1. GENERAL BIOLOGY
HDL 121
MUTATION
PREPARED BY:MANEGA
SCHOOL OF MLT
FACULTY OF HEALTH SCIENCE

2. MUTATION
Learning Outcomes
After completing this lecture, students will be able to:
(a) Define gene mutation & chromosomal mutation
(b) List the type of gene mutation & chromosomal
mutation
(c) Describe each type of gene & chromosomal
mutation
(d) Develop an understanding of the mutations in
humans’ gene & chromosome
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Topics
© 2010 Cosmopoint

3. MUTATION
Topic Outlines
1.1. Definition
1.2. Gene Mutation
1.2.1 Types of gene mutation
1.3. Chromosomal Mutation
1.3.1 Types of chromosomal mutation
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© 2010 Cosmopoint

4. MUTATION
1.1. Definition
Introduction
Mutation: changes in genes or chromosomes that is
recorded durably & passed on to the offspring.
Result in the change of the shape of a protein  protein
cannot function well
Mutation can be caused by
(a) copying errors in the genetic material during
cell division (spontaneous mutation) – point
mutation + frameshift mutation
(b) exposure to ultraviolet or ionizing radiation,
chemical mutagens or viruses (induced mutation)
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5. MUTATION
1.1. Definition
Types of mutation
Gene mutation
Chromosomal mutation
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6. MUTATION
1.2. Gene Mutation
Gene Mutation
A permanent change in the DNA / nucleotide base
sequence that makes up a gene.
The change of a single nucleotide base pair is called
point mutation.
Types of point mutation:
(a) base substitution
(b) frameshift mutation
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7. MUTATION
1.2. Gene Mutation
Gene mutations occur in two ways:
(a) They can be inherited from a parent or acquired
during a person’s lifetime
(b) Mutations that are passed from parent to child are
called hereditary mutations / germ line mutations
(because they are present in the egg & sperm
cells, which are also called germ cells)
This type of mutation is present throughout a person’s life
in virtually every cell in the body
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8. MUTATION
1.2. Gene Mutation
Mutations that occur only in an egg / sperm cell, or
those that occur just after fertilization, are called new
(de novo) mutations.
De novo mutations may explain genetic disorders in
which an affected child has a mutation in every
cell, but has no family history of the disorder
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9. MUTATION
1.2. Gene Mutation
Acquired (or somatic) mutations occur in the DNA of
individual cells at some time during a person’s life.
These changes can be caused by environmental factors
eg. ultraviolet radiation from the sun, or can occur if a
mistake is made as DNA copies itself during cell
division.
Acquired mutations in somatic cells (cells other than
sperm & egg cells) cannot be passed on to the next
generation
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10. MUTATION
1.2.1 Types of gene mutation
When a mutation occurs within a gene, the protein
encoded by the gene is often altered.
This alteration may produce a visible change in the
displayed characteristics (phenotype) of the organism
studied.
The actual mutation itself (genotype) is invisible to the
naked eye.
Structurally, mutations can be classified as
(a) Small-scale / Gene mutations, eg affecting a small
gene is one or a few nucleotides
(b) Large-scale / chromosome mutations in
chromosomal structure
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11. MUTATION
1.2.1 Types of gene mutation
1. Point mutation
Often caused by chemicals / malfunction of DNA
replication, exchange a single nucleotide for
another (base substitutions)
Most common is
(a) Transition that exchanges a purine for a purine
(A G) or a pyrimidine for a pyrimidine
(C  T)
(b) Transversion, which exchanges a purine for a
pyrimidine or a pyrimidine for a purine
(C/T  A/G)
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12. MUTATION
1.2.1 Types of gene mutation
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13. MUTATION
1.2.1 Types of gene mutation
Base substitutions occurring in protein-coding regions
affect the expressed protein except when the change is
in the 3rd base of a codon.
Silent / synonymous mutation: gene mutation that
may not cause any amino acid change in the expressed
protein
Non-synonymous mutation:
(a) Missense mutation – modifies the affected
codon, specifying an amino acid different from the one
previously encoded
(b) Nonsense mutation – changes a codon into one
the three termination codon TAG, TAA or TGA
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14. MUTATION
1.2.1 Types of gene mutation
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15. MUTATION
1.2.1 Types of gene mutation
Example
 Sickle cell anaemia
 Autosomal recessive disease caused by a point mutation in the
haemoglobin β gene (HBB) on the chromosome
 Mutation results in the production of structurally abnormal
haemoglobin, known as HbS
 Amino acid glutamate is replaced by valine at position 6 of the β
subunit  RBC distorted into sickle shape.
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16. MUTATION
1.2.1 Types of gene mutation
2. Frameshift mutation
Insertion
- add one or more extra nucleotides into the DNA.
- causing an alteration of the reading frame & producing
an entirely new sequence of amino acid
- if base insertion occurs in a gene coding for an
enzyme, the resultant enzyme will lose its activity
Deletion
- remove one or more nucleotides from the DNA.
- like insertions, these mutations can alter the reading
frame of the gene.
- they are generally irreversible
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17. MUTATION
1.2.1 Types of gene mutation
Insertion & Deletion
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18. MUTATION
1.2.1 Types of gene mutation
3(a): Protein that may not have normal activity
3(b): addition of a base produces a +1 frameshift, removing
a pre-existing stop signal & giving rise to an
elongated protein.
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19. MUTATION
1.2.1 Types of gene mutation
Base inversion
Involves the reversal of a portion of a nucleotide sequence
ABCDEFGHI
ABCFEDGHI
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20. MUTATION
1.3. Chromosomal Mutation
Chromosomal mutation
Definition: alterations in the number / structure of the
chromosome
It can be passed to the offsprings if they occur in cells
that become gametes
This can increase variation among the offspring
Two kinds of chromosomal mutation
(a) Chromosomal aberration
(b) Chromosomal number alteration
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21. MUTATION
1.3. Chromosomal Mutation
Chromosomal mutation
Duplication
Deletion
Translocation
Inversion
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22. MUTATION
1.3.1 Types of chromosomal mutation
1. Duplication
Leading to multiple copies of all chromosomal regions
It involves the insertion of an extra copy of a region of
the chromosome into
a neighbouring position
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23. MUTATION
1.3.1 Types of chromosomal mutation
2. Deletion
2 types
(a) large chromosomal regions, leading to loss of the
genes within those regions
(b) intra-chromosomal deletion that removes a
segment of DNA from a single chromosome
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24. MUTATION
1.3.1 Types of chromosomal mutation
Chromosome breaks often heal spontaneously, but a
break that fails to heal may cause the loss of an
essential part of the gene complement
This loss of genetic material is called gene deletion
A germ cell thus affected may be capable of taking part
in the fertilization process, but the resulting zygote may
be incapable of full development & may therefore die in
an embryonic state
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25. MUTATION
1.3.1 Types of chromosomal mutation
3. Inversion
A type of mutation where the structure of the
chromosome is reversed, or inverted.
It results from a segment that has broken out of the
chromosome & rejoins at the same site but with inverted
direction.
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26. MUTATION
1.3.1 Types of chromosomal mutation
(a) a chromosomal inversion has a set of genes inverted. The letters
represent genes along the chromosomes.
(b) Recombination in a heterozygote can produce chromosomes that
lack some genes and have others in double dose. These forms are
probably selected against.
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27. MUTATION
1.3.1 Types of chromosomal mutation
4. Translocation
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28. MUTATION
1.3.1 Types of chromosomal mutation
Reciprocal translocations
Two non-homologous chromosomes
break and exchange fragments
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29. MUTATION
1.3.1 Types of chromosomal mutation
Centric Fusions Translocation
A centric fusion is a translocation in which the
centromeres of two acrocentric chromosomes fuse to
generate one large metacentric chromosome
They are also often called Robertsonian translocations
The karyotype of an individual carrying a centric fusion
has one less than the normal number of chromosomes
DML 202 General Biology & Human
11/16/2011 Genetics (Chapter 13: 29
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Mutation)

30. MUTATION
1.3.1 Types of chromosomal mutation
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31. MUTATION
1.1. Chromosome (definition)
Introduction – Chromosome
Organised structures of DNA & proteins that are found in
cells
Contain a single continuous piece of DNA, which contains
many genes, regulatory elements & other nucleotide
sequences.
Each chromosome has one centromere, with one or two
arms projecting from the centromere, although under most
circumstances theses arms are not visible as such.
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32. MUTATION
1.1. Chromosome (definition)
In the nuclear chromosomes of eukaryotes, the
uncondensed DNA exists in a semi-ordered
structure, where it is wrapped around histones
(structural proteins), forming a composite material
called chromatin.
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33. MUTATION
1.1.1 Structure of normal chromosome
Structure of Chromosome
Each chromatid is made up of at least one molecule of
DNA. This is the result of replication
Each of the 2 identical molecules becomes a chromatid &
they are attached together by a centromere
During prophase, each DNA molecule wound around a
group of 8 histone molecules forming a complex unit called
nucleosome.
During interphase, a certain amount of DNA does form
nucleosomes called euchromatin, which contains genes
that are activated
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34. MUTATION
1.1.2 Components of chromosome
6 such nucleosomes may coil regularly to form a
secondary structure, which may be tertiary coiled to
become the compact chromatid
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35. MUTATION
1.1.3 Classfication
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36. MUTATION
1.1.4 Normal Karyotype
Karyotype
Pictures of chromosomes cut out from a
microphotograph of a cell & rearranged into
homologous pairs according to size & other physical
characteristics.
The standardized arrangement of karyotypes allows
researchers to discover if an individual is a male or
female & if he/she has any gross chromosomal
abnormalities.
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37. MUTATION
1.1.4 Normal Karyotype
Human have 46 chromosomes or 23 pairs in each cell
The member of a pair have the same
size, shape, location of centromere & banding pattern
Sex chromosomes contain genes that determine sex
The larger chromosome of this pair is X; smaller is Y
Autosome: non-sex related chromosomes
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38. MUTATION
1.1.4 Normal Karyotype
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39. MUTATION
1.1.4 Normal Karyotype
 Group A: chromosomes 1-3 are largest with median centromere
 Group B: chromosomes 4-5 are large with sub-median centromere
 Group C: chromosomes 6-12 are medium sized with sub-median
centromere
 Group D: chromosomes 13-15 are medium sized with acrocentric
centromere
 Group E: chromosomes 16-18 are short with median or sub-median
centromere
 Group F: chromosomes 19-20 are short with median centromere
 Group G: chromosomes 21-22 are very short with acrocentric
centromere; chromosome X is similar to group C & Y is similar to
group G.
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40. MUTATION
1.1.4 Normal Karyotype
Human Female
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41. MUTATION
1.1.4 Normal Karyotype
Human Male
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42. MUTATION
1.1.4 Normal Karyotype
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43. MUTATION
1.2. Chromosomal abnormality
Chromosomal abnormalities
Usually occur when there is an error in cell division
following meiosis or mitosis
There are two major categories of chromosomal
abnormalities:
(a) irregular number of chromosomes (numerical)
(b) structural modification in a chromosome
(structural)
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44. MUTATION
1.2. Chromosomal abnormality
Numerical abnormalities
Aneuploidy: presence or absence of a single extra
autosomal chromosome; describes a numerical change
in part of the genome, usually a change in the dosage of
a single chromosome.
Polyploidy: a state where the number of set of
chromosomes exceeds the diploid number by a multiple
of n; happens due to the failure of the spindle fibers in
mitosis/meoisis to segregate chromosomes into separate
groups.
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45. MUTATION
1.2. Chromosomal abnormality
Aneuploidy
When an individual is missing either a chromosome from a
pair (monosomy: 2n – 1) or has more than two
chromosomes of a pair (trisomy: 2n + 1)
Eg. Down Syndrome, also known as Trisomy 21 (an
individual with Down Syndrome has three copies of
chromosome 21, rather than two)
Eg. of monosomy: Turner syndrome where the individual
is born with only one sex chromosome, an X.
Happens when homologous chromosomes fail to
segregate properly during meiosis (non-disjunction)
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46. MUTATION
1.2.1 Clinical application
Down Syndrome karyotype
11/16/2011 46
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47. MUTATION
1.2.1 Clinical application
Down Syndrome
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48. MUTATION
1.2.1 Clinical application
Down syndrome is associated with some impairment of
cognitive ability & physical growth as well as facial
appearance. Down syndrome can be identified during
pregnancy or at birth.
Symptoms: muscle hypotonia (poor muscle tone), a
protruding tongue (due to small oral cavity, & an
enlarged tongue near the tonsils), a short neck, white
spots on the iris known as Brushfield spots
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49. MUTATION
1.2.1 Clinical application
Turner Syndrome
Instead of the normal XX sex chromosomes for a
female, only one X chromosome is present & fully
functional; in rarer cases a second X chromosome is
present but abnormal.
A normal female karyotype is labelled 46, XX;
individuals with Turner syndrome are 45, X. In Turner
syndrome, female sexual characteristics are present
but generally underdeveloped.
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50. MUTATION
1.2.1 Clinical application
Turner Syndrome
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51. MUTATION
1.2.1 Clinical application
Turner Syndrome Karyotype
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52. MUTATION
1.2.1 Clinical application
Klinefelter Syndrome
Men inherit an extra X chromosome
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53. MUTATION
1.2.1 Clinical application
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54. MUTATION
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Topics