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 is common in plants and rare in animals.

Polyploidy occurs when all the chromosomes are present in three or more copies.  

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 mutationcan 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.