Topic 6: Mutations

There are 2 types of mutationsThere are 2 types of mutations

ChromosomalChanges in structure

Or number of chromosomes

PointChanges in part of

DNA

Inheritable changes in DNA

Mutagenic AgentsMutagenic Agents• Mutations are caused by mutagenic agents. These include:

•Radiation (ie. X-rays, UV radiation, Microwave radiation)•Chemicals (for eg. chemicals in cigarette smoke, etc & also

the hepatitis virus can cause our immune system to produce mutagenic chemicals)

Mutagenic AgentsMutagenic Agents

Chromosomal MutationsChromosomal Mutations• Changes in structure and/or number of

chromosomes• Normal number of chromosomes in each human

cell is 46 (23 pairs and 2n = 46)These chromosomes are all taken from a 2n cell

KaryotypingKaryotyping• Chromosomes are organized according to 3

characteristics– Size, banding pattern, centromere position

• Used for detecting chromosomal abnormalities (mutations)

Sex?

Cells for karyotypyingChorionic Villus Sampling (CVS)

draws cells from outer membrane of embryo– CVS can be used as early

as 8 weeks of pregnancy

Ultrasound locates position of fetus

Amniocentesis uses a needle to withdraw some amniotic fluid from around fetus in the uterus.

How do we prepare a KaryotypeHow do we prepare a Karyotype• Blood is centrifuged to separate out blood cells• WBC’c are transferred & treated to stop cell division

– Which stage would we observe the cell? • Sample is fixed, stained and spread on a microscope

slide• Slide of 2n cells is examined • Chromosomes are photographed• Computers are used to arrange chromosomes into

pairs

Abnormal Meiosis• Chromosomal abnormalities result when

chromosomes and chromatids do not separate as they should during meiosis – This is called nondisjunction

• Nondisjunction can occur in 2 ways: 1. Anaphase I - homologous chromosomes move to the

same pole

2. Anaphase II – sister chromatids don’t separate and move to the same pole

In humans, diploid number is 46 and haploid number is 23.

46

46

24

22

24

24

22

22

23

23

24

22

23

23

Nondisjunction

Nondisjunction during Anaphase I Two gametes have an extra chromosome. Two gametes have one less chromosome.(All 4 cells are unhealthy)

Nondisjunction during Anaphase II One gamete has an extra chromosome. One gamete has one less chromosome(2 healthy cells, 2 unhealthy cells)

• Normal gametes have 23 chromosomes– Abnormal gametes form when there is either one more

(24) or one less (22)• Trisomy – three homologous chromosomes (47

chromosomes total)– Ex. Down’s Syndrome: trisomy of chromosome #21

• Monosomy – a single chromosome instead of a homologous pair (45 chromosomes in total)– Ex. Turner’s syndrome: monosomy of chromosome # 23

(XO)

Non-disjunction

23 from each46 total

Down Syndrome -Also known as trisomy 21 – 3 of chromosome 21 -47 chromosomes in each cell-1 in 800 babies have Down syndrome- Incidences increase as mothers age increases- Exposure to radiation results in increased chance of Down syndrome- Lower mental ability

-Down syndrome (DS) or Down's syndrome, also known as trisomy 21, is a genetic disorder caused by the presence of all or part of a third copy ofchromosome 21. It is typically associated with physical growth delays, characteristic facial features and mild to moderate intellectual disability. The average IQ of a young adult with Down syndrome is 50, equivalent to the mental age of an 8 or 9 year old child, but this varies widely.

Down SyndromeDown Syndrome• 2 #21 chromosomes fail to separate (they head to the

same pole) during anaphase I or II• Happens in production of one gamete …sperm or egg....not

both• One gamete ends up with 2 # 21’s

+3 #21’s

Down SyndromeDown SyndromeDid you know?It may take up to 45 years for the eggs in a woman to complete meiosis, whereas in a man the whole process takes only a few hours as sperm are being produced all the time. This difference can explain why the risk for a baby to have a chromosome anomaly increases with the mother's age, whereas the chance for a new alteration in the DNA sequence of a gene may relate more to the father's age.http://www.geneticseducation.nhs.uk/mededu/changes-to-dna-affect-gene-dosage-or-function/errors-during-meiosis

Klinefelter Syndrome - XXY

• Due to nondisjunction in the sperm or egg • one gamete contains 2 X’s, other contains only a Y (this is the normal one)• Male at birth, but sterile and produce female hormones• 1 in 10000 births

Turner’s Syndrome - XO

• Female only has 1 X chromosome • Due to nondisjunction during egg formation • One egg gets both X chromosomes, other egg gets no X chromosome • Cell without an X chromosome cannot survive

– This means that X contains genes necessary for life

1 in 10000 births

Jacobs Syndrome - XYY

• “Supermale” due to two Y chromosomes• Male, mostly normal• Sometimes excess acne, very tall

• Sometimes more aggressive

• Fragile X syndrome is the most commonly inherited form of mental retardation.

• Although it is thought to be an X-linked recessive trait with variable expression and incomplete penetrance, 30% of all carrier women are also affected.

• The syndrome is called “fragile-X” because there exists a fragile site or gap at the end of the long arm of the X-chromosome in lymphocytes of affected patients when grown in a folate deficient medium.

Fragile X SyndromeFragile X Syndrome

Effects of chromosomal changesEffects of chromosomal changes

Point MutationsPoint Mutations• Arise from mistakes in replication

which change the genetic code• An incorrect mRNA built using altered

DNA as template• Ribosome reads wrong code and builds

wrong protein using wrong amino acid• Most produce adverse effects but can

also be a source of genetic variability

Substitutions• When 1 or 2 bases have been

substituted for another one accidentally• Only one triplet on DNA affected

– Example if GGT changes to GCA– mRNA changes from CCA to CGU– Incorrect tRNA attracted into position

and wrong amino acid is placed in polypeptide chain

– Incorrect protein formed• Sickle cell anemia caused this way

Normal & Abnormal Red Blood Cells

Notice how a minor change in the DNAcauses a radical change in hemoglobin structure

Frameshift - Deletions• Often more severe consequences since a base is accidentally

dropped from the sequence• Many triplets in DNA sequence affected• Deletion alters the way the code is read• Like dropping a letter from a sentence!!!

Example: “Sometimes the error may arise” becomes “Someimest hee rrorm aya rise

Frameshift - Additions• A base is added to the DNA strand• Triplet with addition is affected and so are the rest of the

triplets afterwards• For example if DNA before mutation is

AAA TTT CCC GGG TTT CCC After addition new sequence would readAAA TTT GCC CGG GTT TCC

What’s added????

Examples of Point MutationsOriginal DNA Sequence

TAC GTT TCA GAG ACT

1. Original mRNA

aa

2. Substitution (change first G to C)

DNA

mRNA

aa

3. Addition of T before first A

DNA

mRNA

aa

4. Deletion of first G

DNA

mRNA

aa

AUG CAA AGU CUC UGA

Start glutamine

serine

leucine

stop

TAC CTT

TCA GAG

ACT

AUG GAA

AGU

CUC UGAStart glutamateserin

eleucine

stop

TTA CGT

TTC AGA

GAC

AAU GCA AAG

UCU CUGasp alanin

elysine serine leucin

eTAC TTT CA

GAGA

CT

AUG AAA GUC

UCU GAstart lysin

evaline

serine

Fun With Mutations!!!!! • Identify the mutation type...first strand is

unmutated...CCC TTT GCA GGA TTC......CCC TTA GCA GGA TTC...

• Identify the mutation type...first strand is unmutated

...GCT ATC TTC AAT CGA...

...GCT ATC TCA ATC GAT...

Substitution

Deletion

Variables Review

Controlled variables the component(s) or variable(s) the experimenter keeps the same

Manipulated variable the component or variable of the experiment we change or ‘manipulate’. The thing being tested

Responding variablethe component of the experiment we plan to measure (the results)

Controlled variables type of bacteria time temperature

Type of agar

Manipulated variable nicotine

Responding variable – growth of bacteria

1. A scientist wanted to see if nicotine causes cancer, so he exposed some bacterial cells growing on agar in a petri dish to nicotine and then tested to see if they had uncontrolled growth. He compared these cells to bacterial cells growing on agar in a petri dish that were not exposed to nicotine.