MODULE

7 GENE AND CHROMOSOMAL MUTATIONS

Mutation 2. CELL TYPE
· Any heritable alteration in a gene or chromosome A. Somatic Mutation
· Permanent alteration of the nucleotide sequence of - Occurs in non-reproductive cells.
the genome of an organism, virus, or other genetic - Most common cancers result from somatic-cell
elements. mutations.
· Could be beneficial, neutral, or detrimental to the - Not passed along to the next generation by sexual
organism. means.
B. Germ-line Mutation
Gene Mutations - Occurs in reproductive cells.
Major Types of Gene Mutations Classified According To: - Mutation can be passed on to the next generation.
1. Origin
A. Spontaneous
B. Induced The Royal Disease.
2. Cell Type The X-linked blood disorder
A. Somatic hemophilia in European royal
B. Germ-line families is thought to have arisen
3. Expression in the germ cell line of Queen
A. Conditional Victoria or one of her parents.
B. Unconditional
4. Effect on Function
A. Loss-of-function
B. Hypomorphic 3. EXPRESSION
C. Hypermorphic A. Conditional Mutation
D. Gain-of-function - Expressed only under restrictive conditions (e.g.
5. Molecular Change high temperatures).
A. Base substitution - Ex. temperature-sensitive mutations.
B. Transition B. Unconditional Mutation
C. Transversion - Expressed under permissive as well as restrictive
D. Insertion conditions
E. Deletion · Permissive condition
6. Effect on Translation o Condition in which the phenotype of a
A. Synonymous conditional mutation is not expressed.
B. Missense · Restrictive condition
C. Nonsense o Condition in which a phenotype of a
D. Frameshift conditional mutation is expressed.

1. ORIGIN An enzyme involved in the

A. Spontaneous Mutation deposition of melanin in
- Occurs in the absence of known mutagen Siamese Cats is blocked at
B. Induced Mutation normal body temperature but
- Occurs in the presence of a known mutagen. expressed at colder
· Mutagen temperatures. The extremities
- An agent that is capable of increasing the rate of of the cat (tips of the legs,
mutation. ears, snout, and tail) have a
- Ex. Bromine, Benzene, X-rays, UV radiation, etc. characteristic pigmentation because these areas are cooler
than the rest of the body.
Potassium bromate, a
common baking ingredient 4. EFFECT ON FUNCTION
can cause oxidative A. Loss-of-function Mutation
damage to the DNA. - AKA Knockout or Null Mutation.
- Mutation that results in complete gene inactivation
or in a completely non-functional gene product.

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7 GENE AND CHROMOSOMAL MUTATIONS
- Ex. Deletion of all parts of a gene, amino acid · Purine  Pyrimidine
replacement that inactivates CHON. AT AC GT GC
B. Hypomorphic Mutation D. Insertion
- AKA Leaky Mutation - One or more nucleotides are added.
- Mutation that reduces, but does not completely
eliminate gene expression or the activity of the
gene product.
- Ex. Nucleotide substitution that reduces level of
transcription, amino acid replacement that impairs
protein function. E. Deletion
C. Hypermorphic Mutation - One or more nucleotides are missing.
- Produces a greater than normal level of gene
expression.
- Typically affects gene regulation.
D. Gain-of-function Mutation
- Qualitatively alters the gene action
- May cause a gene to become active in type of cell 6. EFFECT ON TRANSLATION
or tissue in which the gene is not normally active. A. Synonymous Substitution
- May result in the expression of a gene at a time in - AKA Silent substitution.
which the gene is not normally expressed. - Mutations in the nucleotide sequence do not
change the amino acid sequence.
5. MOLECULAR CHANGE - Particularly in mutations that occur in the third
A. Base Substitution codon position.
- One base pair in the DNA is replaced with a B. Missense Mutation
different base pair. - AKA Nonsynonymous mutation.
- Ex. A is replaced by G resulting to a temporarily - Mutations in the nucleotide sequence alter the
mismatched G-T base pair. amino acid sequence.
- Ex. Replacement in the AA sequence of
phenylalanine hydroxylase resulting to
- But at the very next replication the mismatch is phenylketonuria.
resolved as a proper G-C base pair in one · C-G base pair is replaced by T-A at codon
daughter strand and A-T base pair in other 408 of the gene.
daughter strand. · The resulting mRNA is UGG (Tryptophan)
instead of CGG (Arginine).
C. Nonsense Mutation
- A base substitution creates a new STOP codon
(UAA, UAG, or UGA).
B. Transition Mutation - Almost always result in loss of gene function.
- One pyrimidine base is replaced with the other - Ex. UGG (Try)  UGA (Stop)
pyrimidine base or one purine base with the other D. Frameshift Mutation
purine base. - Mutation that shifts the reading frame of the
- The four possible transitions are: codons in the mRNA.
· Pyrimidine  Pyrimidine - Deletions or Insertions in the mRNA sequence
T  C or C  T shifts the phase in which the ribosome reads the
· PurinePurine triplets.
A  G or G  A - Ex. Addition of an Adenine

C. Transversion Mutation
- A pyrimidine base is replaced with a purine base
or the other way around.
- The eight possible transversions are:
· Pyrimidine  Purine
TA TG CA CG

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Types of Mutations 3. INVERSION

Normal – THE ONE BIG FLY HAD ONE RED EYE  A portion in the chromosome is
· Missense – THQ ONE BIG FLY HAD ONE RED reversed and gets inserted back
EYE into the chromosome
· Nonsense – THE ONE BIG ------------------------  Individual is often normal unless
· Frameshift – THE ONE QBI GFL YHA DON ERE inversion breakpoin is in the
DEY middle of a gene or affects the
· Deletion – THE ONE BIG --- HAD ONE RED EYE centromere
· Insertion – THE ONE BIG FLY WET HAD ONE  Types:
RED EYE - Pericentric: encompasses the
· Duplication – THE ONE BIG FLY FLY HAD ONE centromere of the
RED EYE chromosome.
- Paracentric: involves either the short or long arm
CHROMOSOMAL MUTATIONS of the chromosome and does not include the
 Any change or error that occurs within the centromere.
chromosome
 Affects the entirety of the chromosome
 Types:
a. Mutations on the structure of chromosomes
b. Mutations on chromosome number

I. STRUCTURAL CHROMOSOMAL
MUTATIONS
 Usually occurs during any errors in cell division
 Classification:
1. Deletion
2. Duplication
3. Inversion
4. Translocation

1. DELETION
 A part of DNA is not duplicated
or lost during DNA replication
 The deleted region could range
from a mere nucleotide or can
be as large as an entire
chromosome
 Ex. Cri Du Chat, Duchenne
4. TRANSLOCATION
muscular dystrophy, Di
 A fragmented chromosome tends to join with a
George’s syndrome, etc.
non-homologous chromosome
 The newly-formed segment then detaches from the
2. DUPLICATION
chromosome and moves to a new position on
 An extra copy of a region or
another chromosome
regions in the DNA is produced
 Types:
 The extra copy can be located
- Reciprocal Translocation
in its normal location, other
- Robertsonian Translocation
parts of the chromosome, or
even in another chromosome
 Ex. Charcot-Marie-Tooth
disease type I

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4A. RECIPROCAL TRANSLOCATION 1. EUPLOIDY

- Two different chromosomes exchange parts
- Individual is usually normal unless the
translocation break point is in the middle of a
gene.
4B. ROBERTSONIAN TRANSLOCATION
- Two q arms of two different chromosomes come
together but the two p arms lost entirely.
- This results to an overall chromosome number of
45 instead of 46.
- Commonly occurs between chromosome 13/14
and 14/21.
- Ex. Translocation Down Syndrome, Trisomy 13.
 Cells contain correct and complete set of
chromosomes
 Examples include but are not limited to:
- Monoploidy (x)
 One copy of each homolog
- Diploidy (2x)
 Two copies of each homolog.
 Humans are diploid organisms (one set of
chromosomes from each parents).
2. ANEUPLOIDY
 The chromosome number of the new individual is
different from its wild type
- Wild type: most common genotype or phenotype
in a given population
 Typically a result of non-disjunction of
chromosomes during mitosis
- Non-disjunction: Unequal division of
chromosomes during meiosis.
- One gamete has two copies of the same
chromosome whereas the other gamete contains
zero copy of that chromosome.

Non – Disjunction

 As a result, offsprings have either extra or lost

CHROMOSOMAL NUMBER MUTATIONS
chromosomes (in humans having 47 or 45
 “Ploidy” refers to the number of sets of chromosomes instead of 46).
chromosomes in a cell”.
 The naming of aneuploid conditions is based on
 Terms: the chromosome number added or deleted
1. Euploidy A. Monosomy (2n-1)
2. Aneuploidy B. Trisomy (2n+1)
3. Polyploidy C. Tetrasomy (2n+2)
D. Nullisomy (2n-2)

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2C. TETRASOMY/ PENTASOMY

2A. MONOSOMY  2n+2/2n+3
 2n-1  Presence of four or five copies of chromosome,
 Refers to lack of one chromosome of the normal respectively.
complement  Rarely seen in autosomes.
 Ex. Turner Syndrome (45,X or 45,X0)  Tetrasomy/pentasomy of sex chromosomes have
- Female is partly or completely been reported.
missing an X chromosome.
- Affected individuals have short 2D. NULLISOMY
stature, low hairline, abnormal  2n-2
bone development and eye  Lack of both the normal chromosomal pairs.
features, webbed necked, and  Humans with this condition will not survive.
a “cave-in” appearance to the
chest. 3. POLYPLOIDY
 Refers to numerical change in a whole set of
chromosomes.
 An individual bears more than one set of
chromosomes.
 Common phenomenon among plants as well as
certain groups of fish, salamander, frogs, and
leeches.
 Rarely occurs in humans (although it occurs in
highly-differentiated tissues such as liver
parenchyma and heart muscle)
 Occurs as (Humans):
A. Triploidy
B. Tetraploidy

3A. TRIPLOIDY
 3x or 3 sets of chromosomes
- 3 x 23 = 69 chromosomes
2B. TRISOMY
 Majority of triploid conceptions end as a
 2n+1
miscarriage
 Refers to presence of three copies, instead of the
 Those that do survive to term typically die shortly
normal two, of a particular chromosome.
after birth
 Only Trisomy 13 (Patau syndrome), 18 (Edwards
 May be a result of either:
syndrome) and 21 (Down syndrome) are viable.
- Digyny: extra haploid set is from the mother
 Trisomy of sex chromosomes is also possible (47,
- Diandry: extra haploid set is from the father
XXX), (47, XXY) (47, XYY).

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ADVANTAGES OF MUTATIONS
3B. TETRAPLOIDY
 4x or 4 sets of chromosomes
- 4 x 23 = 92 chromosomes
 More rarely diagnosed than triploidy.
 Also end up to miscarriage.

OTHER ABNORMAL CHROMOSOMAL STRUCTURES

 Isochromosomes
- Two identical chromosome arms
- Two p’s or two q’s
 Ring chromosomes
- One end of chromosome attaches to one end
forming a ring due to lost or non-functional
telomeres
 Cannot undergo mitosis successfully.

SUMMARY OF ABBREVIATIONS

1. Survival
- Help some individuals of the population to adapt to their
environment.
- Important force in evolution because they balance out
frequency of allelles present in a population.
- Examples:
o Malaria resistance, lactose intolerance
2. Diversity
- Without genetic diversity, some of the fundamental
mechanisms of evolutionary change cannot and
continue to operate.

DISADVANTAGES OF MUTATIONS
1. Genetic Disorders
- Mutations can cause a wide variety of genetic disorders
which can be highly devastating
2. Other diseases
- Aside from inheritable disorders, ceratain mutations can
also bring about the onset of other diseases (e.g. Lung,
breast, and bladder cancer)