Mutations
Reading
• Handout
• Recommended web sites
Learning objectives
• Understand the causes and effects of DNA
mutations
• Be able to distinguish between germline
and somatic mutations
• Know the most common small and large
scale mutations
Mutation:
A
T
C
Change in
number
Change in
arrangement
A
A
C
Change in
sequence
A change in the genetic material (DNA)
A change in the number, arrangement or sequence of
nucleotides in a gene
 Changes can be on a small or big scale
Classification of mutations
Classification according to:
1) Type of the cell: somatic or germline mutation
2) level of change: chromosomal or DNA sequence
big
3) Effect on the protein (phenotype):
misense / non sense / silent / frame shift
4) The cause of mutation: spontaneous or Induced
Hereditary (germline) vs acquired (somatic)
Hereditary (germline):
 occurs in sperm,
ovum or zygot.
 mutation affects all
body cells
 can be transmitted
to offspring.
Hereditary (germline) V.s acquired (somatic)
Acquired (somatic):
 occurs in somatic cells
Normal somatic cells
mutation
 mutation affect group of
cells
cannot be transmitted to
offspring.
Abnormal cell
population
e.g cancer cells
Normal cell
population
Chromosomal mutations
A) Change in number:
Aneuploidy: loss or gain of
whole chromosomes
Chromosomal mutation
B) Change in arrangement:
Change in DNA sequence
Classified according to:
A) Chemical nature of base changed:
purines
A
pyrimidine
Transversion
C
Transition
Transition
G
T
Transversion
B) Effect in the protein: mutation in exons
Substitution (point mutation): silent / missense /
nonsense Frame-shift: deletion / insertion
a) Silent mutation:
Change in DNA sequence does not cause change in amino
acids
U to C
AUGGCU
AUGGCC
Met- Ala
Met- Ala
b) Misense mutation: changes the amino acid
AUGGCU
Met- Ala
A to U
UUGGCC
Leu- Ala
c) Nonsense mutation:
• Change in DNA sequence leads to formation of stop codon.
• Leads to the formation of incomplete protein
Template
Mutation: G  A
Template
Frame-shift mutation:
Insertion or deletion of 1-2 nucleotides causes change in the
entire protein sequence.
Template
Insertion of G
Template
Mutations :
Induced
Spontaneous
Mutations: Spontaneous
• Spontaneous mutation
Changes that occur during normal
genetic and metabolic functions in the
cell
1.Mistakes during DNA replication
2.Base modifications caused by
hydrolytic reactions
Mutations: Induced
• Induced mutation
Changes that occur as a result of
exposure to environmental agents
(mutagens)
1.Ionizing radiation
2.Chemicals
3.Ultraviolet light (UV-light)
The importance of DNA repair
Xeroderma pigmentosa
• Genetic disease caused by a lack of enzymes for
nucleotide repair
• Patients are extremely sensitive to sunlight
• The disorder leads to different forms of cancer
Genetic disorders
Learning objectives
• Understand the difference between dominant
and recessive mutations
• Know the main groups of genetic disorders
with examples from each group
• Be able to understand the pattern of
inheritance for single gene disorders
What is a genetic disorder?
• An illness caused by abnormalities in
genes or chromosomes
• The disorders can be grouped into 4:
1. Single gene
2. Chromosomal
3. Mitochondrial
4. Multifactorial
1. Single gene disorders
• Is caused by a mutation in a single gene
• Recessive inheritance: Two copies of
the gene must be mutated in order for
the disease to occur
• Dominant inheritance: Mutation in one
copy of the gene is sufficient to cause
the disease
Dominant and recessive mutations
1. Single gene disorders:
Autosomal dominant
Examples:
• Huntington’s
disease
• Neurofibromatosis
• Achondroplasia
• Polycystic kidney
disease
1. Single gene disorders:
Autosomal recessive
Examples
• Cystic fibrosis
• Albinism
• Phenylketonuria
(PKU)
• Sickle cell disease
• Tay-Sachs disease
1. Single gene disorders:
X-linked dominant
1. Single gene disorders:
X-linked dominant cont.
Examples:
• Rett syndrome
• Incontinentia
Pigmenti type 2
• Aicardi Syndrome
1. Single gene disorders:
X-linked recessive
1. Single gene disorders:
X-linked recessive cont.
1. Single gene disorders:
X-linked recessive cont.
Examples:
• Hemophilia A
• Duchenne muscular dystrophy
• Lesch-Nyhan syndrome
• Male pattern baldness
• Color blindness
1. Single gene disorders:
Y-linked
• Are caused by mutations on the Y
chromosome
• Every son of an affected father will be
affected
• Female offspring of affected fathers are
never affected
Example:
• Male infertility
2. Chromosomal disorders
Is caused by:
• Chromosomal mutations
• Numerical abnormalities:
 gain of a chromosome (trisomy)
 loss of a chromosome (monosomy)
Chromosomal deletion
syndromes
• Cri du chat
syndrome (5p
deletion)
• Wolf-Hirschorn
syndrome (4p
deletion)
Chromosomal insertion:
Fragile X syndrome
• Multiple insertions of three nucleotides (CGG)
creates a fragile X chromosome
Trisomy 21; Down syndrome
• Is caused by an extra copy of chromosome 21
XXY trisomy;
Klinefelter syndrome
• Is caused by the presence of an extra copy of
the X chromosome
X Monosomy;
Turner syndrome
• Is caused by the presence of only one copy
of the X chromosome
3. Mitochondrial disorders
• Is caused by mutation in mitochondrial
DNA
Examples:
• Kearns-Sayre syndrome
• Myoclonus epilepsy
• Mitochondrial encephalomyopathy
3. Mitochondrial disorders cont.
4. Multifactorial disorders
• Mutations in several genes in combination
with lifestyle and environmental factors
Examples:
• Heart disease
• Diabetes
• Asthma
• Cancer
Recommended links
• http://www2.estrellamountain.edu/facult
y/farabee/biobk/BioBookhumgen.html
• http://learn.genetics.utah.edu/content/di
sorders/whataregd/
Tutorial Questions
• A questions sheet about Mutations and
Genetic disorders is available on
Moodle