oht 02 mutations - macsciencemutations can alter the cell’s chemistry this may cause an observable...

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: [email protected]

AUSTRALIA:Biozone Learning Media AustraliaP.O. Box 7523 GCMC 4217 QLDTelephone: +61 (7) 5575-4615FAX: +61 (7) 5572-0161E-mail: [email protected]

UNITED KINGDOM:Biozone Learning Media (UK)P.O. Box 16710, Glasgow G12 9WSTelephone: +44 (141) 337-3355FAX: +44 (141) 337-2266E-mail: [email protected]

OHT 1Produced by:

BIOZONEINTERNATIONAL© 1993 – 2001

Printing onto Paper Prohibited

These masters may only be used to generateOverhead Transparenc ies (OHTs) .

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.

OHT 2Produced by:




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

OHT 3Produced by:




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

OHT 4Produced by:




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

OHT 5Produced by:




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:

OHT 6Produced by:




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.

OHT 7Produced by:




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.

OHT 8Produced by:




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

OHT 9Produced by:




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.

OHT 10Produced by:




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).

OHT 11Produced by:




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.

OHT 12Produced by:




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.

OHT 13Produced by:




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).

OHT 14Produced by:




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:

OHT 15Produced by:




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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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.

OHT 17Produced by:




Set 2: Mutations

Cystic Fibrosis


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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Set 2: M

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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.

OHT 19Produced by:




Set 2: Mutations

ß-Thalassaemia


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.

OHT 20Produced by:




Set 2: Mutations

Huntington Disease


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).

OHT 21Produced by:




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.

OHT 22Produced by:




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.

OHT 23Produced by:




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.

OHT 24Produced by:




Set 2: Mutations

MNOPQRST

SegmentRemoved

ABCDEFGH

MNOPQRST

GH

MNOPQRST

GH

ABCDEF1

234

567890

1234

567890

ABCDEF

1234

567890

Segmentsjoin

Break

Genes


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

OHT 25Produced by:




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.

OHT 26Produced by:




Set 2: Mutations

CDEF

AB

GH

MNOPQRST

ABCDEFGH

MNOPQRST

ABFEDCGH

MNOPQRST

SegmentRotates 180°

Segmentrejoins

Break

Genes


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.

OHT 27Produced by:




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).

OHT 28Produced by:




Set 2: Mutations

MNOPQ

Segmentremoved

ABCDEF

MNOPQ

F

ABCDE

ABCDEF

MNOPQ

ABCDEABCDEF

MNOPQ

ABCDEF

MNOPQ

Joins ontoHomologouschromosome

MNOPQ

FBreak

Genes


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.

OHT 29Produced by:




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.

OHT 30Produced by:




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).

OHT 31Produced by:




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

OHT 32Produced by:




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

OHT 33Produced by:




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

OHT 34Produced by:




Set 2: Mutations

Patau SyndromeChromosome affected: Trisomy 13

Incidence rate of 1 in 3,000 livebirths (with a maternal age effect).

OHT 35Produced by:




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:




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:




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:




Set 2: Mutations

20 25 30 35 40 45 500

10

20

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40

50

60

70

80

90

Est

imat

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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:




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

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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:




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:

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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:




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:




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:




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:




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:




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:




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

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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:




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:




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:




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:




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

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oht 02 mutations - macsciencemutations can alter the cell’s chemistry this may cause an observable...

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