DATE:

COURSE SUBJECT: GENETICS

STUDENT: BENJAMIN ABELLA INSTRUCTOR: SHARINA FIDEL

TOPIC: VARIATIONS AND MUTATIONS

amphibians. Polyploidy originates in

I. CHROMOSOMAL MUTATIONS two ways:
Your body's 46 chromosomes, which are o Autopolyploidy- addition of
composed of 23 matched pairs of DNA and one or more extra sets of
protein rods, are found in the majority of your chromosome, identical to the
cells. Tens of thousands of genes are contained normal haploid complement of
on these chromosomes, which direct your body's the same species.
growth and maintenance throughout your o Allopolyploidy – The
lifetime. combination of chromosome
sets from different species
The delicate balance of the human body may be ocuuring as a consequence of
thrown off if a chromosome pair gains or loses a hybridization
member, or even just a portion of a member. Each set of chromosomes is designated
by n. Below are some other types of
VARIATIONS IN CHROMOSOME NUMBER ploidy:
• Aneuploidy - the unusual case where
one or more chromosomes from a - Haploid (n) – with one set of
normal set are absent or present in chromosomes
more copies than usual. - Diploid (2n) – with two sets of
o Nullisomy - the loss of both chromosomes
pairs of homologous - Triploid (3n) – with three sets of
chromosomes; individuals are chromosomes
called nullisomics and their - Tetraploid (4n) – with four sets of
chromosomal composition is chromosomes
2N-2
o Monosomy - the loss of a
single chromosome;
individuals are called
monosomics and their
chromosomal composition is
2N-1
o Trisomy - the gain of an extra
copy of a chromosome;
individuals are called trisomics
and their chromosomal
composition is 2N+1 VARIATIONS IN CHROMOSOME
o Tetrasomic - the gain of an STRUCTURE AND ARRANGEMENT
extra pair of homologous
chromosomes; individuals are
Chromosomal Rearrangements
called tetrasomics and their
Large sections of chromosomes (rather than
chromosomal composition is
entire chromosomes) are affected by a different
2N+2
class of large-scale mutations. These alterations
• Euploidy - chromosomal variation
are known as chromosomal rearrangements.
occurs when a cell or organism's
This includes:
normally complete set of chromosomes
is altered, producing multiples of the
haploid or basic number of
chromosomes.
• Polyploidy - heritable condition of
possessing more than two complete
sets of chromosomes. Polyploids are
common among plants, as well as
among certain groups of fish and
 results in every cell in the body
- A duplication, where part of a chromosome having only one X
is copied. chromosome. It causes many
- A deletion, where part of a chromosome is traits and problems. Girls with
removed.
- An inversion, where chromosomal region is
flipped around so that it points in the
opposite direction.

TS are shorter than most girls.

They don't go through normal
- A translocation, where a piece of one
puberty as they grow into
chromosome gets attached to another
adulthood. They may also
chromosome. A reciprocal translocation
have other health problems
involves two chromosomes swapping
such as heart or kidney
segments; a non-reciprocal translocation
problems.
means that a chunk of one chromosome
moves to another.
o Trisomy 21 (Down’s
Syndrome)- the person has
three copies of chromosome
GENETIC CONSEQUENCES AND
21, instead of the usual two
PHENOTYPIC EFFECTS
copies, in all cells. This extra
copy changes how the baby's
NUMERICAL ABNORMALITIES
body and brain develop, which
- When an individual is missing one of the can cause both mental and
chromosomes from a pair, the condition is physical challenges for the
called monosomy. When an individual has baby.
more than two chromosomes instead of a
pair, the condition is called trisomy.

• Non-Disjunction- The failure of

homologous chromosomes to separate
properly during meiosis. Non-
disjunction of chromosomes result to
unequal distribution of chromosomes in
the gametes causing chromosomal
abnormalities.
o Trisomy 18 (Edward’s
Syndrome)- Edwards
syndrome, also known as
trisomy 18, is a very severe
genetic condition that affects
how your child’s body
develops and grows. Children
diagnosed with trisomy 18
have a low birth weight,
multiple birth defects and

o Monosomy X (Turner’s
Syndrome)- The complete
absence of an X chromosome
generally occurs because of an
error in the father's sperm or
in the mother's egg. This
 defining physical STRUCTURAL ABNORMALITIES
characteristics. - A chromosome’s structure is altered due to
o Trisomy 13 (Patau either deletion, duplication, or translocation
Syndrome) - Individuals with
trisomy 13 often have heart o Cri-du-chat- Cri-du- chat is
caused by a deletion of
chromosome 5p, which is written
"5p-." Babies with Cri-du-chat have
a high-pitched cry, poor muscle
tone, a small head size, and low
birth weight.

o Pallister-Killian Syndrome-
Pallister-Killian syndrome is a result
defects, brain or spinal cord
of extra #12 chromosome
abnormalities, very small or
material. Babies with this
poorly developed eyes
syndrome have many problems.
(microphthalmia), extra
These include severe intellectual
fingers or toes, an opening in
disability, poor muscle tone,
the lip (cleft lip).
"coarse" facial features, and a
o Trisomy 16 - most common
autosomal trisomy in humans
which is almost uniformly
embryonic lethal.
prominent forehead.

II. GENE MUTATIONS

A genetic mutation is a change in a gene's DNA
sequence that results in the production of a
different organism. It alters the DNA sequence
of that gene in a way that is permanent.

MUTATIONS BASED ON LOCATION

Mutations can be classified based on their origin. It
o Klinefelter Syndrome can either be spontaneous or induced.
(Double X-Syndrome) - a • Spontaneous- Occurs in absence of
genetic condition that results known mutagen. These mutations are
when a boy is born with an statistically random unpredictable
extra copy of the X events.
chromosome. Klinefelter • Induced- Occurs in the presence of
syndrome is a genetic known mutagen or outside factor such
condition affecting males, and as radiation and other chemicals.
it often isn't diagnosed until
adulthood. MUTATIONS BASED ON TYPE OF MOLECULAR
CHANGE
Mutations based on molecular changes can be
classified into three: Base substitutions, deletions,
and insertions.
• Base Substitutions- Single base
substitutions are called point mutations,
recall the point mutation Glu -----> Val
which causes sickle-cell disease. Point
mutations are the most common type of
mutation and there are two types.
o Transition: this occurs when a
purine is substituted with another
 purine or when a pyrimidine is
substituted with another
pyrimidine.
o Transversion: when a purine is
substituted for a pyrimidine or a
pyrimidine replaces a purine.

Point mutations that occur in DNA

sequences encoding proteins are either
silent, missense or nonsense.
• Deletions- A deletion, resulting in a
o Silent: If abase substitution
frameshift, results when one or more base
occurs in the third position of the
pairs are lost from the DNA (see Figure
codon there is a good chance that
above). If one or two bases are deleted the
a synonymous codon will be
translational frame is altered resulting in a
generated. Thus, the amino acid
garbled message and nonfunctional
sequence encoded by the gene is
product. A deletion of three or more bases
not changed and the mutation is
leave the reading frame intact. A deletion of
said to be silent.
one or more codons results in a protein
o Missence: When base
missing one or more amino acids. This may
substitution results in the
be deleterious or not.
generation of a codon that
• Insertions- The insertion of additional
specifies a different amino acid and
base pairs may lead to frameshifts
hence leads to a different
depending on whether or not multiples of
polypeptide sequence. Depending
three base pairs are inserted. Combinations
on the type of amino acid
of insertions and deletions leading to a
substitution the missense mutation
variety of outcomes are also possible.
is either conservative or
nonconservative. For example, if
the structure and properties of the SPONTANEOUS VS. INDUCED MUTATIONS
substituted amino acid are very
similar to the original amino acid SPONTANEOUS MUTATIONS
the mutation is said to be These are naturally occurring mutations that result to
conservative and will most likely natural changes in the stricture of the DNA. All types
have little effect on the resultant of point mutations can occur spontaneously during S,
protein structure / function. If the G1, and G2 phases of the cell cycle or by the
substitution leads to an amino acid movements of transposons.
with very different structure and
properties the mutation is Causes of Spontaneous Mutations
nonconservative and will probably • Tautomeric Shift- Occurs when purine
be deleterious (bad) for the and pyrimidine bases exist in different
resultant proteins structure / chemical forms known as tautomer. This
function (i.e. the sickle cell point also happens when the position of protons
mutation). in the DNA bases changes.
o Nonsense: When a base
substitution results in a stop codon
ultimately truncating translation
and most likely leading to a
nonfunctional protein
 • Chemical Changes- Occurs when there is
a spontaneous chemical change in the
structure of the nucleotide bases.
o Depurination- the loss of a
purine base from a nucleotide

• Wobble Base Pairing- Normal, o Deamination- the loss of an

protonated, and other forms of the bases amino group (NH2) from a base.
are able to pair because of flexibility in the
DNA helical structure.

INDUCED MUTATIONS
These are the mutations that result from changes caused
by environmental chemicals or radiation.
• Strand Slippage- This may occur when
Mutagen- Any environmental agent that significantly
one nucleotide strand forms a small loop. If
increases the rate of mutation above the spontaneous
the looped out nucleotides are on the newly
rate.
synthesized strand, an insertion results.
Charlotte Auerbach- The first to discover a chemical
mutagen.

Causes of Induced Mutations

• Base Analogs- These are chemicals with similar
strictures to that of any of the four standard
bases of the DNA. DNA polymerases cannot
distinguish these analogs from the standard
bases so, if base analogs are present during
replication, they may be incorporated into the
newly synthesized DNA molecules. Example here
is the 5-Bromouracil.

• Unequal Crossing Over- May result from

misalignment of pairs which results in one
DNA molecule with an insertion and the
other with a deletion.

• Alkylating Agents- these are chemicals that

donate alkyl groups including methyl CH3) and
ethyl (CH3—CH2), which are added to nucleotide
bases by some chemicals. An example is the
addition of an ethyl group to a guanine base by
the ethylmethanesulfonate (EMS) producing 6-
ethylguanine, which pairs with thymine.
• Deamination- In addition to its spontaneous
occurrence, deamination can be induced by
some chemicals. Example, nitrous acid
deaminates cytosine, creating uracil which in the
next round of replication pairs wit adenine
producing a CG:TA transition mutation.
DNA REPAIR SYSTEMS
A strict definition of DNA repair is the cellular responses
involved in restoring the normal base-pair sequence and
structure of damaged DNA.

• Direct Reversal Repair- Some DNA and RNA

modifications are removed using direct reversal
repair rather than excision, resynthesis, or
ligation. Therefore, direct reversal repair is error-
• Hydroxylamine- it is a very specific base free and maintains genetic information because
modifying agent that adds a hydroxyl group to it does not call for breaking of the
cytosine converting it into phosphodiester backbone.
hydroxyaminocytosine. The tautomer pairs with
adenine instead of guanine and leads to CG:TA
transitions.

• Oxidative Reactions- reactive forms of oxygen

• Excision Repair- Nucleotide excision repair
damage DNA and induce mutations by bringing
removes DNA damage by first cutting the
chemical changes to DNA. Examples of this
damaged strand on both sides of the lesion, then
include Superoxide radicals, Hydrogen peroxide,
filling the gap with repair synthesis using the
and hydroxyl radicals.
intact strand as a template, and finally ligating
the repaired DNA.
o Base Excision Repair- The main DNA
repair pathway, known as base excision
repair (BER), is responsible for repairing
base lesions brought on by oxidative,
alkylation, deamination, and
depurination/depyrimidination damage.
• Intercalating Agents- They produce
mutations by sandwiching themselves between
adjacent DNA bases. They distort the three-
dimensional structure of the helix causing single-
nucleotide insertions ad deletions in replication.
Examples are prolavin, acridine orange, ethidium
bromide, and dioxin.

• Radiation- ionizing radiation breaks covalent

bonds including those in DNA and is the leading
cause of chromosome mutations. UV (254-260
nm) causes purine and pyrimidines to form
abnormal dimer bonds.
o Nucleotide Excision Repair- A
mechanism known as nucleotide
excision repair involves removing a
damaged section of DNA and replacing
it with new DNA that is synthesized
 using the undamaged strand as a
template.

• Mismatch Repair- a procedure that fixes

mismatched nucleotides in otherwise
complementary paired DNA strands that result
from base modifications, recombination errors,
and DNA replication errors.