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Mutations
Presentation MEDIA: Genetics & Evolution Series
Set No. 2
1 Mutations
2 Causes of Mutations
3 Effects of Mutagens
4 Rates of Mutation
5 Human Mutation Rates
6 Location of Mutations
7 The Effects of Mutations
8 Types of Mutations
9 Single Gene Mutations
10 Point Mutations: Missense Substitution
11 Point Mutations: Nonsense Substitution
12 Point Mutations: Reading Frame Shift by Insertion
13 Point Mutations: Partial Reading Frame Shift
14 Tautomerism
15 Sickle Cell Disease
16 Sickle Cell Mutation
17 Cystic Fibrosis
18 Cystic Fibrosis Mutation
19 ß-Thalassaemia
20 Huntington Disease
21 Block Mutations
22 Block Mutations: Deletion
23 Deletion on Human Chromosome 1
24 Block Mutations: Translocation
25 Translocation on Human Chromosomes 9 & 22
26 Block mutations: Inversion
27 Inversion on Human Chromosome 2
28 Block Mutations: Duplication
29 Duplication on Human Chromosome 9
30 Aneuploidy
31 Down Syndrome
32 Causes of Down Syndrome
33 Down Syndrome Phenotype
34 Patau Syndrome
35 Patau Syndrome Phenotype
36 Edward Syndrome
37 Edward Syndrome Phenotype
38 Maternal Age Effect in Aneuploidy
39 Causes of Maternal Age Effect
40 The Fate of Conceptions
41 Aneuploidy in Human Sex Chromosomes
42 Human Sex Aneuploidy Phenotypes
43 Faulty Sperm Production
44 Faulty Egg Production
45 Klinefelter Syndrome
46 Turner Syndrome
47 Polyploidy
48 Polyploidy in Humans
49 Autopolyploidy
50 Allopolyploidy
51 The Evolution of Wheat
52 Mutations: Overview
53 Evolutionary Significance of Mutations
OHT Title OHT Title
Index to OHT Titles
Set 2: Mutations
© 1993-2001 Biozone International Ltd ISBN 0-909031-41-X
Presentation MEDIA
NEW ZEALAND:Biozone International LtdP.O. Box 13-034 HamiltonTelephone: +64 (7) 856-8104FAX: +64 (7) 856-9243E-mail: info@biozone.co.nz
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UNITED KINGDOM:Biozone Learning Media (UK)P.O. Box 16710, Glasgow G12 9WSTelephone: +44 (141) 337-3355FAX: +44 (141) 337-2266E-mail: info@biozone.co.uk
OHT 1Produced by:
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Set 2: Mutations
Chromosome
Cell
Nucleus
Mutation
Mutations can alterthe cell’s chemistry
This may cause anobservable changein the organism’s:
• physiology• anatomy• behaviour
MutationsMutations are alterations in the DNA of chromosomes.
Many mutations may be neutral or 'silent' (i.e. they haveno observable effect on the organism).
Harmful mutations become evident because they mayalter the survival capacity of the organism.
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Set 2: Mutations
Causes of MutationsMutations may occur randomly and spontaneously.
They may also be induced by environmental factors.
Spontaneous Mutations
– Arise from errors in replication– Different genes mutate at different rates
Induced Mutations
Mutations can be induced by mutagens (environmentalfactors that cause a change in DNA):
Examples: – radiation (e.g. UV rays)– viruses– microorganisms– Environmental poisons and irritants– Alcohol and diet
The Effect of Mutagens on DNA
After exposure to UV light, a potentmutagen, adjacent thymine basesin DNA become cross-linked toform a 'thymine dimer'.
This disrupts the normal basepairing and throws the controllinggene's instructions into chaos.
UV Light
Thymine dimer
DNA of tumoursuppressor gene
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Set 2: Mutations
Effects of MutagensEffectsType of Mutagen Those Most at Risk
Diets high in fat, slow thepassage of food through thegut giving time for mutagenicirritants to form. High alcoholintake increases the risk ofsome cancers.
• Those with a diet high in totalfats.
• There may be familial(inherited) susceptibility.
• Risks may be compounded byother lifestyle choices e.g.smoking.
Many chemicals aremutagenic. Synthetic andnatural examples include:organic solvents (e.g.benzene), asbestos, tobaccotar, vinyl chlorides, and nitrites.
• Chemical industry workers,including the glue, paint,rubber, resin, and leatherindustries.
• Smokers.
• Coal and other mining workers.
• Exposure to petroleum volatilesand vehicle exhaust emissions.
Some viruses integrate into thehuman chromosome, upsettinggenes and triggering cancers.
• Hepatitis B: Intravenous drugusers.
• HIV: Intravenous drug users,those with unsafe sexualactivity (i.e. unprotected sexwith new partners).
Nuclear and ultravioletradiation, X-rays and gammarays. Ionising radiation isassociated with thedevelopment of cancers.
• Those working withradioisotopes.
• Living near nuclear plants, wastedumps, or testing sites.
• Fair skinned people in tropicalregions and sub tropical areas.
• Excess use of tanning beds.
Alcohol and Diet
EnvironmentalPoisons
Viruses andMicroorganisms
Ionising Radiation
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Set 2: Mutations
Rates of MutationGenes mutate at known rates, but the rate variesdepending on the gene involved - some genes havehigh spontaneous mutation rates.
Calculation of the average number of mutant genes ina human:
1. There are thought to be about 100,000 genesmaking up the human genome.
2. Since there are two copies of each gene (onhomologous chromosomes), each cell has a totalof 200,000 genes.
3. In higher organisms, a mutation for a specificgene will occur in one gamete in 300,000.
4. Then each of us on average:
carries about 1 new mutant gene!
Rates of mutation for different genes within a singlespecies are probably similar, but the viability ofmutations varies greatly.
2 x 105 ÷ 3 x 10-5 = 0.67
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Set 2: Mutations
Human Mutation Rates
mutations permillion gametesper generation
Retinoblastoma Dominant 15-23Produces a tumour in the eye
Tay-Sachs disease Recessive 11Produces blindness, paralysis,mental deficiency, death, withonset at about 6 years of age
Haemophilia Sex-linked 25-32Produces uncontrollablebleeding due to an inabilityof the blood to clot
Muscular Dystrophy Sex-linked 43-100Produces progressivewasting of muscles andeventual death
Albinism Recessive 28Production of melaninaffected, resulting in lack ofpigment in skin, eyes, and hair
All genes causing deathbefore early adulthood: 40,000
Examples of human genes with known mutation ratesare listed below:
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Set 2: Mutations
Somatic Mutations occur in bodycells – they are not inherited but mayaffect the person during their lifetime
Gametic Mutations are inheritedand occur in the testes of males
and the ovaries of females
Fertilisation
Cleavage.Prior to implantation
Foetus
Baby
Cells of tissuesaffected by themutation
Egg
SpermaaaEgg
SpermMutation
Gametic Mutations Somatic MutationsaMutation
Location of MutationsThe location of a mutation determines whether or not itwill be inherited.
Most mutations occur in somatic (body) cells and arenot inherited (not involved in reproduction).
Gametic mutations occur in the cells of gonads (spermand eggs) and may be inherited.
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Set 2: Mutations
The Effects of MutationsHarmful Mutations: There are many examples of harmful mutations that result from alterations to the DNA base sequence.
Examples include:
– Sickle-cell disease
– Cystic fibrosis– Thalassemias
These mutations are harmful because they alter the DNAsequence, thereby upsetting the structure and function of theprotein they code for.
Neutral Mutations: Because these often produce little or no change in the phenotype, neutral mutations are hard to detect.
They may have little or no effect on the survival of anorganism or its ability to reproduce.
May be the result of a ‘same-sense’ mutation where achange in the third base sequence still codes for the sameamino acid.
Beneficial Mutations: Beneficial mutations are best observed in species with short generation times.
Examples include:– Bacterial resistance to antibiotics.
– Insecticide (e.g. DDT) resistance in insect pests.
– Rapid mutation rates in the protein coats of viruses.
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Set 2: Mutations
Types of MutationsSingle Gene Mutations
Genetic change affectingthe base sequence of asingle gene.
May result in theformation of a new allele.
Chromosome Rearrangements(Block mutations)
Change in the structure of achromosome involving largepieces being rearranged.
Whole groups of genes areaffected.
Changes in Chromosome Number
Aneuploidy: Loss or gain ofwhole chromosomes.
Polyploidy: Loss or gain ofcomplete sets of chromosomes.
Mutation: Substitute T instead of C
MutantDNA
OriginalDNA
21
Break Break
Chromosomesegment is lost
C D E F
A B M N O P Q R S TG H
Genes
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Set 2: Mutations
Original Unaltered Code
OriginalDNA
mRNA
AminoAcids
Translation
Amino acid sequence forms a normal polypeptide chain
Transcription
Phe Tyr Glu Val LeuGlu
Single Gene MutationsPoint mutations change the sequence of bases in DNAfor a single gene and may produce a new allele of a gene.
Single gene mutations involving a single nucleotide areusually called point mutations.
The new DNA sequence will result in a new sequence ofamino acids making up a protein.
Because of the degeneracy in the genetic code not allchanges in a DNA sequence will result in a new sequenceof amino acids.
Even with a change in amino acid sequence, proteinfunction may not be affected.
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Set 2: Mutations
Polypeptide chain with wrong amino acid
Mutation: Substitute T instead of C
Phe Tyr Lys Glu Val Leu
MutantDNA
OriginalDNA
mRNA
AminoAcids
Single Gene Mutations:Missense Substitution
A single base is substituted by another.
This usually results in coding for a new amino acid inthe polypeptide chain.
If the third base in a triplet had been substituted, theresulting amino acid may not be altered (due todegeneracy in the code).
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Set 2: Mutations
Mutated DNA creates a STOP codon whichprematurely ends synthesis of the polypeptide chain
Mutation: Substitute A instead of C
Phe Tyr
MutantDNA
OriginalDNA
mRNA
AminoAcids
Single Gene Mutations:Nonsense Substitution
A single base is substituted by another.
This results in a new triplet that does not code for anamino acid.
The resulting triplet may be an instruction to terminatethe synthesis of the polypeptide chain.
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Set 2: Mutations
MutantDNA
OriginalDNA
mRNA
AminoAcids
Mutation: Insertion of C
Phe Tyr Gly Arg Gly Ser
Large scale frame shift resulting in a completely new sequence of aminoacids – the resulting protein is unlikely to have any biological activity
Single Gene Mutations:Reading Frame Shift by Insertion
A single base is inserted, upsetting the readingsequence for all those after it.
This results in new amino acids in the polypeptide chainfrom the point of insertion onwards.
The resulting protein will be grossly different from theone originally coded for (therefore non-functional).
This type of reading frame shift can also be causedby a base deletion.
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Set 2: Mutations
MutantDNA
OriginalDNA
mRNA
AminoAcids
Altered chain which may or may not produce a protein with biological activity
Mutation: Deletion of C
Phe Val Arg Lys Val Leu
Mutation: Insertion of C
Single Gene Mutations:Partial Reading Frame Shift
A single base is inserted and another is deleted at adifferent location, resulting in a localised frame shift.
This results in a new amino acid sequence betweenthese points in the polypeptide chain.
Depending on how many amino acids are affected, theresulting protein may have some useful function(biological activity).
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Set 2: Mutations
Usual basecombinations
Abnormal basecombinations
AbnormalGuanine
Thymine
TG
Guanine Cytosine
G C
AbnormalAdenine
Cytosine
CA
Adenine Thymine
A T
AbnormalThymine
Guanine
GT
Thymine Adenine
T A
AC
AbnormalCytosine
Adenine
Abnormalpartner
Abnormalbase
C G
Cytosine Guanine
Normalbase
Normalpartner
Hydrogen bonds
TautomerismSome point mutations may result from bases with anunusual number of hydrogen-bonding sites.
Results in mismatching of base pairs.
Irregular base configurations are called tautomers andare indicated by abnormal base combinations below:
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Set 2: Mutations
Symptoms:Include the following:
• Pain, ranging from mild to severe, inthe chest, joints, back, or abdomen
• Swollen hands and feet
• Jaundice
• Repeated infections, particularlypneumonia or meningitis
• Kidney failure
• Gallstones (at an early age)
• Strokes (at an early age)
• Anaemia.
Gene Location: Chromosome 11
qpHBB
Sickle Cell DiseaseSynonym: Sickle cell anaemia
Incidence: Most common in people of African ancestry.
West Africans: 1% (10-45% are carriers)
West Indians: 0.5%
Gene Type: Autosomal recessive mutation which resultsin the substitution of a single nucleotide in the HBB genethat codes for the beta chain of haemoglobin.
OHT16
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Set 2: M
utatio
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Chromosome 11β-Chain
Haemoglobin
Haemoglobin moleculesare made up of 2 α-chainsand 2 β-chains linked together
Haemoglobin clustered together toform fibres that deform the red bloodcells into a sickle shape
The sickle cell mutationinvolves the substitution ofone base for another in theHBB gene, causing a singleamino acid to be altered.
First base
Codes for the 1st amino acid
Normal base: TSubstituted base: A
DNA
p
q
HBBgene
Normal Red Blood Cellscontaining normal
haemoglobin (soluble)
Sickle Cellscontaining mutant
haemoglobin (less soluble)
Alpha (α) chainBeta (β) chain
Sickle Cell MutationThe mutation responsible for causing sickle cell disease is apoint substitution mutation.
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Set 2: Mutations
Cystic Fibrosis
Gene Location: Chromosome 7
qpCFTR
Symptoms:• infertility occurs in males and
females.
Disruption of the following glands:
• the pancreas
• intestinal glands
• biliary tree (biliary cirrhosis)
• bronchial glands (chronic lunginfections)
• sweat glands (high salt contentof which becomes depleted in ahot environment)
Synonyms: Mucoviscidosis, CF
Incidence: Varies with populations:
Asians: 1 in 10,000; Caucasians: 1 in 20-28 are carriers
Gene Type: Autosomal recessive. Over 500 differentrecessive mutations (deletions, missense, nonsense,terminator codon) of the CFTR gene have been identified.
OHT18
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s (O
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Set 2: M
utatio
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Normal CFTR Proteincorrectly controls chloride ion
balance in the cell
Mutant CFTR Proteinallows chloride ions to remain in the cell
and leads to water entering the cell
CellMembrane
Chromosome 7
Cl-
Cellcytoplasm
Outsidethe cell
Cl-Cl-
Cl-
Cellcytoplasm
Outsidethe cell
Cl-Cl-
Cl-
Cl-Cl-Cl-
Cl-Water
DNA
Base 1630
This triplet codes forthe 500th amino acid
The 508th triplet is lost (notpresent) in the mutant form
CFTR Protein
p
q
CFTRgene
Cystic Fibrosis MutationThe mutation responsible for causing most cases ofcystic fibrosis is a single gene deletion mutation.
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Set 2: Mutations
ß-Thalassaemia
Gene Location: Chromosome 11
Symptoms:• The result of haemoglobin with
few or no beta chains, causes asevere anaemia during the firstfew years of life.
• People with this condition aretired and pale because notenough oxygen reaches the cells.
qpHBB
Synonyms: Cooley anaemia, Mediterranean anaemia
Incidence: Most common type of thalassaemiaaffecting 1% of some populations. More common inAsia, Middle East and Mediterranean.
Gene Type: Autosomal recessive mutation of the HBBgene coding for the haemoglobin beta chain.
It may arise through a gene deletion or a nucleotidedeletion or insertion.
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Set 2: Mutations
Huntington Disease
Gene Location: Chromosome 4
Symptoms:• Mutant gene forms defective
protein: Huntingtin.
• Progressive, selective nerve celldeath associated with chorea(jerky, involuntary movements)
• Psychiatric disorders
• Dementia (memory loss,disorientation, impaired ability toreason, and personality changes).
qpIT15
Synonym: Huntington’s chorea, HD (abbreviated)
Incidence: An uncommon genetic disease present in 1 in20,000 people.
Gene: An autosomal dominant mutation of the HD gene(IT15) caused by an increase in the length (36-125) of aCAG repeat region (normal range is 11-30 repeats).
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Set 2: Mutations
Block MutationsCauses of Block Mutations
Some can result from errors in the crossing overprocess during meiosis.
Mutagens (e.g. X-rays) may cause some forms ofblock mutation.
Block mutations cause genetic imbalances that usuallydisrupt the development of an organism.
Types Fate of Chromosome Fragments
Inversion Pieces of chromosome are flipped upsidedown so the genes appear in the reverse order.
Translocation Pieces of chromosome are moved from onechromosome into another.
Duplication Pieces of chromosome are repeated so thereare duplicate segments.
Deletion Pieces of chromosome are lost.
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Set 2: Mutations
CDEF
AB
GH
MNOPQRST
Segmentis lost
ABGH
MNOPQRST
Chromosomerejoins
ABCDEFGH
MNOPQRST
Break
Break
Genes
Step 1 Step 2 Step 3
Block Mutations: DeletionBreak occurs at two points on the chromosomeand the middle piece falls out.
The two ends then rejoin to form a chromosomedeficient in some genes.
Alternatively, the end of a chromosome maybreak off and be lost.
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Set 2: Mutations
Mid-Segment DeletionTip Deletion
Lost
1
1
Before After
1
Lost
1
Tiprejoins
Before After
Deletion onHuman Chromosome 1
Human chromosome 1 shows two forms of deletion.
These may involve deletion of either a chromosome tip(left) or a middle segment with the tip rejoined (right).
This loss of genetic material may be harmful.
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Set 2: Mutations
MNOPQRST
SegmentRemoved
ABCDEFGH
MNOPQRST
GH
MNOPQRST
GH
ABCDEF1
234
567890
1234
567890
ABCDEF
1234
567890
Segmentsjoin
Break
Genes
Step 1 Step 2 Step 3
Block Mutations: TranslocationTranslocation involves the movement of a group ofgenes between different chromosomes.
A piece of one chromosome breaks off and joinsonto another chromosome.
Consequence: A chromosome deficient in genes.
The large chromosome (green) and the small chromosome (dark blue) are not homologous
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Set 2: Mutations
Before Translocation After Translocation
The tips of thechromosomes swap
9
22
9
22
Translocation onHuman Chromosomes 9 & 22
Translocation can occur between humanchromosomes 9 and 22.
The tips of the two chromosomes are exchanged.
This is the translocation observed in chronicmyeloid leukaemia.
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Set 2: Mutations
CDEF
AB
GH
MNOPQRST
ABCDEFGH
MNOPQRST
ABFEDCGH
MNOPQRST
SegmentRotates 180°
Segmentrejoins
Break
Genes
Step 1 Step 2 Step 3
Break
Block Mutations: Inversion
The middle piece of the chromosome falls outand rotates through 180° and then rejoins.
There is no loss of genetic material.
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Set 2: Mutations
Normal Inversion
Flip
2 2
Inversion onHuman Chromosome 2
A segment of chromosome 2 is inverted(caused by looping of the chromosome).
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Set 2: Mutations
MNOPQ
Segmentremoved
ABCDEF
MNOPQ
F
ABCDE
ABCDEF
MNOPQ
ABCDEABCDEF
MNOPQ
ABCDEF
MNOPQ
Joins ontoHomologouschromosome
MNOPQ
FBreak
Genes
Step 1 Step 2 Step 3
Block Mutations: DuplicationA segment is lost from one chromosome and isadded to its homologue.
The chromosome on the left (below) was the'donor' of the duplicated piece of chromosome.
The chromosome with the duplication will becomeincorporated into a gamete, which may latercontribute to an embryo.
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Set 2: Mutations
9
Normal
9
Identicalsegment
Duplication
Duplicatesegment
A segment is tansferredfrom one chromosome
into its homologue
Duplication onHuman Chromosome 9
A segment of chromosome 9 is duplicated.
A segment is taken from its homologue andinserted to produce double copies of some genes.
Some genes may be disrupted by this process.
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Set 2: Mutations
AneuploidyThe normal condition for a body cell is forchromosomes to be present as homologous pairs(a condition known as disomy).
Aneuploidy is a condition where one or morechromosomes are missing from or added to thenormal body cell chromosome number.
Examples: Nullisomy 0 homologues
Monosomy 1 homologue
Trisomy 3 homologues
Tetrasomy 4 homologues
May involve autosomes – examples are:
Down Syndrome: Chromosome 21Edward Syndrome: Chromosome 18Patau Syndrome: Chromosome 13
May involve sex chromosomes – examples are:
Klinefelter Syndrome: XXY
Turner Syndrome: XO
Why are they called syndromes?
When a disease causes multiple effects it is calleda syndrome (virtually all chromosomeabnormalities are in this category).
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Set 2: Mutations
Down SyndromeChromosome affected: Trisomy 21
Incidence rate of 1 in 800 births in women giving birthat 30 to 31 years of age (this is the most commonform of aneuploidy in humans).
The young boy below shows the typical appearanceof Down Syndrome:
Art
Toda
y.co
m
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Set 2: Mutations
There are three causes of Down syndrome, eachproducing a different severity of the syndrome:
92% of all cases result from non-disjunction ofchromosome 21 during meiosis (see thekaryotype shown below).
5% result from translocation of chromosome 21(usually onto chromosome 14).
3% arise from a failure during mitosis (non-disjunction of chromosome 21) in a cell of avery early embryo – the resulting individual is a‘mosaic’ of normal and Down syndrome cells.
Causes of Down Syndrome
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Set 2: Mutations
Down Syndrome PhenotypeThe expression of traits in the Down syndromephenotype varies greatly, depending on which of thethree chromosome abnormalities caused it.
The most common phenotypic traits are:
1. Skin fold over the eye.
2. Reduced mental capacity (varies greatly).
3. Short stature, stubby fingers, heart defects.
Slanting eyesEpicanthic eyefold
Abnormal ears
Many “loops”on finger tipsPalm creases
Special skinridge patterns
Absence of one rib onone or both sides
Umbilical hernia
Abnormal pelvis
Poor muscle tone
Enlarged colon
Intestinal blockage
Back of head flatBroad flat faceShort nose
Short and broad hands
Small and arched palateBig wrinkled tongueDental anomalies
Congenitalheart disease
Big toeswidelyspaced
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These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Patau SyndromeChromosome affected: Trisomy 13
Incidence rate of 1 in 3,000 livebirths (with a maternal age effect).
OHT 35Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Patau Syndrome Phenotype
Phenotype of an Patau syndrome child:
1. Multiple defects (see below).
2. Usually death by age 1 to 3 months.
Cleft palateand hare lip
Polydactyly(extra finger)
Structural eye defectsFaulty retinaSmall eyes
Abnormal palm pattern
Low set ears
Small headScalp defects
Polydactyly(extra toe)
Heart defects
Spinal defects(meningomyelocele)
OHT 36Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Edward SyndromeChromosome affected: Trisomy 18
Incidence rate of 1 in 5,000 live births(with a maternal age effect).
OHT 37Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Edward Syndrome PhenotypePhenotype of an Edward syndrome child:
1. Ear deformities.
2. Heart defects.
3. Spasticity and other defects.
4. Usually death by age 1 year.
Small mouth andunusually small jaw
A small head(microcephaly)
Low setmalformed ears
Clenched fists withcharacteristic overlappingindex fingerNails are
underdeveloped
Big toe isshortened andfrequently bentbackward
Underdevelopedor absent thumbs
Club feet
Congenital anomaliesof the lung, kidneysand ureters
Redundant skin folds,especially over theback of the neck
Small chest
OHT 38Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
20 25 30 35 40 45 500
10
20
30
40
50
60
70
80
90
Est
imat
ed R
ate
of
Do
wn
Syn
dro
me
(per
100
0 bi
rths
)
Maternal Age
1 in 2,300 1 in 880 1 in 290
1 in 100
1 in 46Incidence per
1000 Live Births< 11 - 22 - 55 - 1010 - 20
Maternal Age(years)< 30
30 - 3435 - 3940 - 44
> 44
Maternal Age Effectin Aneuploidy
Many aneuploidies show a ‘maternal age effect’,with incidence increasing with age of the mother.
Example: Down syndrome is 100 times morelikely in children of mothers over 45 years, than inthose of mothers less than 19 years.
OHT 39Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Old egg cellsare prone tofaulty meiosis
Sperm from older men havea slight tendency to bedeficient in chromosomes
Causes of Maternal Age EffectMaternal age effect probably arises because:
1. All eggs are present at birth but are suspended in theirdevelopment in early prophase until puberty.
2. A woman, on average, will produce about 400 eggs inher lifetime (12 per year).
3. Therefore, by the end of her reproductive life, the eggcells that remain are old and there is a greater chancethat errors in meiosis will occur.
A similar, though less marked effect is exerted bythe age of the father.
OHT40
Produced by:
BIO
ZO
NE
INT
ER
NA
TIO
NA
L©
1993 – 2001
Prin
ting
on
to P
ap
er P
roh
ibite
d
Th
es
e m
as
ters
ma
y o
nly
be
us
ed
to g
en
era
teO
ve
rhe
ad
Tra
ns
pa
ren
cie
s (O
HT
s).
Set 2: M
utatio
ns
Spontaneous Miscarriages150,000
Live Births850,000
Sex ChromosomeAneuploids
Male ............ 1,427
Female ........... 422
ChromosomeAbnormalities
75,000
Perinatal Deaths17,000
AutosomalTrisomics
Trisomy 13 ........... 42Trisomy 18 ......... 100Trisomy 21 ...... 1,041
Children833,000
Other Causes75,000
With Chromosome Abnormalities5,165
OtherAbnormalities
Total ............ 2,133
Conceptions1,000,000
Trisomics ............. 39,000
XO ....................... 13,500
Triploids ............... 12,750
Tetraploids ............. 4,500
Others ................... 5,250
The Fate of ConceptionsFor every million conceptions that occur, a significant number havegenetic abnormalities and fail to develop into a completely normal child.
OHT 41Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
SexChromosomes
ApparentSex
Phenotype
* These apparent males and females appear to have the wrongsex chromosome complement. this is due to hormonaldeficiencies or developmental errors.
Male Down-like syndrome, very retardedX X X X Y
Male Extreme Klinefelter, mentally retardedX X X Y
Male Resembles Klinefelter, sterileX X Y Y
Male Klinefelter syndromeX X Y
Male Jacob syndrome, apparently normal male, tall, aggressiveX Y Y
Male* Short, broad chested, sterile, hypogonadismX X
Male Normal maleX Y
? Not Known (non-viable)Y O
Female Rather like Down syndrome, low fertility/intelligenceX X X X X
Female Rather like Down syndrome, low fertility/intelligenceX X X X
Female Apparently normal female, greater tendency to criminalityX X X
Female* No pubertal developmentX Y
Female Normal FemaleX X
Female Turner syndromeX O
Aneuploidy inHuman Sex ChromosomesThe normal complement for human sex chromosomes is:
Male: XYFemale: XX
Unusual sex chromosome configurations can arise frommistakes made during gamete formation (failure of sexchromosomes to separate properly during meiosis).
OHT42
Produced by:
BIO
ZO
NE
INT
ER
NA
TIO
NA
L©
1993 – 2001
Prin
ting
on
to P
ap
er P
roh
ibite
d
Th
es
e m
as
ters
ma
y o
nly
be
us
ed
to g
en
era
teO
ve
rhe
ad
Tra
ns
pa
ren
cie
s (O
HT
s).
Set 2: M
utatio
ns
TurnerSyndrome
NormalFemale
NormalMale
KlinefelterSyndrome
JacobSyndrome
SuperFemale
XY XYY,XYYY
XXY, XXXY,XXXXY
XO XXX, XXXX,XXXXX
XX
Human Sex Aneuploidy PhenotypesFour phenotypes of people with abnormal numbers of sexchromosomes (together with the normal male and female ones):
OHT 43Produced by:
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Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
KlinefelterSyndrome
TurnerSyndrome
Offspring
Mistakeduringmeiosis
Male
XXY
Female
X
Primaryspermatocyte
Faulty gametes
XY
XXY XO XXY XO
XYXY XXXX
KlinefelterSyndrome
TurnerSyndrome
XX
Faulty Sperm ProductionAneuploidy in human sex chromosomes may resultfrom faulty sperm production.
Results from failure of the X and Y chromosomes toseparate during meiosis.
OHT 44Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
FemaleMale
XXY XO YOXXX
X
XY XX
XXY
X X Y Y XX XX
SuperFemale
TurnerSyndrome
Not viable
Mistakeduringmeiosis
Primaryoocyte
KlinefelterSyndrome
Offspring
Faultygametes
Faulty Egg ProductionAneuploidy in human sex chromosomes mayresult from faulty egg production.
Results from failure of the two X chromosomesto separate during meiosis.
OHT 45Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Klinefelter SyndromeChromosome complement: 44 + XXY
Karyotype and phenotype:
Mildly impaired IQ(intelligence)
Chest hairis sparse
Penis and testesunderdeveloped, lowlevels of testosterone.Always infertile.
Limbs tend to belonger than average
Frequently some breastdevelopment (low levelsof testosterone)
Poor beard growth
Osteoporosis
Female type publichair pattern
OHT 46Produced by:
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Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Turner SyndromeChromosome complement: 44 + XO
Karyotype and phenotype:
Characteristicresidual lateralweb neck
Degenerate ovaries -almost always infertile
Reduced stature - body istypically short
Constriction of aorta
Low posterior hair line
Puffy fingerswith deep set,hyperconvexfinger nails
Mental development normal,difficulty with spatial memory
Elbowdeformity
Poor breasts development
brown spots (nevi)
OHT 47Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
PolyploidyAn organism that has three or more complete sets ofchromosomes (3N or greater).
Types of Polyploidy:
Autopolyploid: A polyploid involving the duplication ofchromosomes from a single species.
Allopolyploid: A polyploid involving the duplication ofchromosomes in a hybrid between two species.
Amphiploid: Describes the result of the last stage ofallopolyploidy where a (usually) fertile hybrid is formedby doubling of chromosomes in a hybrid.
Polyploidy is common in plants because vegetativegrowth can produce numerous individuals with thesame chromosome type/number.
Name Number Name Number
Common wheat ........6N = 42 Banana ...................3N = 27
Tobacco ....................4N = 48 Boysenberry ...........7N = 49
Potato .......................4N = 48 Strawberry ..............8N = 56
Many ferns are polyploid with chromosome number up to 400N
Examples of Polyploid Plants
OHT 48Produced by:
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These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Polyploidy in HumansPolyploidy is rarely observed in humans, but it isthought to be one of the more common causes ofspontaneous abortion.
The example below shows a triploidy (3N = 69)condition found in a baby that went to term (9months gestation) and then died at birth.
The phenotype of this individual is unknown.
OHT49
Produced by:
BIO
ZO
NE
INT
ER
NA
TIO
NA
L©
1993 – 2001
Prin
ting
on
to P
ap
er P
roh
ibite
d
Th
es
e m
as
ters
ma
y o
nly
be
us
ed
to g
en
era
teO
ve
rhe
ad
Tra
ns
pa
ren
cie
s (O
HT
s).
Set 2: M
utatio
ns
BBB
BB
Sterilehybrid
Normalhaploidgamete
DiploidgameteB
SameSpecies
BB
BB AA
AAAA
AA
DiploidgametesAA
Fertilehybrid
SameSpecies
AA
AutopolyploidyAutopolyploidy is a type of polyploidy.
It involves a multiple of identical sets of chromosomes from the same species.
Hybrid may be fertile or sterile, depending on the number of chromosome sets.
Hybrids with an even number of homologous chromosome sets (e.g. 4, 6, 8...28)will be fertile because chromosome pairing can occur at meiosis.
OHT 50Produced by:
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Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
AllopolyploidyAllopolyploidy is a type of polyploidy.
It involves the combination of chromosomes fromtwo or more different species, to form a hybrid.
Fertile polyploids may arise from doubling of thechromosome complement in the infertile hybrid(a process called amphiploidy).
Many commercial plant varieties, being hybrids,are polyploids of this type.
AB Diploid gametesfrom identicalinfertile hybrids.
(in flowering plants, thiscould be self pollination)A
mp
hip
loid
y
Haploidgametes
Fertileallotetraploid
Species A Species B
Species C
Infertilehybrid
AA BB
AB
AB
AABB
BA
OHT 51Produced by:
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Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Interbreedto formsterilehybrid
Domesticated inthe Middle East
Interbreedto formsterilehybrid
Amphiploidy doubleschromosome number andcreates fertile hybrid
Amphiploidy doubleschromosome numberand creates fertile hybrid
X
X
Wild Einkorn
Genome:
2N No.
AA
14
SterileHybrid
AB
2N No. 14
SterileHybrid
ABD
2N No. 21
Einkorn
Genome:
2N No.
AA
14
Wild Grass
Genome:
2N No.
BB
14
Emmer Wheat
Genome:
2N No.
AABB
28
Goat Grass
Genome:
2N No.
DD
14
Common Wheat
Genome:
2N No.
AABBDD
42
The Evolution of WheatThe common wheat has developed as a result ofseveral polyploid events after the formation ofhybrids between different grass species:
OHT 52Produced by:
BIOZONEINTERNATIONAL© 1993 – 2001
Printing onto Paper Prohibited
These masters may only be used to generateOverhead Transparenc ies (OHTs) .
Set 2: Mutations
Mutations: OverviewAll new alleles originate by mutation.
New alleles introduce genetic variation uponwhich natural selection can act.
Most mutations occur in somatic cells andare not inherited.
Only mutations in gametes can be inherited.
Fitness describes the value of a mutation to the survivaland reproductive success of the organism. A mutationmay turn out to be:
1. Lethal MutationMany mutations are lethal and embryos are non-viable (causing spontaneous abortions).
2. Harmful Mutation Non-lethal mutations may be expressed as effects
that lower survival or reproductive capacity.
e.g. Down syndrome; sickle cell disease.
3. Silent or Neutral MutationMost point mutations are probably harmless, withno noticeable effect on the phenotype.
4. Useful Mutation Occasionally mutations may occur which are useful,
particularly in a new environment.
e.g. DDT resistance in insects,antibiotic resistance in bacteria.
Fitness of Mutations
OHT 53Produced by:
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Set 2: Mutations
Evolutionary Significance of Mutations
The role of chromosomal aberrations in speciation:
Polyploidy can result in the formation of “instant species”by creating a barrier to chromosome pairing at meiosis(common in plants).
Fusion of chromosomes (a form of translocation) mayresult in a reduction in chromosome number – resultingin reproductive isolation and therefore a new species.
Example: Fusion of chromosomes may have taken placeduring the course of human evolution.
The chromosome number in the great apes is 2N = 48,whereas in humans 2N = 46.
Possible fusion oftwo chromosomesto create the No. 2chromosome inhumans.
Note the similarbanding patterns ofchromosomes fromrelated primatespecies.
Human Chimpanzee Gorilla Orangutan
2
13 11 11
12 12 12
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