This document provides an overview of gene and chromosomal mutations. It defines mutations as changes in genes or chromosomes that are passed down to offspring. There are two main types of mutations: gene mutations, which alter DNA sequences within a gene, and chromosomal mutations, which involve changes in chromosome structure or number. The document outlines several specific types of gene mutations, including point mutations, frameshift mutations, insertions, and deletions. It also describes different types of chromosomal mutations, such as duplications, inversions, translocations, and changes in chromosome number. The goal is to help students understand the various ways mutations can occur in human genes and chromosomes.

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
53
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54. MUTATION
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Topics