Higher Human Biology
Unit 1: Cell Function and
Inheritance
Chapter 13: Mutations and
Chromosomal Abnormalities
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Chromosomal Abnormalities
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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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Chromosomal Abnormalities
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You need to know these words
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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
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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.
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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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Substitution – one base is
swapped for another – e.g. U for C
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Inversion
• Inversion of two or more nucleotides, i.e.
Positions become back to front (inverted)!
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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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Insertion
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Insertion
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Deletion
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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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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
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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.
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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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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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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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Albinism
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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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Cystic fibrosis:
due to gene mutation
• If the info on the gene for the glycoprotein
is altered.... Two outcomes.....
1. 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
2. Heterozygous for the mutant allele: they carry
the mutant allele masked in their genotype
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Cystic fibrosis
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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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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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Example of chemical mutations
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The Chernobyl Babies –
Radiation causes birth defects
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Task: Torrance pg 97 Qu’s 1-4
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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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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
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Chromosomal Abnormalities
Lack a
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chromosome
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 nondisjunction at meiosis.
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Down’s Syndrome
(aka 21) Karyotype
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Symptoms of Down’s
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Non-disjunction of Sex
Chromosomes
If human sex chromosomes are affected by non-disjunction
during meiosis then unusual gametes are formed.
Normal
situation
44+ XX
Normal
Meiosis
Abnormal
situation
Egg
mother 44+ XX
cell.
Normal
situation
44+ XY
Non-disjunction at
1st meiotic division
Abnormal
situation
Sperm
mother
cell.
Normal
Meiosis
44+ XY
Non-disjunction at
1st meiotic division
22+ X
22+ X
22+ XX
22
22+ X
22+ Y
22+ XY
22
22+ X
22+ X
22+ XX
22
22+ X
22+ Y
22+ XY
22
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Normal eggs
Mrs Smith: Ch13: Mutations an
Chromosomal
Abnormal
eggs Abnormalities
Normal sperm
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Abnormal sperm
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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Chromosomal Abnormalities
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Turner’s Syndrome
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Chromosomal Abnormalities
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Turner’s Syndrome
Webbed neck, unusual fingers, short stature, low
neckline are all features of the condition. Heart,
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hearing
and visual problems
can also occur
Chromosomal Abnormalities
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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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Klinefelter’s Syndrome
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Klinefelter’s Syndrome
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Task: Torrance pg 100 Qu’s 1-3
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Essay Question Guide to H-Grade
essays pg 62
Discuss how genetic
abnormalities can
result in certain
human conditions.
(15)
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