Chapt 08
-
Upload
uthaya-kumar -
Category
Technology
-
view
345 -
download
0
description
Transcript of Chapt 08
GENERAL BIOLOGY
SCHOOL OF MLTFACULTY OF HEALTH SCIENCE
PREPARED BY:MANEGA
HDL 121MUTATION
MUTATION
Slide 2 of 10
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
Topics© 2010 Cosmopoint
MUTATION
Slide 3 of 10
Topic Outlines
1.1. Definition
1.2. Gene Mutation1.2.1 Types of gene mutation
1.3. Chromosomal Mutation1.3.1 Types of chromosomal mutation
© 2010 Cosmopoint
MUTATION
Slide 4 of 10
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
1.1. Definition
MUTATION
Slide 5 of 10
Types of mutation
Gene mutationChromosomal mutation
5
1.1. Definition
MUTATION
Slide 6 of 10
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
1.2. Gene Mutation
MUTATION
Slide 7 of 10
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
1.2. Gene Mutation
MUTATION
Slide 8 of 10
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
1.2. Gene Mutation
MUTATION
Slide 9 of 10
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
1.2. Gene Mutation
MUTATION
Slide 10 of 10
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
1.2.1 Types of gene mutation
MUTATION
Slide 11 of 10
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
1.2.1 Types of gene mutation
MUTATION
Slide 12 of 1012
1.2.1 Types of gene mutation
MUTATION
Slide 13 of 10
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
1.2.1 Types of gene mutation
MUTATION
Slide 14 of 1014
1.2.1 Types of gene mutation
MUTATION
Slide 15 of 10
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
1.2.1 Types of gene mutation
MUTATION
Slide 16 of 10
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
1.2.1 Types of gene mutation
MUTATION
Slide 17 of 10
Insertion & Deletion
17
1.2.1 Types of gene mutation
MUTATION
Slide 18 of 10
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
1.2.1 Types of gene mutation
MUTATION
Slide 19 of 10
Base inversion Involves the reversal of a portion of a nucleotide sequence
A B C D E F G H I
A B C F E D G H I
19
1.2.1 Types of gene mutation
MUTATION
Slide 20 of 10
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 offspringTwo kinds of chromosomal mutation
(a) Chromosomal aberration
(b) Chromosomal number alteration
20
1.3. Chromosomal Mutation
MUTATION
Slide 21 of 10
Chromosomal mutationDuplicationDeletionTranslocation Inversion
21
1.3. Chromosomal Mutation
MUTATION
Slide 22 of 10
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
1.3.1 Types of chromosomal mutation
MUTATION
Slide 23 of 10
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
1.3.1 Types of chromosomal mutation
MUTATION
Slide 24 of 10
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 deletionA 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
1.3.1 Types of chromosomal mutation
MUTATION
Slide 25 of 10
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
1.3.1 Types of chromosomal mutation
MUTATION
Slide 26 of 10
(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
1.3.1 Types of chromosomal mutation
MUTATION
Slide 27 of 10
4. Translocation
27
1.3.1 Types of chromosomal mutation
MUTATION
Slide 28 of 10
Reciprocal translocations
Two non-homologous chromosomes
break and exchange fragments
28
1.3.1 Types of chromosomal mutation
MUTATION
Slide 29 of 10
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 translocationsThe karyotype of an individual carrying a centric fusion
has one less than the normal number of chromosomes
04/10/2023DML 202 General Biology & Human
Genetics (Chapter 13: Mutation)
29
1.3.1 Types of chromosomal mutation
MUTATION
Slide 30 of 1030
1.3.1 Types of chromosomal mutation
MUTATION
Slide 31 of 10
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
1.1. Chromosome (definition)
MUTATION
Slide 32 of 10
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
1.1. Chromosome (definition)
MUTATION
Slide 33 of 10
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
1.1.1 Structure of normal chromosome
MUTATION
Slide 34 of 10
6 such nucleosomes may coil regularly to form a secondary structure, which may be tertiary coiled to become the compact chromatid
34
1.1.2 Components of chromosome
MUTATION
Slide 35 of 1035
1.1.3 Classfication
MUTATION
Slide 36 of 10
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
1.1.4 Normal Karyotype
MUTATION
Slide 37 of 10
Human have 46 chromosomes or 23 pairs in each cellThe member of a pair have the same size, shape,
location of centromere & banding patternSex chromosomes contain genes that determine sexThe larger chromosome of this pair is X; smaller is YAutosome: non-sex related chromosomes
37
1.1.4 Normal Karyotype
MUTATION
Slide 38 of 1038
1.1.4 Normal Karyotype
MUTATION
Slide 39 of 10
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
1.1.4 Normal Karyotype
MUTATION
Slide 40 of 10
Human Female
40
1.1.4 Normal Karyotype
MUTATION
Slide 41 of 10
Human Male
41
1.1.4 Normal Karyotype
MUTATION
Slide 42 of 1042
1.1.4 Normal Karyotype
MUTATION
Slide 43 of 10
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
1.2. Chromosomal abnormality
MUTATION
Slide 44 of 10
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
1.2. Chromosomal abnormality
MUTATION
Slide 45 of 10
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
1.2. Chromosomal abnormality
MUTATION
Slide 46 of 10
Down Syndrome karyotype
04/10/2023 46
1.2.1 Clinical application
MUTATION
Slide 47 of 10
Down Syndrome
47
1.2.1 Clinical application
MUTATION
Slide 48 of 10
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
1.2.1 Clinical application
MUTATION
Slide 49 of 10
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
1.2.1 Clinical application
MUTATION
Slide 50 of 10
Turner Syndrome
50
1.2.1 Clinical application
MUTATION
Slide 51 of 10
Turner Syndrome Karyotype
51
1.2.1 Clinical application
MUTATION
Slide 52 of 10
Klinefelter SyndromeMen inherit an extra X chromosome
) 52
1.2.1 Clinical application
MUTATION
Slide 53 of 1053
1.2.1 Clinical application
MUTATION
Slide 54 of 10Topics
THANK YOU