1. Mutations Chapter 12 127/06/2016

2. Learning Intentions To investigate mutations and chromosome abnormalities, specifically.... –Alteration of base type or sequence. –Non-disjunction and its effects on human You should be able to examine photographs of karyotypes of individuals and recognise conditions such as –Down’s Syndrome –Turner’s Syndrome –Kleinfelter’s Syndrome 27/06/20162

3. Mutations A mutation is a change in the structure or amount of an organisms genetic material. This mutation can by a tiny change in DNA structure or can be a large scale change in chromosome structure or number When a change in genotype produces a change in phenotype, the individual is called a mutant 27/06/20163

4. Vocab Phenotype: individual's observable traits Ex. such as height, eye color, and blood type Genotype: individual's collection of genes Ex. XX or XY Karyotype: is the number and appearance of chromosomes in the nucleus of a eukaryotic cell 27/06/20164

5. Gene Mutations = Alteration of the base or sequence Here there is a change in one or more of the nucleotides in a strand of DNA There are four main types of mutation –POINT MUTATIONS 1.Substitution Mutations 2.Inversion Mutations –FRAMESHIFT MUTATIONS 3.Insertion Mutations 4.Deletion Mutations More specifically each of the has had an alteration in one or more codons for one or more specific amino acids leading to a change in the protein that is synthesised. 5

6. Point mutations (substitution and inversion) For a protein to work properly it must have the correct sequence of amino acids. If there is a substitution or inversion mutation it usually brings about a minor change (i.e. one different amino acid). Organism is affected only slightly or not at all. However if the substituted amino acid occurs at a critical point in the amino acid a major defect may arise. –(e.g. Formation of haemoglobin S in sickle cell anaemia.) 6

7. 27/06/20167

8. Substitution – one base is swapped for another – e.g. U for C 8

9. Another example! 27/06/20169

10. Substitution another example Dr. Cocozza is crazy! ATG TCA AAT CGA Dr. Cocozza is ______! ATG TCA AAT GGA 27/06/201610

11. Inversion Inversion of two or more nucleotides, i.e. Positions become back to front (inverted)! 27/06/201611

12. Frameshift Mutations - (Insertions or deletions) Here a there is a major change, since it leads to a large portion of the gene’s DNA to be misread, This results in the produced protein differing from the normal protein by many amino acids which is usually non-functional. e.g. If a protein is an enzyme which catalyses an essential step in a metabolic pathway, then the pathway becomes disrupted, for example PHENYLKETONURIA. 27/06/201612

13. 1327/06/2016

14. 14

15. Albinism 27/06/201615

16. Frameshift example 27/06/201616

17. Frequency of mutation In the absence of outside influences, gene mutations arise spontaneously and at random but occur rarely. Mutation rate varies from species to species, allele to allele. Most mutant alleles are recessive – expressing themselves when two recessive alleles meet in future generations. However a few mutant alleles are expressed by the first generation to inherit them because they are either dominant (e.g. Huntington's Chorea) or sex linked (e.g. haemophilia). 27/06/2016Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities 17

18. Mutagenic agents – Increases mutation rate. These include –A variety of chemicals act as mutagens. E.g. Bromouracil, are structurally similar to DNA bases, and are inserted in place of normal bases. Ethidium bromide has a structure that allows it to wedge within the DNA double helix Peroxides and mustard gas, chemically modify DNA. –Exposure to high-energy radiation (bombardment by alpha, beta, or gamma particles) or ultraviolet light can have a similar effect. 27/06/2016 18

19. Example of chemical mutations 27/06/2016Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities 19

20. The Chernobyl Babies – Radiation causes birth defects 27/06/2016Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities 20

21. The Movie? 27/06/201621

22. Chromosomal Anomalies Gamete: A cell whose nucleus unites with that of another cell to form a new organism (egg and sperm). A gamete contains only a single (haploid) set of chromosomes. Haploid means ½ the total amount of genetic material needed. Meiosis: a type of cell division in which a nucleus divides into four daughter nuclei, each containing half the chromosome number of the parent nucleus: occurs in all sexually reproducing organisms in which haploid gametes 22

23. 2327/06/2016

24. Chromosomal Abnormalities Chromosomes can be affected by mutations which bring about large scale changes to the genetic material. One type happens during meiosis in humans when unusual gametes can be formed which contain 22 or 24 chromosomes instead of the normal 23 This leads to the formation of zygotes with abnormal chromosome complements. This is called non-disjunction 27/06/201624

25. Non-disjunction during meiosis. These abnormal gametes are formed when a spindle fibre fails and one of the pair of homologous chromosomes fail to become separated 27/06/2016Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities Extra copy Lack a chromosome Extra copy

26. Down’s Syndrome 27/06/201626

27. Down’s Syndrome Due to non-disjunction of chromosome 21. Abnormal egg (n=24) + normal sperm (n=23) abnormal zygote (n=47). An extra copy of chromosome 21 is seen in the karyotype of someone with Down’s syndrome The affected individual is characterised by mental retardation and distinctive physical features Egg mother cells of older women (80% due to maternal age) tend to be more prone to non- disjunction at meiosis. 27/06/201627

28. Down’s Syndrome (aka 21) Karyotype 27/06/201628

29. Turner’s Syndrome 27/06/201629

30. 3027/06/2016

31. Turner’s Syndrome – female only If a gamete which possesses no sex chromosomes meets and fuses with a normal X gamete, the zygote formed has the following chromosome complement - 2n = 44 + XO Individuals are always female and short in stature Their ovaries do not develop so they are infertile and fail to develop secondary sexual characteristics e.g. breast development and menstruation. Happens 1:2,500 live births 27/06/201631

32. Turner’s Syndrome 27/06/201632

33. Klinefelter’s Syndrome 27/06/201633

34. Klinefelter’s Syndrome- Male Only 27/06/201634

35. Klinefelter’s Syndrome – Male only Happens when: –An XX egg is fertilised by a normal Y sperm –OR an normal X egg is fertilised by an XY sperm Resulting with chromosome complement 2n = 44 + XXY Individuals are always male and possess male sex organs However they are infertile since their testes only develop to half the normal size and fail to produce sperm Testes produce low levels of testosterone so facial hair, deepening of voice are only weakly expressed. Some sufferers develop small breasts. Occurs in 1:1,000 live male births 27/06/201635

36. 3627/06/2016

37. Chromosome Mutations Changes in number and structure of entire chromosomes Original Chromosome ABC * DEF DeletionAC * DEF DuplicationABBC * DEF InversionAED * CBF TranslocationABC * JKL GHI * DEF

38. Remember… There are two ways in which DNA can become mutated: –Mutations can be inherited. Parent to child –Mutations can be acquired. Environmental damage Mistakes when DNA is copied –They can be harmful, helpful or neutral.

39. 3927/06/2016