GENE MUTATIONS

Cytogenetics Finals
SKIN CANCERS
DNA MUTATIONS
WHAT ARE MUTATIONS? - Chemicals & UV radiation cause
mutations – skin cancer (if it is left
- Changes in the nucleotide sequence unthreatened or if mutations are
of DNA constantly developed).

In ultraviolet radiation, it has the capacity to

The primary structure of the DNA molecule: it
refers to the proper sequencing of the
nucleotides in the DNA and any changes to
that in the sequence of nucleotides is what we
call imitation.
form thymine dimers and these thymine
dimers cause an alteration of the primary
sequence of the nucleotides or it causes a
structural change in the primary sequence of
the DNA, which eventually can cause cancers.

SOMATIC CELLS

- May occur in somatic cells and are

not passed to offspring

Examples of somatic cells are the skin cells,

cells of the bones, and cells of the muscles.

- May occur in gametes (eggs and

sperms) and be passed to offspring.
- Mutations happen regularly (it is
very common).
- Almost all mutations are neutral
(does not harm organism). This illustration above shows examples of skin
cancers that are very common, especially in
Caucasians (these are white people or are the
descendants of white in origin). Skin cancers
are very common and most of it is due to - Some mutations may improve an
sunlight exposure. organism’s survival (beneficial)

Top picture at the right: basal cell carcinoma

which is the most common cancer worldwide.
Left picture: squamous cell carcinoma
Bottom right picture: Melanoma

REPAIR MECHANISM
- Many mutations are repaired by Some organisms have presented the picture
enzymes. above: they have mutations in terms of their
color, and this is a highly adaptable
mechanism for them to camouflage with their
surroundings to protect them from prey.

TYPES OF MUTATIONS

1. Chromosomal
2. Gene

CHROMOSOMAL MUTATIONS
- May involve:
• Changing the structure of a
chromosome.
• The loss or gain of part of a
For example, if a certain cell undergoes chromosome.
mutation, we have several repair mechanisms - Five types exist:
to which our cells would adapt or would try to • Deletion
prevent transmitting or passing it through the • Inversion
next cellular progenies • Duplication
• Translocation
- Some types of skin cancers and • Nondisjunction
leukemia result from somatic
mutations. DELETION
- Can you “catch” cancer from - Due to breakage (of the chromosomal
someone? (it is easily transmittable or structure).
contiguous?) NO! (But there are some - A piece of a chromosome is lost.
cancers that can be easily transmitted
sexually such as cervical cancer:
caused by human papillomavirus that is
usually obtained from sexual exposure.
There are also some cancers that are
associated with infectious agents such
as nasopharyngeal carcinoma and
some lymphomas that are associated
with Epstein-Barr virus infection. INVERSION
 - Chromosome segment breaks off.
- Segment flips around backward and
reattaches.

Duplication occurs when there is extra the

same segment is duplicated. We have another
copy that is inserted within that chromosome.
Deleted, we have a certain portion of the
You have a breaking chromosome and then
chromosome is removed. Inversion a
the segment flips backward and reattaches
segment that is broken off and then the
resulting to have a different sequence of the
segment flips around backwards and
DNA in the chromosome. Also, a type of
reattaches.
chromosomal mutation or chromosomal
aberration.
TRANSLOCATION
- Involves two chromosomes that are
DUPLICATION
not homologous (similar)
- Occurs when a gene sequence is
- Part of one chromosome is
repeated.
transferred to another
chromosomes.

So above, we have chromosome a and

chromosome b, and then there is the
breakage of these parts or the segments of
the chromosome and transferred to one
chromosome that is not homologous
SUMMARY OF CHROMOSOMAL (meaning they are not the same chromosome
ABERRATIONS number) then you resort to translocation.
The illustration above shows the balanced 3. Robertsonian
translocation, we also have one type of translocation – of
translocation, the Robertsonian chromosomes 14 and 21.
translocation in which the long arms of the - Turner syndrome
chromosomes are attached to one another. • Monosomy x – no extra x
For example, chromosome A and chromosome, you have only
chromosome B. The long arms of one x chromosome.
chromosome A and the long arms of - Klinefelter’s syndrome
chromosome B are attached to one another • You have an extra x
and then you have the fusion of the short arms chromosome (trisomy x)
from chromosome A to chromosome B. Then
the shorter chromosome and the longer
chromosome are formed.

NONDISJUNCTION
- Failure of chromosomes to separate
during meiosis (making of sperm or
egg). Meiosis is a prerequisite process
for spermiogenesis and oogenesis.
- Causes gamete to have too many or
too few chromosomes.

There is a failure of one chromosome for the

duplicated state of a chromosome to separate
from each other, which therefore causes the
other cell to have more chromosomes than
the other one.

DOWN SYNDROME
DISORDERS CAUSED BY
NONDISJUNCTION:
- Down syndrome
• 3 Major causes for Down
syndrome.
1. Non-disjunction – leading
to trisomy 21.
2. Mosaicism
Usual clinical features of Down Syndrome/
the typical fascist of Down Syndrome
GENE MUTATIONS DELETION
- Change in the nucleotide sequence
of a gene.
- May only involve a single nucleotide.
- May be due to copying errors,
chemicals, viruses, etc.

TYPES OF GENE MUTATIONS

Include:
- Point Mutations
• Substitutions
• Insertions
• Deletions
- Frameshift Mutations

POINT MUTATION
- Change of a single nucleotide.
- Includes the deletion, insertion, or
substitution of ONE nucleotide in a
gene.
- Sickle Cell disease is the result of
Deletion – portion of the DNA is deleted, there
one nucleotide substitution. Occurs
will be removal of the genes.
in the hemoglobin gene.
• Hemoglobin is a protein. It is a
quaternary type of protein; it
consists of more than one
subunit. We have four subunits
in hemoglobin: alpha, and beta.
We have 2 alpha globin and 2
beta globin.
• In sickle cell disease you have a
midpoint mutation in the beta-
globin genes, so this would
result in a change in the
structure of hemoglobin which
eventually results in the change
of the shape of the red blood
cell, which is normally
biconcave round to form a sickle
shape or a crescent shape cell.
The possible complication of sickle cell
disease is thrombosis. The sickle cell would
block blood flow and would result in poor
blood supply to the tissue that it supplies. So,
it will result into ischemia and then
thrombosis.
SUBSTITUTION
- A single nucleotide is substituted
with (or exchanged for) a different
nucleotide that may result in an
altered sequence of amino acid.
INSERTION
- Nucleotides are inserted into
sequence altering codon pattern.
The illustration below shows the importance of
point mutation in relation to the primary
structure of amino acids. This amino acid
sequence is amino acid sequence of
hemoglobin that would if there will be
mutations, it can result to sickle cell anemia.
Normally in the normal hemoglobin we have
glutamic acid. Now what happens in sickle cell
disease is that you have a point mutation in
one nucleotide coding from glutamic acid
from GAG to GTG which then results in valine.
Valine has a very different biochemical
property from that of glutamic acid in which
valine is a hydrophobic amino acid while
glutamic acid is a hydrophilic glutamic acidic
amino acid. Therefore, it will generally result
to changes in the secondary as well as the
tertiary structure of amino acid.
FRAMESHIFT MUTATION
- Inserting or deleting one or more
nucleotides.
- Changes the “reading frame” like
changing a sentence.
- Proteins built incorrectly.
- Original:
• The fat cat ate the wee rat.
- Frame Shift (“a” added):
• The fat caa tet hew eer at.
In a frameshift mutation, in deletions, if you
delete a certain nucleotide, it will also result in
different codons that would code for a
different amino acid. Above you can see the
original nucleotide sequence and if you
remove this guanosine residue, it now results
in the disarrangement of nucleotides and
there will be different information or amino
acid that will be coded. Therefore, a different
primary structure of proteins and a different
protein.

MUTATIONS AND DISEASES

Cystic A recessive disorder caused

Fibrosis by mutations in the CFTR
gene. The major symptom is
the thick mucous in the lungs,
leading to infections. Aside
from that, patients with cystic
fibrosis would have
gastrointestinal symptoms such
as meconium ileus. Most of
these individuals will have a
salty sweat. One of the
definitive diagnoses of cystic
fibrosis is determining the
chloride level in the sweat.

Sickle Cell A recessive disorder caused

Anemia by mutations in the beta
globin gene. Red blood cells
take on sickle shape,
interfering with normal
circulation, and depriving
organs of oxygen.
Huntington A dominant condition caused
Disease by mutations in the
Huntington gene. Symptoms
begin in adulthood and
include uncontrolled
movements and cognitive
impairment.