Download 3-5 mutations F11

Mutations
Mutations in DNA can alter cells
Mutations:
What is a mutation?

Any change in the nucleotide sequence of
DNA
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Here a single base is changed:
2 general ways to alter DNA

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Change a single DNA base
Or entire sections of DNA can move from one
place to another
Misspelling
Changes in a single DNA base

A small change can make a
BIG difference
Caused by errors in DNA replication, UV
radiation, or chemical carcinogens
Normal Hb
Mutant Hb


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A change in a single nucleotide in the gene for
hemoglobin
A change in a single amino acid
A change in the shape of the protein and RBC and
causes DISEASE
Changes in a single DNA base

Insertions and
deletions

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Can have disastrous
effects.
Change the reading
frame of the gene.
But mistakes happen –
DNA repair
Mutations are rare

The cell uses DNA
proofreading mechanisms to
correct these mistakes

The daughter strand is compared
to the parent DNA to check for
mistakes

Proofreading is not perfect –
mutations are still possible, although
rare
Mutations–key features

Mutations are rare changes in DNA

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can affect genes and the proteins they
encode
Mutations are inherited only if they
occur in germ-line cells
Mutations are important for genetic
variation and evolutionary change
How Genes Are Controlled
How do different kinds of cells
arise?


4 of the over 200
types of human
cells
They all contain
the same DNA,
so what makes
them different?
Gene activity is regulated

When cells differentiate

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Certain genes are turned
on and off.
Cells become specialized

Fertilized
egg
Blastula

Different types of cells express
different combinations of genes
Muscle cells make
contractile proteins (actin
and myosin)
Blood cells make
hemoglobin
How do cells switch genes on
and off?

Main switch point
occurs at
transcription
X
Genes
Glycolysis
enzymes
X
X
X
Hemoglobin
–
–
X
Myosin
X
–
–
Insulin
–
–
–
Example of transcriptional control:
Lactose intolerance
Turning on a gene

Proteins called transcription factors
interact with DNA → switch on
transcription


Lactose is a
disaccharide found
in milk.
Many adults have
trouble digesting
lactose

they lack the
digestive enzyme
that breaks down
lactose.
Genetic basis of lactose
intolerance


C→T mutation in the
promoter of the
lactase gene allows
some groups to
digest milk
Transcription of the
gene is not turned
off in adults
Other ways cells control gene
expression

RNA processing


Lactase
gene

C→T
The introns are removed
The remaining RNA is
spliced together
Different cells start with
the same RNA transcript
but cut out different
introns
different proteins
Turning on a gene


Cells secrete chemical
signals, or hormones,
that turn on
transcription
Important for
coordinating cell
activities.
The Genetic Basis of Cancer
Cancers are caused by
mutations in genes
Cancer = most frequent cause
of death in U.S.

Cancer Cells Have

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Abnormal shape
Not specialized
Immortal (able to divide
continually)
Normal cervical cells Cervical cancer cells
What Is Cancer?


Cells growing
out of control
They lose
control over cell
division
3D Medical Animation - What is Cancer? 1:06
http://www.youtube.com/watch?v=LEpTTolebqo&NR=1&feature=fvwp
What Is Cancer?


A disease of the cell cycle
Often results from mutations
in cyclins, proteins that help
regulate the cell cycle

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What causes Cancer?

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Mutations that damage
DNA
Environmental carcinogens

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Many “oncogenes” code for
cyclin proteins
Cancer cells do not respond
normally to the cell cycle
checkpoints

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Some viruses
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= Cell cycle checkpoints
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Tumor suppressor proteins

Tumor suppressor proteins keep division in
check by killing damaged cells

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Growth factors
Cyclins
Tumor-suppressor
genes
DNA repair proteins
HPV virus
Hepatitis B and C viruses
Epstein-Barr virus
Mutations in DNA repair genes
cause cancer

Mutations in different genes
cause cancer
Tobacco smoke
X-rays
UV radiation in sunlight and
tanning lamps
DNA repair or proofreading
genes make enzymes that
help the cell fix mutations in
its DNA.
When a DNA repair gene is
mutated, the cell can’t
repair mistakes in its DNA.
These mistakes build up
until an oncogene is hit.
Then the cell becomes
cancerous.
It takes several mutations to
create a cancer cell
Is Cancer Inherited?
Usually not
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Most mutations occur in the organ where the cancer
starts
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e.g. the colon or lung
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Usually germ-line cells aren’t affected
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But cancer-causing mutations sometimes do

the mutations are not passed from parent to child
occur in gametes
Case study: 52-year old
woman with colon cancer
Workup

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Anemic
Stool blood test was positive
BRCA1, an inherited cancer gene

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In the vast majority of cases,
breast cancer is not caused by
inherited mutations
The normal BRCA1 codes for
a tumor suppressor protein
Some mutations in the BRCA1
gene inactivate the tumor
suppressor protein → puts a
woman at high risk for breast
and ovarian cancers.
Mammograms of healthy (left)
and cancerous (right) breasts
Case study: 52-year old
woman with colon cancer
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Colonoscopy
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Treatment
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Mass was found in the descending colon
Biopsy tested positive for cancer
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Abdominal CT scan
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Lesion in the same area of her colon
Liver and chest CT scans were negative
Questions
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Surgery to remove
the tumor
Pathology report:
stage II lesion
Chemotherapy
What characteristics of cancer cells
distinguish them from normal cells?
Why do cancer cells form tumors?
Why did they do a CT scan of the liver
and chest?
Why would the doctor recommend both
surgery and chemotherapy?
Why cancer cells form tumors

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Normal cells stop
dividing when they
come in contact with a
neighbor
Cancer cells have lost
all restraint

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Pile on top of one
another
Grow in multiple layers