Chapt 08

GENERAL BIOLOGY

SCHOOL OF MLTFACULTY OF HEALTH SCIENCE

PREPARED BY:MANEGA

HDL 121MUTATION

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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

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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

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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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1.1. Definition

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Types of mutation

Gene mutationChromosomal mutation

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1.1. Definition

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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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1.2. Gene Mutation

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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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1.2. Gene Mutation

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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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1.2. Gene Mutation

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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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1.2. Gene Mutation

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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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1.2.1 Types of gene mutation

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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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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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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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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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Insertion & Deletion

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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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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

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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

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1.3. Chromosomal Mutation

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Chromosomal mutationDuplicationDeletionTranslocation Inversion

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1.3. Chromosomal Mutation

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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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1.3.1 Types of chromosomal mutation

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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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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

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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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(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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4. Translocation

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Reciprocal translocations

Two non-homologous chromosomes

break and exchange fragments

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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)

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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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1.1. Chromosome (definition)

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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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1.1. Chromosome (definition)

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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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1.1.1 Structure of normal chromosome

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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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1.1.2 Components of chromosome

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1.1.3 Classfication

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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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1.1.4 Normal Karyotype

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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

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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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Human Female

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http://www.pathology.washington.edu/galleries/Cytogallery/cytogallery.html

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Human Male

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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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1.2. Chromosomal abnormality

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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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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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Down Syndrome karyotype

04/10/2023 46

1.2.1 Clinical application

http://upload.wikimedia.org/wikipedia/commons/1/11/Down_Syndrome_Karyotype.png

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Down Syndrome

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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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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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Turner Syndrome

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Turner Syndrome Karyotype

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Klinefelter SyndromeMen inherit an extra X chromosome

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THANK YOU

Chapt 08

Education

gene mutation gene mutations

gene mutation thatmay

type of mutation

missense mutation

actual mutation

types of point mutation

gene coding

gene mutationacquired