A mutation is a change in genetic material.
A mutation is a change in the DNA sequence or
Most mutation are the result of error during DNA
replication process/ error during DNA repair. Some types
of mutations are known to be caused by certain chemicals
and ionizing radiation, UV.
A mutation that arises
naturally and not as a result
of exposure to mutagens.
caused by mutagens;
Radiation, Chemicals, or
Spontaneous mutations on the molecular level can be caused by :
Tautomerism: A base is changed by the repositioning of a hydrogen atom,
altering the hydrogen bonding pattern of that base, resulting in incorrect base
pairing during replication.
Depurination: Loss of a purine base (A or G) to form an apurinic site (AP
Deamination: Hydrolysis changes a normal base to an atypical base
containing a keto group in place of the original amine group. Examples include
C → U and A → HX (hypoxanthine), which can be corrected by DNA repair
mechanisms; and 5MeC (5-methylcytosine) → T, which is less likely to be
detected as a mutation because thymine is a normal DNA base.
Slipped strand mispairing: renaturation in a different spot ("slipping") after
denaturation of the new strand from the template during replication. This can
lead to insertions or deletions.
A Mutagen is an agent of substance that can bring about a permanent alteration to
the physical composition of a DNA gene
Small scale mutation
Large scale mutation
Deletions of large chromosomal regions, leading to loss of the genes within those
Mutations whose effect is to juxtapose previously separate pieces of DNA, potentially
bringing together separate genes to form functionally distinct fusion genes (e.g., bcr-
abl). These include:
Chromosomal inversions: reversing the orientation of a chromosomal segment.
Loss of heterozygosity: loss of one allele, either by a deletion or a recombination event,
in an organism that previously had two different alleles.
A heritable change in the DNA.
Occurred in a germ cell and incorporated in every cell of the body.
Can be transmitted to the next generation.
Germline mutations play a key role in inherited genetic diseases.
Alterations in DNA that occur after conception.
Occur in any of the cells of the body except germ cell.
Can not transmitted to the next generation.
These alterations can (but do not always) cause cancer or other
Change the gene product such that it gains a new and abnormal function.
These mutations usually have dominant phenotypes.
Often called a neomorphic mutation.
The gene product having less or no function.
These mutations usually have recessive phenotypes. Exceptions are when the
organism is haploid, or when the reduced dosage of a normal gene product is not enough
for a normal phenotype (haploinsufficiency).
When the allele has a complete loss of function (null allele) it is often called
an amorphic mutation.
Lethal mutations are mutations that lead to the death of the organisms that carry the
A back mutation or reversion is a point mutation that restores the original sequence and
hence the original phenotype
Base substitutions are those mutations in which one base
pair is replaced by another.
Transition: The replacement of a base by the other base
of the same chemical category (purine/ purine;
Transversion: The replacement of a base of one chemical
category by a base of the other (pyrimidine/ purine;
Effect of Point Mutation
Silent mutation: Single substitution mutation when the change in the
DNA base sequence results in a new codon still coding for the same
Missense mutation: One triplet codon altered, results in one wrong codon
and one wrong amino acid.
Acceptable missense: This occur when single base change results in
replacement of one A.A by another with rather same function.
Non acceptable missense: This occur when single base change result in
the replacement of one amino acid with another with completely
Nonsense mutation: Change a codon that specifies an amino acid into a
termination codon lead to shortened protein because translation of the
mRNA terminate prematurely.
Introduction to Genetic analysis, Ninth edition, W.H. Freeman and Company
Sickle Cell Disease
It results from a single base change
in the gene for B-globin. The
altered base cause insertion of the
wrong amino acid into one position
of B globin protein.
These altered protein results in
distortion of red blood cells under
low oxygen conditions
Insertion/deletion can disrupt the grouping of the codons, resulting in a completely
Deletions: Remove information from the gene. A deletion could be as small as a
single base or as large as the gene itself.
Insertions: Occur when extra DNA is added into an existing gene.
Multiple of 3 (codon) / Not multiple of 3
Multiple of 3 (codon) causes loss or gain of codons and subsequently amino acids
in translated product.
Not multiple of 3
Altered reading frame or fram-shift, altered amino acid sequence, often premature
termination of protein through generation of termination codon with loss of
RNA Processing Mutation
RNA processing mutation
destroy consensus splice
sites, cap sites,
..Abnormal splicing often
leads to frameshift
mutations and premature
Result from: Misrepair of chromosome breaks or
Malfunction of the recombination system.
Balanced: no net gain or loss of chromosomal material,
Example: Translocation, inversion, ring chromosome.
UnBalanced: net gain or loss of chromosomal material
Example: Loss or duplication of whole chromosome arms.
Variation in Chromosome Number
Variations in the chromosome number (heteroploidy) can be mainly of
Euploidy: Change in whole chromosome sets.
Aneuploidy: Changes in part of chromosome sets. An additional or
Hypoploidy: Monosomy, nullisomy
Hyperploidy: Trisomy, Tetrasomy
Effect of Mutation
No effect (silent mutation)
Harmful effect that leads to outright disease or death.
Mutation that occur in utero are incompatible with life.
On rare occasions, A mutation result in a new characteristic which can help the organism
survive in unfavorable environmental condition. The new characteristic will be passed to
its offspring who can survive and others may die.
Human chromosomes segmented by rates of four types of mutations; human DNA is compared with DNA from other primates (e.g., orangutans –
in background) and then processed using a statistical segmentation technique. Credit: K. Makova and F. Chiaromonte
The various forms of spontaneous and induced DNA damage
give rise to a different types of molecular mutation:
MUTATION OR POLYMORPHISM
The quality of existing in several different forms.
SNP represents a variation of one base in the
The most common type of genetic variation.
Each individual has many single nucleotide
polymorphisms that together create a unique DNA
arrangement for that individual.
Single Nucleotide Polymorphism
SNP is a source variance in a genome. SNPs are the most simple form
and most common source of genetic polymorphism in human genome.
SNPs begin their existence as point mutations (nonsense mutation).
Two types of nucleotide base substitutions resulting in SNPs:
Transition: Substitution occurs between purines or pyrimidines.
Account 2/3 of all SNPs.
Transversion: Substitution occurs between purines and a pyrimidines.
Single Nucleotide Polymorphism
Distribution of SNPs
Coding region SNPs
The substitution causes no
amino acid change to the
protein it produces (silent
The substitution results in an
alteration of the encoded amino
acid. A non sense mutation
results in a misplaced
Synonymous Non Synonymous
Change in DNA sequence within cell. Some
mutation cause disease, others cause genetic
Change in DNA sequence lead to genetic
variation within individuals, groups or
No single allele is regarded as the standard
sequence. Instead there are two or more
equally acceptable alternatives.
Less common differences occurring in less
than 1% of the population.
Occurring in at least 1% of the population,
Mostly have been associated with disease (or
risk of disease) and May resulted from
damage by external agents (such as viruses or
Polymorphic DNA sequences can be used as
markers for determining allelic inheritance of
disease causing genes and for identity testing
Common mutation can be classified as
polymorphism. However, many mutation are
not polymorphic, they represented a rare
A rare disease allele in one population can
become a polymorphism in another if it
confers an advantage and increases in
MUTATION OR POLYMORPHISM
References and Online Further Reading
Ali Khalifa. Applied molecular biology; eds: ( Fathi Tash and Sanna Eissa). 109 pages. Egypt. University Book Center. 2002.
Daniel H. Farkas. DNA Simplified: The Hitchhiker's Guide to DNA. 110 pages. Washington, DC: AACC Press, 1996, ISBN 0-
915274-84-1. Available in paper copy from the publisher
Daniel P. Stites, Abba T. Terr. Basic Human Immunology: 336 Pages. Appleton & Lange (November 1990). ISBN. 0838505430.
Innis, David H. Gelfand, John J. Sninsky. PCR Applications: Protocols for Functional Genomics: 566 pages. Academic Press; 1
edition (May 17, 1999). ISBN:0123721865.
Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, and Peter Walter. Molecular Biology of the cell. 1392
pages. Garland Science; 5 edition (November 16, 2007).ISBN. 9780815341055.
Robert F. Mueller, Ian D. Young. Emery's Elements of Medical Genetics: Publisher: Churchill Livingstone. 1995 ISBN.
Robert F. Weaver. Molecular Biology. 600 Pages. Fourth Edition. McGraw-Hill International Edition. ISBN 978-0-
William B. Coleman, Gregory J. Tsongalis . Molecular Diagnostics. For the Clinical Laboratorian: 592 pages. Humana Press; 4th
Printing. edition (August 15, 2005). ISBN 1588293564
Eukaryotic promoter . Internet. Available from: http://www.patentlens.net/daisy/promoters/242/g1/250/1346.html
Transcription factor. Available from. Fred Hutchinson Cancer Research Center
Transcription factor . Internet. Table. Available from; http://oregonstate.edu/instruction/bb492/lectures/EuTranscriptionI.htm
All images belong to their respective authors
Salwa Hassan Teama 2014