Mutations are changes in genes or chromosomes that are passed on to offspring. There are two main types: gene mutations, which alter DNA sequences within a gene, and chromosomal mutations, which involve changes to chromosomes. Gene mutations include point mutations like substitutions of single nucleotide bases and frameshift mutations from insertions or deletions of bases. Chromosomal mutations involve changes in chromosome number, such as duplications, or structure, including deletions, inversions, and translocations of chromosomal segments. Understanding genetic mutations is important for developing knowledge of their effects in humans.
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)
4
Slide 4 of 10
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
) 6
Slide 6 of 10
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
7
Slide 7 of 10
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
8
Slide 8 of 10
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
9
Slide 9 of 10
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
10
Slide 10 of 10
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)
11
Slide 11 of 10
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
13
Slide 13 of 10
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.
15
Slide 15 of 10
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
16
Slide 16 of 10
17. MUTATION
1.2.1 Types of gene mutation
Insertion & Deletion
17
Slide 17 of 10
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.
18
Slide 18 of 10
19. MUTATION
1.2.1 Types of gene mutation
Base inversion
Involves the reversal of a portion of a nucleotide sequence
ABCDEFGHI
ABCFEDGHI
19
Slide 19 of 10
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
20
Slide 20 of 10
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
22
Slide 22 of 10
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
23
Slide 23 of 10
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
24
Slide 24 of 10
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.
25
Slide 25 of 10
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.
26
Slide 26 of 10
28. MUTATION
1.3.1 Types of chromosomal mutation
Reciprocal translocations
Two non-homologous chromosomes
break and exchange fragments
28
Slide 28 of 10
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
Slide 29 of 10
Mutation)
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.
31
Slide 31 of 10
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.
32
Slide 32 of 10
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
33
Slide 33 of 10
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
34
Slide 34 of 10
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.
36
Slide 36 of 10
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
37
Slide 37 of 10
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.
39
Slide 39 of 10
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)
43
Slide 43 of 10
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.
44
Slide 44 of 10
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)
45
Slide 45 of 10
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
48
Slide 48 of 10
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.
) 49
Slide 49 of 10