1. PREPARE BY: MISS LOCK SHU PING CHAPTER 7.0: MUTATION

2. Mutation MUTATION CLASSIFICATION AND TYPES GENE MUTATION CHROMOSOMAL MUTATION

3. 1.Explain mutation 2.Classify mutation into ‘gene mutation’ and ‘chromosomal mutation’. 3.State the types of mutation 4.Define mutagen 5.State types of mutagen

4. MUTATION ?

5. A permanent change in the amount, arrangement or structure of the DNA of an organism which can passed down to the next generation.

6. WHAT IS MUTATION? ‘ Changes in the genetic material (genes or chromosomes) of a cell’ Can be inherited if mutation occurs in reproductive cells during formation of gametes

7. Types of mutation -mutations that cause by mutagen - e.g: exposure to mutagen - mistakes happen spontaneously during DNA replication, DNA repair, or DNA recombination. -e.g: nondisjunction during meiosis ( details will be explain in 16.3) Based on the cause Spontaneous mutation Induced mutation

8. Spontaneous Mutation mistakes happen spontaneously during DNA replication, DNA repair, or DNA recombination.

9. Mutations that cause by mutagen A variety of agents increase the frequency of mutation

10. -Physical and chemical agents that induces changes in DNA Physical agent: Ultraviolet ray Ionizing radiation (X-ray, gamma ray, alpha particles, neutron and electron) Chemical agent: Mustard gas, nitrous acid, base analogue etc. Colchicine, ethidium bromide

11. Physical agent Effect Ionizing radiation -breaks in one or both strands (can lead to rearrangements, deletions, chromosome loss, death if unrepaired; this is from stimulation of recombination) -damage to/loss of bases (mutations) -crosslinking of DNA to itself or proteins UV radiationpyrimidine dimers in DNA

12. Chemical agent

13. Shortwave UV (UVA) Causes Thymidine Dimers

14. Mutation that causes by agent orange. About 500 000 children in Vietnam born with birth defects during Vietnam war

15. Mutant A mutated gene, alternatively, An organism carrying a gene that has undergone a mutation that shows new phenotype traits as a result from mutation

16. New phenotypes traits showed by this children as a result of mutation

17. Genetic Mutation 1.Base substitution 2.Base insertions 3.Base deletions 4.Base inversion Chromosomal Mutation 1.Structural change / Chromosome Aberration 2.Alterations of chromosome number  Aneuploidy  Euploidy / Polyploidy Mutation classification By effect on structure of gene (involve small scale mutation) of chromosome (involve large scale mutation)

18. Genetic Mutation Chromosomal Mutation Mutation Base substitution Base insertions Base deletions Base inversion

19. 1.Explain gene mutation 2.Classified gene mutation 3.Describe base substitution as point mutation 4.Explain frameshift mutation 5.Descibe base insertion as a frameshift mutation 6.Describe base deletion as a frameshift mutation

20. 16.2 Gene Mutation/ Point Mutation A type of mutation which involved A change in the nucleotide sequence of the DNA within a gene change the amino acid sequence and thus, changes the protein Different protein produced as the effect of mutation may not function as normal Example : sickle cell anemia

21. change the amino acid sequence changes the protein Change the DNA nucleotide sequence

22. AGCTTAAGCTTA TCGAATTCGAAT AGCGTTAAGCGTTA TCGCAATTCGCAAT AGCGTAAGCGTA TCGCATTCGCAT AGCTAAGCTA TCGATTCGAT AGTCTAAGTCTA TCAGATTCAGAT Normal Deletion Substitution Insertion Inversion Gene Mutation

23. Classification of gene mutation Base substitution – one or a few base pairs in the nucleotide sequences in genes is substitute (replaced) Base insertions – addition of 1 or a few base pairs in the nucleotide sequences in genes Base deletions – loss of 1 or a few base pairs in nucleotide sequences Base inversion – 2 base pairs or more are inverted in nucleotide sequence

24. Base Substitution : Base Insertion: THE FAT CAT ATE THE RAT THE FAT CAR ATE THE RAT THE FAT CAT ATE THE RAT THE FAT CAT CAT ETH ERA Base Deletion : Base Inversion : THE FAT CAT ATE THE RAT THE ATC ATA TET HER AT THE FAT CAT ATE THE RAT THE FAT CAT ATE THE TAR Analogy that can be made to show point mutation AGCGTAAGCGTA TCGCATTCGCAT AGCTAAGCTA TCGATTCGAT AGTCTAAGTCTA TCAGATTCAGAT AGCGTTAAGCGTTA TCGCAATTCGCAAT AGCTTAAGCTTA TCGAATTCGAAT Normal Deletion Substitution Insertion Inversion

25. one or a few base pairs in the nucleotide sequences in genes is replaced with another base pairs. Can cause changes in base sequence – results in changes of codon. E.g: (UAU change to UGU) 1 codon = 3 base/ nucleic acid (coding for 1 amino acid)

26. CAC-AAG-UAU-CAC-UAA his lys tyr his stop CAC-AAG-UGU-CAC-UAA his lys cys his stop Before mutation Substitution mutation Point Mutation a type of mutation that causes the replacement of a single base nucleotide with another nucleotide of the genetic material, DNA or RNA.  only on a small point of a chromosome

27. Changes in codon:  Leads to amino acid changes  The altered codon codes for different amino acid  Changes a codon to stop codon (UAG / UAA / UGA )  Leading to a nonfunctional protein Missense mutation nonsense mutation

28. Changes in codon Nonsense Mutation  changes a codon to stop codon  Leading to a nonfunctional protein

29. Changes in codon  Leads to amino acid changes  the altered codon codes for an amino acid that is not the right sense. Missense Mutations

30. Changes in codon Silent Mutations  have no effect on the encoded protein.  a change in a base pair transform one codon into another that translated into the same amino acid.  happens because of redundancy in the genetic code.

31. AGU  AGC SER  SER Silent Mutations

32. Changes in codon:  Leads to amino acid changes  The altered codon codes for different amino acid  Changes a codon to stop codon (UAG / UAA / UGA )  Leading to a nonfunctional protein Missense mutation nonsense mutation

33. Base substitution CAC-AAG-UAU-CAC-UAA his lys tyr his stop CAC-AAG-UGU-CAC-UAA his lys cys his stop CAC-AAG-UAG his lys stop Before mutation Missense mutation Nonsense mutation Differences between missense and nonsense mutation is missense mutation altered codon codes for different amino acid while nonsense mutation alteres codon to stop codon.

34. EFFECT OF BASE SUBSTITUTION Sickle cell Anemia

35. SICKLE-CELL ANEMIA Missense mutation Defective red blood cell Abnormal Hb – Sickle (S) shape Hb ~ 4 polypeptide chain (2-  & 2-  ) Encode by different gene

36. HOW SICKLE- CELL ANEMIA HAPPEN? Happens because substitution mutation Amino acid valine replaces glutamic acid at a single position in the protein (  -strand) Patient suffer from anemia ~ Hb-S stiff & tend to accumulate in small capillary Hb is not efficient of transporting oxygen

37. Missense mutation

38. Sickle cell Anemia abnormal haemoglobin crystallizes & erythrocyte is pulled into a sickle shape the cells fragment easily or clump together to clog the capillaries (and less O 2 is transported)

39. TRY THIS… A.GGCATT B.GGCCATT C.GGCTT D.GCGCTT State what type of gene mutation below: Normal DNA : GGCCTT GGCATT BASE SUBSTITUTION GGCCATT BASE INSERTION GGCTT BASE DELETION GCGCTT BASE INVERSION

40. WHAT ARE THE DIFFERENCES BETWEEN MISSENSE AND NONSENSE MUTATIO N? Missense mutation altered codon codes for different amino acid nonsense mutation altered codon to STOP codon. (UAG / UAA / UGA )

41. What is the genetic disorder shown above? Sickle- cell anemia What type of gene mutation that cause this genetic disorder to happen? Why? Because of substitution mutation. Amino acid valine is replaced by glutamic acid at a single position in the protein (  -strand)

44. Point Mutations in Coding Sequences Missense – changes amino acid Nonsense – creates stop codon Frameshift – alters remainder of reading frame results in completely different amino acid sequence.

47. FRAME-SHIFT MUTATIONS

48. Involve insertion/deletion of a base pair or more into the nucleotides sequence of DNA Many of these deletions/insertion start in the middle of a codon

49. Shifting the reading frame by one or two bases Frame shift mutations cause the gene to be read in the WRONG three base groups (codon)

50. Example Insertion of U base Change the sequence of amino acids Deletion of C base Resulting in stop codon-no further amino acid produces

51. From the mutation point, it abrupts the coding sequence of amino acid. Changes in codons results in changes in amino acids All the nucleotides downstream of the deletion/ insertion will be improperly grouped into codons. different polypeptide is produced.

52. Frame-shift Mutations The result will be –extensive missense, ending sooner or –later in nonsense - premature termination. Effect ~ usually harmful to human e.g: Major thalasemia (mutant homozygote alleles)

53. ACACGCACUCCC Amino acid 1 Amino acid 2 Amino acid 3 Amino acid 4 Codon 1 Reading frame in mRNA Frame-shift Mutations Normal Mutant ACACG CACUCCC Codon 2Codon 3Codon 4 Codon 1 Codon 2Codon 3 Amino acid 1 Amino acid 2 Amino acid 3 Reading frame is shift one base infront

54. Nonsense Non frameshift Extensive missense

55. Additions of nucleotide pairs in a gene All the nucleotides that downstream of the insertion will improperly group into codons. Analogy: THE FAT CAT ATE THE RAT THE FAT CAT CAT ETH ERA insertion improperly group into codons

56. Extensive missense

57. Losses of nucleotide pairs in a gene All the nucleotides that downstream of the deletion will improperly group into codons. Analogy: –THE FAT CAT ATE THE RAT –THE ATC ATA TET HER AT improperly group into codons

58. Extensive missense

59. Eg. of disorder due to base deletion is thalasemia –deletion of nucleotide base pairs for genes which –control the production of Hb α and β chains –major thalassemia causes serious anaemia

60. 2 base pairs or more in nucleotide sequence are inverted Change the codons => changes in amino acid Usually the effect is minor phenotype abnormality Normal code: AGA-GTC-TTC ser glu lys Base inversion: AGA-TGC-TTC ser thr lys

61. Base Substitution Base Insertion Base Deletion Base Invertion

64. Genetic Mutation Chromosomal Mutation Mutation Chromosome aberration Alterations in chromosome number

65. 1.Explain chromosomal mutation 2.Classify chromosomal mutation into chromosomal aberration and chromosomal number alteration. 3.Explain chromosomal aberration 4.State and describe types of chromosomal aberration Chromosomal Mutation

66. Definition: Abnormalities ~ in chromosomal structure (chromosome aberration) & changes in chromosome number (aneuploidy / euploidy)

67. Types of chromosome mutation Chromosome aberration Alterations in chromosome number Euploidy (Polyploidy) Aneuploidy Deletion Inversion Translocation Duplication Structural change

68. Chromosome Aberration Involving the breakage of chromosome and rearrangement a certain segment or parts of chromosome 4 types : Deletion Inversion Translocation Duplication

69. DELETION Chromosomal Mutations:

70. DELETION DUPLICATION Chromosomal Mutations:

71. DELETION DUPLICATION INVERSION Chromosomal Mutations:

72. DELETION DUPLICATION INVERSION TRANSLOCATION Chromosomal Mutations:

73. the lost of 1 segment containing 1 or more genes ABCDEFGHIABCDEFGHI Break off ABCABC GHIGHI DEFDEF ABCGHIABCGHI Losing middle section Deletion

74. Example: Cri-du-chat syndrome 1.due to deletion of a section of the short arm of chromosome 5 2.characteristics: small head unusual facial features mentally retarded cries like the mew of a cat 3. Usually dies in infancy/ early childhood krē-du ̇ - ˈ shä-

75. Example: Cri-du-chat syndrome

76. small head unusual facial features mentally retarded cries like the mew of a cat

77. a region of a chromosome breaks off and rotates through 180° before rejoining the chromosome ABCDEFGHIABCDEFGHI break off break off ABCFEDGHIABCFEDGHI ABCABC GHIGHI DEFDEF Inversion

78. Centromere lies within inverted region Centromere lies outside inverted region Inversion

80. Involves a region of a chromosome breaking off and rejoining either the other end of the same chromosome or another non-homologous chromosome Translocation ABCDEFGHI chromosome 1 MNOPQ RS chromosome 2 ABPQ RS FGHICDENOM reciprocal translocation

81. Most common: RECIPROCAL TRANSLOCATION [ 2 non-homologous chromosomes exchange fragments ]

82. In non-reciprocal translocation, a chromosome transfers a fragment without receiving any in return Example: Robertsonian translocation

83. Robertsonian translocation involves breaks at the extremes ends of the short arms of two nonhomologous chromosomes (13,14,15, 21 and 22).

84. a region of a chromosome becomes duplicated; an additional set of genes exists ABCDEFGHIABCDEFGHI Additional set of genes ABCDEFGHIFGHIABCDEFGHIFGHI Duplication

87. Differences between chromosomal mutation and gene/point mutation Chromosomal mutationGene/point mutation A process that cause changes in chromosome structure or number A process that causes changes in the base sequence of the DNA Types of chromosomal mutation are chromosomal aberration and alteration in chromosome number. Types of gene mutation are base substitution, base inversion, base deletion and base insertion. No frameshift mutationBase deletion and base insertion cause frameshift mutation No production of non- functional protein Leads to production of non- functional protein

88. 1.The DNA nucleotide base sequence can be altered in several ways.Which of the following is NOT involved in gene mutation? A.Substitution B.Inversion C.Deletion D.Translocation

89. The figure below shows a pair of homologous chromosomes during prophase I. What could have cause this? ABCGH AB C GH D F E A.Substitution B.Inversion C.Deletion D.Duplication

90. The figure shows two types of chromosomal mutations to the genetic sequence below. A B C D E F G H A B E D C F G HA B E F G H I II What are the processes that cause the chromosomal mutation I and II above? III AInversionDeletion BInversionDuplication CDeletionInversion DTranslocationDeletion

91. Try this…. Determine the types of mutation shown in the figure below. Normal gene sequence ABCDE FGH (i)ABCE FGH (ii)ADCBE FGH (iii)ABCBCDE FGH (iv)ABCDE MNOPQ