6/2/2021

Mutations,
Variations and its
Consequences
Dr. Fariha Khan
BIO231
BSC208

Types of Genetic Variations

1. Point mutations and minor
insertions and deletions
2. Structural Variation: Copy
Number Variations (CNV)
• The term copy number
variation (CNV) is most often
applied to a change in copy
number of sequences that
result in larger deletions and
insertions, usually above 1 kb
nucleotides up to megabases in
size

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Mutation: Alterations in DNA Sequence

• A mutation is defined as an inherited change in genetic
information; the descendants may be cells or organisms.
• Mutation is the source of all genetic variation---the raw material of
evolution.
• The DNA in any cell can be altered through environmental exposure to
certain chemicals, ultraviolet radiation, other genetic insults, or even
errors that occur during the process of replication
• The ability of organisms to adapt to environmental change
depends critically on the presence of genetic variation in natural
populations
• A single base change can create a devastating genetic disorder or a
beneficial adaptation, or it might have no effect.

Categories of Mutations
• There are two broad categories of mutations:
• Somatic mutations
• Germ-line mutations
• Somatic mutations occur in non-reproductive cells (somatic cells); they
are passed to daughter cells during mitosis but not to offspring during
sexual reproduction.
• Germ line mutation occurs in a germ-line cell (one that will give rise to
gametes, i.e., egg or sperm cells), then this mutation can be passed to
an organism's offspring. This means that every cell in the developing
embryo will carry the mutation.

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Mutations can occur in germ-line cells or somatic cells.

Mutations and Polymorphisms

• While a mutation is defined as any alteration in the DNA sequence,
• Biologists use the term "single nucleotide polymorphism" (SNP) to
refer to a single base pair alteration that is common in the
population
• Specifically, a polymorphism is any genetic location at which at least
two different sequences are found, with each sequence present in
at least 1% of the population.
• The term "polymorphism" is generally used to refer to a normal
variation, or one that does not directly cause disease.

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Types of Gene Mutations

➢ The term gene mutation is used for a relatively small DNA lesion/changes
that affects a single gene
➢ A point mutation is a change in a single base pair within the DNA sequence
Class of Mutation Type of Mutation Description Human Disease(s) Linked
to This Mutation

Point One base is incorrectly added

during replication and replaces
Mutations Substitution the pair in the corresponding Sickle-cell anemia
position on
the complementary strand
One or more extra nucleotides
One form of beta-
Insertion are inserted into replicating DNA,
thalassemia
often resulting in a frameshift
One or more nucleotides is
"skipped" during replication or
Deletion Cystic fibrosis
otherwise excised, often resulting
in a frameshift

➢ A transition is the substitution of a purine for a purine or of a pyrimidine

for a pyrimidine;
➢ A transversion is the substitution of a pyrimidine for a purine or of a
purine for a pyrimidine

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Forward and Reverse Mutations

• At the most general level, we can distinguish a mutation on the basis
of its phenotype compared with the wild-type phenotype.

• A mutation that alters the wild-type phenotype is called a forward

mutation

• A reverse mutation (a reversion) changes a mutant phenotype back

into the wild type.

▪ The amino acids specified by

each mRNA codon.
▪ Multiple codons can code
for the same amino acid.
▪ The codons are written 5' to
3', as they appear in the
mRNA.
▪ AUG is an initiation codon;
UAA, UAG, and UGA are
termination (stop) codon

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Consequences of
Point mutations
within Genes
✓ The effects of
mutations on
protein structure.

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Phenotypic Effects of Mutations

➢Neutral Mutation : A missense mutation that alters the amino acid
sequence of the protein but does not change its function.
• Neutral mutations occur when one amino acid is replaced by another that
is chemically similar or when the affected amino acid has little influence on
protein function.
➢Loss of Function Mutations : Mutations cause the complete or partial
absence of normal protein function. A loss-of-function mutation so alters
the structure of the protein that the protein no longer works correctly or
the mutation can occur in regulatory regions that affect the protein
expression
➢Gain of Function Mutation: Mutation produces an entirely new trait or it
causes a trait to appear in an inappropriate tissue or at an inappropriate
time in development
• Others are lethal mutations, causing premature death

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Copy Number Variations (CNV)

• CNV is recognized as a form of structural
variation, involving changes of copy number
of a large segment of DNA (>1 Kb)
composed of duplications, deletions

• Complex multi-site variants introduced by

non-allelic homologous recombination

• CNV are estimated to cover ~12 – 15% of

the human genome

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Unequal crossing-over during

meiosis.
➢ When homologous chromosomes
misalign during meiosis, unequal
crossing-over occurs.

➢ The result is the deletion of a DNA

sequence in one chromosome, and the
insertion of a DNA sequence in the other
chromosome.

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