chapter 13: mutations and chromosomal abnormalities

Chapter 13: Mutations and Chromosomal Abnormalities

Higher Human Biology

Unit 1: Cell Function and Inheritance

21/04/23 1Mrs 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


You need to know these words

21/04/23 Mrs Smith: Ch13: Mutations an Chromosomal Abnormalities

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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


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.

21/04/235Mrs Smith: Ch13: Mutations an

Chromosomal Abnormalities

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


Inversion• Inversion of two or more nucleotides, i.e. Positions become back to front

(inverted)!


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


Deletion


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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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


Chromosomal Abnormalities14

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.


Chromosomal Abnormalities15

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



• 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


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

Lack a chromosome

Lack a chromosome

Extra copy

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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.


Down’s Syndrome (aka 21) Karyotype


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.

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Normal situation

Abnormal situation

Egg mother cell.

Normal Meiosis

Non-disjunction at 1st meiotic division

22+ X

22+ X22+ X

22+ X 22+ XX

22+ XX 22

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Normal eggs Abnormal eggs

Normal situation

Abnormal situation

Spermmother cell.

Normal Meiosis

Non-disjunction at 1st meiotic division

22+ X

22+ Y22+ X

22+ Y 22+ XY

22+ XY 22

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Normal sperm Abnormal sperm

44+ XX 44+ XX 44+ XY 44+ XY


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


Turner’s Syndrome


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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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


Klinefelter’s Syndrome


Task: Torrance pg 100 Qu’s 1-3


Essay Question Guide to H-Grade essays pg 62

Discuss how genetic abnormalities can result in certain human conditions. (15)

21/04/23 Mrs Smith 41

chapter 13: mutations and chromosomal abnormalities

Documents

chromosomal abnormalitiesyou

major change

minor change

tiny change

large scale change

different amino acid

substituted amino acid

specific amino acids