Download Lecture # 5 Mutations

Lecture #5 Mutations
Unit: Molecular Genetics
What is a mutation?
Now and then cells make mistakes in
copying their own DNA, inserting the
wrong base or even skipping a base as a
strand is put together.
Mutations are heritable changes in genetic
information.
What causes mutations?
Spontaneous Mutations. Some mutations
seem to be due a mistake in base pairing
during DNA replication.
Mutagens- chemical or physical agents in
the environment that cause mutations.
Examples of chemical mutagens: certain
pesticides, a few natural plant alkaloids,
tobacco smoke, and environmental
pollutants.
Examples of physical mutagens: some
forms of electromagnetic radiation, such as
X-rays and ultraviolet light.
If mutagens interact with DNA, they can
produce mutations at high rates.
Cells can sometimes repair the damage;
but when they cannot, the DNA base
sequence changes permanently.
If a gene in one cell is altered, the
alteration can be passed on to every cell
that develops from the original one.
If the mutation is in a gamete, the alteration
will be passed on to every cell in the
individual.
Effects of Mutations
The effects of mutations on genes vary
widely. Mutations may be….
1. Neutral (have little or no effect on the
organism)
2. Beneficial (proteins with new or altered functions
that can be useful to the organism in a different/
changing environment)
3. Harmful (these mutations may disrupt gene
function/ protein function)
Beneficial Effects
Some of the variation produced by
mutations can be highly advantageous to an
organism or species.
Mutations often produce proteins with new
or altered functions that can be useful to
organisms in different or changing
environments.
Without mutations, organisms cannot
evolve, because mutations are the source of
genetic variability in a species.
Example of a beneficial mutation - Polyploidy
Polyploidy
occurs when
all the
chromosomes
are present in
three or more
copies.
Polyploidy is common in plants and
rare in animals.
Most Crop Species are Polyploid
Polyploids (like the one on the left) are often larger and stronger
than their diploid ancestors (strawberry on right).
Harmful Effects
Some of the most harmful mutations are
those that dramatically change protein
structure or gene activity.
The defective proteins produced by harmful
mutations can disrupt normal biological
activities, and result in genetic disorders.
Take 2 minutes to summarize what
mutations are, what causes them, and
the effects mutations may have on an
organism.
Types of Mutations
All mutations fall into two basic groups
1. Gene Mutations - Mutations that
produce changes in a single gene
2. Chromosomal Mutations - Mutations
that produce changes in whole
chromosomes.
1. Gene Mutations
Point mutations - Mutations that involve
changes in one or a few nucleotides.
• They are called ‘point mutations’ because
they occur at a single point in the DNA
sequence.
• They generally occur during replication.
Sickle cell disease is
caused by a point
mutation
Symptoms of the
disease include
anemia, severe
pain, frequent
infections, & stunted
growth.
There are different types of Point
mutations
a. Substitutions
• In a substitution, one base is
changed to a different base.
• Substitutions usually affect no more
than a single amino acid, & sometimes
they have no effect at all.
b. Insertion – a
point mutation in
which one base is
inserted into the
DNA sequence.
c. Deletion- a point
mutation in which
one base is
removed from the
DNA sequence.
Insertion & Deletion point mutations are
also called as ‘Frameshift mutations’
Frameshift mutations - mutations that shift
the ‘reading frame’ of the genetic message.
Frameshift mutations can change every
amino acid that follows the point of the
mutation and can alter a protein so much
that it is unable to perform its normal
functions.
Analogy for the effect a frameshift mutation
can have on the reading frame.
Normal: the dog bit the cat
After an deletion mutation: the dob itt hec at
Mutations can also be classified according to
their effects on the protein (or mRNA)
produced by the gene that is mutated.
a. Missense- code for a different amino acid
b. Nonsense- code for a stop, which can
shorten the protein
c. Silent- code for the same amino acid
(AA).
d. Sense- mutation changes a stop codon to
an amino acid codon, which can lengthen
the protein.
Take 2 minutes to summarize what you
have learned about gene mutations,
focusing on the different types of point
mutations that can occur and the effect
those mutations may have on the protein
the gene codes for.
2. Chromosomal Mutations
These types of mutations change the
number or structure of chromosomes.
There are 4 types of chromosomal mutations
1. Deletion
This type of mutation
involves the loss of
all or part of a
chromosome.
A Boy with Cri-du-Chat Syndrome – a Debilitating
Disorder Caused by Chromosome Deletion
Cri-du-Chat is Caused by the Loss of the Short Arm of One Copy of
Chromosome 5
2. Duplication
This type of
mutation produces
an extra copy of all
or part of a
chromosome.
3. Inversion
This type of
mutation reverses
the direction of
parts of a
chromosome.
4. Translocation
This type of
mutation occurs
when part of one
chromosome
breaks off &
attaches to another.
Translocations Lead to a Number of Human Cancers
In Burkitt’s lymphoma, a
chromosome translocation
causes a cell cycle-promoting
gene to always be active.
Aneuploidy occurs when one of the
chromosomes is present in an
abnormal number of copies.
Trisomy and monosomy are two forms of
aneuploidy.
Down Syndrome is
Caused by Trisomy
for Chromosome 21
Aneuploidy is remarkably
common, causing
termination of at least
25% of human
conceptions.
It is also a driving force in
cancer progression
(virtually all cancer cells
are aneuploid).
What causes aneuploidy?
Chromosome Non-Disjunction in Meiosis
causes Aneuploidy
The Frequency of Chromosome Non-Disjunction And Down Syndrome Rises Sharply
with Maternal Age
The phenomenon is clear – the explanation isn’t.
Sex Chromosome Aneuploid Conditions are Common
Klinefelter syndrome
Take 2 minutes to summarize the different
types of chromosome mutations that may
occur in an individual.
Detection/ Diagnosis
There are genetic tests available for many of
the human genetic disorders. DNA, RNA,
chromosomes or proteins may be analyzed
in order to make the diagnosis.
Testing may be done for a variety of
reasons, such as in order to determine if an
individual carries a defective gene that runs
in their family.
Many genetic disorders can also be
diagnosed in early pregnancy.
Tests used to search for chromosomal defects in
early pregnancy - Amniocentesis and Chorionic
Villus Sampling
Pre-Implantation Genetic Diagnosis (PGD)
Removing a cell for
diagnosis from a human
embryo.
As a part of in vitro fertilization, this technique
may be used to search for chromosome and
gene defects prior to implanting the zygote
into the women’s uterus.
Take 2 minutes to summarize how
genetic disorders may be diagnosed.