Chapter 13: Mutations and Chromosomal Abnormalities

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Chapter 13 Mutations and Chromosomal
Abnormalities
Higher Human Biology
Unit 1 Cell Function and Inheritance
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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
• Downs Syndrome
• Turners Syndrome
• Kleinfelters Syndrome

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You need to know these words
Klinefelters Syndrome
Insertion
Nucleotide
Mutant
Deletion
Gene Mutation
Substitution
Chromosomal Abnormality
Point mutation
Inversion
Frequency of mutation
Albinism
Frameshift
Cystic fibrosis
Non-disjunction
Mutagenic Agents
Phenylketonuria
Downs Syndrome
Turners Syndrome
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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
• 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.

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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 genes 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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PhenylketonuriaBackground 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
  Albinos 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.....
• Homozygous for the mutant allele Make abnormally
  thick and sticky mucous leading to lung
  congestion and blockage of the pancreatic duct
  CYSTIC FIBROSIS.
• 12500 births in Britain
• 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 Qus 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
Lack a chromosome
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Downs Syndrome

• Due to non-disjunction of chromosome 21.
• Abnormal egg (n24) normal sperm (n23)
  abnormal zygote (n47).
• An extra copy of chromosome 21 is seen in the
  karyotype of someone with Downs 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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Downs Syndrome (aka 21) Karyotype
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Symptoms of Downs
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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.

44 XX
44 XX
44 XY
44 XY
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Turners 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 12500 live births

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Turners Syndrome
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Turners 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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Klinefelters 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 11000 live male births

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Klinefelters Syndrome
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Klinefelters Syndrome
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Task Torrance pg 100 Qus 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)