1. Chapter 13: Mutations and Chromosomal Abnormalities
Higher Human Biology
Unit 1: Cell Function and Inheritance
Chapter 13: Mutations and Chromosomal Abnormalities
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

2. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

3. You need to know these words
Klinefelter’s Syndrome
Insertion
Nucleotide
Mutant
Deletion
Gene Mutation
Substitution
Chromosomal Abnormality
Point mutation
Inversion
Frequency of mutation
Albinism
Frameshift
Non-disjunction
Cystic fibrosis
Phenylketonuria
Mutagenic Agents
Down’s Syndrome
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Turner’s Syndrome

4. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

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
Substitution Mutations
Inversion Mutations
FRAMESHIFT MUTATIONS
Insertion Mutations
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.
Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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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).Here 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.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

7. Substitution – one base is swapped for another – e.g. U for C
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

8. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Inversion
Inversion of two or more nucleotides, i.e. Positions become back to front (inverted)!
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

9. 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 ctalyses an essential step in a metabolic pathway, then the pathway becomes disrupted, for example PHENYLKETONURIA.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

10. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Insertion
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

11. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Insertion
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

12. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Deletion
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

13. Phenylketonuria Background to Phenylketonuria
Phenylalanine and tyrosine are two amino acids that humans obtain from protein in their diet. During normal metabolism, excess phenylalanine is acted upon by an enzyme (phenylalanine hydroxide).
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

14. Phenylketonuria: aka - PKU
PKU is a hereditary disorder caused by a genetic defect which disrupts this metabolic pathway.
An affected person lacks the normal allele of the gene required to make the enzyme Phenylalanine Hydroxide
Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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15. Phenylketonuria: Continued
Owing to this inborn error in metabolism, phenylalanine is no longer converted to tyrosine.
Instead it undergoes alternative pathways which produces toxins which affect the metabolism of brain cells and severely limit mental development.
Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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16. Screening for PKU – More in chapter 14
In Britain, newborn babies are screened for PKU, and sufferers are put on a diet containing minimum phenylalanine.
As a result the worst effects of PKU can be kept to a minimum.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

17. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Albinism
Albinism results from a mutation which prevents the formation of enzyme 3 (Melanocyte Tyrosinase). As a result albinos fail to synthesise melanin.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

18. Albinism – the symptoms
Due to the total lack of the pigment melanin Albino’s have characteristic
Very pale skin which fails to tan.
White hair
The colour of the iris is usually blue/gray or light brown with some people having a reddish or violet hue reflected through the iris.
In some cases there is vision problems.
They must avoid ultraviolet radiation and may require to ware tinted glasses to assist with photophobia.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

19. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Albinism
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

20. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Cystic Fibrosis
Mucus is a slimy substance secreted by the inner lining of the wind pipe and intestine.
Mucus is made of a glycoprotein which makes it thick, slimy and perfect for protection and lubrication.
The genetic information for coding this glycoprotein is on chromosome 7.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

21. Cystic fibrosis: due to gene mutation
If the info on the gene for the glycoprotein is altered.... Two outcomes.....
Homozygous for the mutant allele: Make abnormally thick and sticky mucous leading to lung congestion and blockage of the pancreatic duct = CYSTIC FIBROSIS.
1:2500 births in Britain
Heterozygous for the mutant allele: they carry the mutant allele masked in their genotype
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

22. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Cystic fibrosis
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

23. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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).
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

24. 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.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

25. Example of chemical mutations
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

26. The Chernobyl Babies – Radiation causes birth defects
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

27. Task: Torrance pg 97 Qu’s 1-4
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

28. 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
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

29. 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
Extra copy
Extra copy
Lack a chromosome
Lack a chromosome
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

30. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
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.
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

31. Down’s Syndrome (aka 21) Karyotype
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

32. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Symptoms of Down’s
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

33. Non-disjunction of Sex Chromosomes
If human sex chromosomes are affected by non-disjunction during meiosis then unusual gametes are formed.
Normal
situation
Abnormal
Egg mother cell.
Meiosis
Non-disjunction at 1st meiotic division
22+ X
22+ XX 22
Normal eggs
Abnormal eggs
Normal
situation
Abnormal
Spermmother cell.
Meiosis
Non-disjunction at 1st meiotic division
22+ X
22+ Y
22+ XY 22
Normal sperm
Abnormal sperm
44+ XX
44+ XX
44+ XY
44+ XY
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

34. 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 1:2500 live births
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

35. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Turner’s Syndrome
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

36. Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities
Turner’s Syndrome
Webbed neck, unusual fingers, short stature, low neckline are all features of the condition. Heart, hearing and visual problems can also occur
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

37. 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 1:1000 live male births
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

38. Klinefelter’s Syndrome
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

39. Klinefelter’s Syndrome
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

40. Task: Torrance pg 100 Qu’s 1-3
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Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

41. Essay Question Guide to H-Grade essays pg 62
Discuss how genetic abnormalities can result in certain human conditions. (15)
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Mrs Smith