunction.
When fused with a normal haploid gamete the resulting zygote will have an odd number of chromosomes.

13. Zygotes with less chromosomes usually do not develop.
Those with more chromosomes may develop  sever abnormalities result.
E.g. Down’s syndrome is non-disjunction resulting in trisomy where 2n=47 and not 46; results from the non-disjunction of chromosome number 21.

14. Which karyotype belongs to the person with Down’s syndrome?

16. E.g. non-disjunction of the male and female sex chromosomes may occur affecting the secondary sexual characteristics, fertility and sometimes intelligence.

17. DISORDERS CAUSED BY NON-DISJUNCTION

18. Failure of chromosome to separate during division
Mitosis
Cell dies, organism is not harmed
Meiosis
Results in an abnormal gamete that will produce abnormal offspring

19. Down Syndrome Extra chromosome at the 21st position Enlarged tongues
Small, round ears
Heart defects
Stubby fingers and toes
Mental retardation

20. Turner Syndrome phenotype-female small functioning ovaries short
• XO
phenotype-female
small functioning ovaries
short
no breast development

23. Klinefelter Syndrome XXY at 23rd position
small testes, no sperm development
enlarged breast development
tall stature

26. Cri-du-chat Partial deletion from chromosome # 5
Baby’s cry sounds like a cat
Severe mental retardation
Multiple anatomical malformations

28. EUPLOIDY (POLYPLOIDY)
Increase in entire haploid SETS of chromosomes.
This occurs when somatic cells contain multiples of the haploid number of chromosomes.
The prefixes tri-, tetra- etcetera denote the extent to which polyploidy occurs in cells.

29. More common in plants than animals.
In polyploid animals, the extra chromosomes make gamete formation during meiosis prone to error which causes fewer offspring to be made.

30. Half the 300,000 known species of angiosperms are polyploid.
Since plants are able to vegetatively propagate themselves, they are able to reproduce even though they are polyploid, because they do not require gametes for this asexual reproduction.

31. Polyploidy is also associated with advantageous features such as size, hardiness and resistance to disease.
This is called hybrid vigour.
Most of our domestic plants are polyploids and produce large fruits, storage organs, flowers or leaves.

32. Two forms of polyploidy exist and they are:
Autopolyploidy
Allopolyploidy

33. AUTOPOLYPLOIDY
Is the result in the increase in the number of chromosomes within the same species.
For example if after mitosis, the cytokinesis does not occur, instead of two daughter cells, we will have one tetraploid cell with a large nucleus.
Subsequent divisions will yield tetraploid cells.

34. The cytoplasm will increase as well to preserve the cell structure.
Hence this region of the plant will contain enlarged cells which may make that region itself enlarged.
Colchicine is a substance that can cause this to occur because it inhibits anaphase.
Autopoluploidy gives rise to endomitosis in some animals (Drosophila and human liver cells).

36. ALLOPOLYPLOIDY
Occurs when the chromosome number in a sterile hybrid becomes doubled and produces fertile hybrids.
Hybrids from different species are usually sterile because their chromosomes cannot form homologous pairs during meiosis.
This is called hybrid sterility.

37. But if multiples of the original haploid number of chromosomes occur, a new species is produced, which is fertile with polyploids like itself, but infertile with both parental species.

38. Most allopolyploidy species have a diploid chromosome number which is the sum of the diploid numbers of their parent species.
E.g. rice grass (2n=122) is the fertile hybrid of sparta grass 1 (2n=60) and sparta grass 2 (2n=62).
The hybrid has some characterisitcs of both parental species.

39. Another example, the species of wheat used to make bread (2n=42) was bred over thousands of years from:
Wild wheat (2n=14),
Wild grass (2n=14) which gave Emmer wheat (2n=28)
Emmer wheat was crossed with another wild grass (2n=14) to give bread wheat (2n=42)

41. STRUCUTRAL CHANGES WITHIN CHROMOSOMES

42. Deletion One or more genes are lost from a chromosome during division
Occurs if homologous chromosomes cross over unequally during meiosis

43. Duplication
Chromosome receives an extra piece, which duplicates some genes

44. Translocation
A whole chromosome or piece of chromosome attaches to a chromosome in a different pair
Results in extra or lost genes
May break up important gene arrangements and change the phenotype of the organism

45. Translocation

46. Inversion
Part of chromosome breaks off and reattaches itself in reverse order
May cause no change because it is not losing genes
Changes the arrangement and may upset important gene interactions

47. Inversion

48. Summary of chromosomal mutations

49. Summary of chromosomal mutations

50. GENE OR POINT MUTATIONS

51. There are three different ways gene mutations can occur;
Base addition - where one or more additional bases are added - CCT GAG GAG may become CCA TGA GGA G.

52. Base substitution - where one based takes the place of another - CCT GAG GAG may become CCT GTG GAG.

53. Base deletion - where one or more bases are deleted from the sequence - CCT GAG GAG may become CCG AGG AG.

54. Addition and deletion usually have a major effect on structure, and most often completely breaks the polypeptides that it codes for function.
They cause frame shifts in the base sequence, causing a ripple change effect down the line for example ;
CCT-CCT-GAG-CCG-GAG-AGG

55. If we remove the bolded letter during base deletion, we are left with
CCT-CCT- AGC-CGG-AGA-GG
(CCT-CCT-GAG-CCG-GAG-AGG)
Which is a completely different sequence, and likely completely useless - especially since the last triplet code is not a triplet at all.

56. However, base substitutions can sometimes have no effect, and are said to be a silent mutation - usually only if the substitution results in a STOP triplet prematurely in the sequence, and the protein synthesis will never complete.

57. EXAMPLES Sickle Cell Anemia
A base substitution with significant effect is shown in sickle cell anemia where a small difference in the gene that codes for one of the amino acid chains in haemoglobin causes a big problem.

58. When the haemoglobin is not combined with oxygen, the error causes haemoglobin to be much less soluble, causing it to stick together forming long fibres inside the red blood cells, pulling them out of shape or 'sickling' them.
This makes them useless at transporting oxygen and can cause them to get stuck in capillaries.

59. Phenylketonuria
Another example of a base substitution causing issues is phenylketonuria, and affects an enzyme that converts phenylalanine to tyrosine (which is then converted to melanin, the brown pigment in skin and hair).
If phenylalanine cannot be converted to tyrosine, then tyrosine is not converted as much as it should be to melanin, causing lighter skin and hair colour.

60. It can also cause a serious health problem in young children, with phenylalanine accumulating in the blood and tissue fluid.
Testing can prevent serious brain damage, since if the child shows positive for PKU, they will be placed on a phenylalanine-free diet.

61. IMPLICATIONS OF MUTATION

62. Consequences of Gene Mutations
In gametes can affect whole organism made from the gametes
In somatic cells can go unnoticed but may lead to tumours both benign or malignant which live parasitically on healthy cells

63. Consequences of Chromosomal Mutations
Most are lethal
20% in humans lead to spontaneous abortion.
50% exhibit chromosomal abnormalities
May bring gene sequences together that are actually beneficial
Increases variation and size of gene pool

65. GENE MUTATIONS

66. SICKLE CELL DISEASE Affects beta chain of haemoglobin
Base substitution on chromosome 11 from adenine to thymine causes placement of amino acid valine instead of glutamic acid in polypeptide chain.

67. CYSTIC FIBROSIS Chromosome 7
Deletion of 3 bases (codon 508) in the cystic fibrosis transmembrane regulator gene
Codon deletion omits phenylalanine from positiom 508 in polypeptide chain

68. PHENYLKETONURIA Chromosome 12 affected
Contains PAH gene which codes for PAH enzyme that catalyses phenylalanine to tyrosine.
Single base substitution, GT to AT. The protein will in fact be 52 amino acids shorter than normal (classic).
This mutation is by a substitution from CGG to TGG in exon 12 (mild).
Substitution from G to A within the Arg 158 position causing the amino acid to be replaced by Gln (mild).

69. HUNTINGTON’S CHOREA
Insertion of numerous repeats of codon CAG on chromosome 4
Normal chromosomes have repeats
Abnormal chromosomes have repeats

70. CHROMOSOMAL MUTATIONS

71. DOWN’S SYNDROME Extra chromosome 21 Trisomy
Affects somatic chromosomes
Due to non-disjunction

72. TURNER’S SUNDROME Missing X chromosome in females Only one X
Affects sex chromosomes
Due to non-disjunction

73. KLINEFELTER’S SYNDROME
Extra X chromosome in males
Affects sex chromosomes
Due to non-disjunction

74. Homework Write a 150 word essay explaining the role of mutations:
Sickle cell anaemia
Cystic fibrosis
Phenyketonuria
Huntington’s chorea
Down’s syndrome
Klinefelter’s syndrome
Turner’s syndrome