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DR. J IBRIL IHSAN MUNZALIREGISTRAR, DEPT OF HISTOPATHOLOGY

NHA

Genetic mutation

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Outline

IntroductionA. What are genes?B. What are mutations?C. What does genetic mutation mean?

Types of genetic mutation

Causes of genetic mutation

Diseases caused by genetic mutation

Diagnosis/Treatment Conclusion

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Genes

A gene is a segment of DNA that encodes a specific peptide or protein.

DNA is the genetic material within the nucleus or mitochondria where an individual’s genetic information is stored.

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Nucleotides

DNA is composed of

sequence of nucleotides

Each nucleotide is made up

of three components.

There are four types of

nucleotide bases.

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DNA

The nucleotides are covalently bound to each

other through phosphodiester bonds to form a

linear structure.

Nucleotides are non covalently bound to each

other through hydrogen bonds forming a

double helix.

DNA polymers combine with proteins termed

histones to form nucleosomes. These fibers

form very compact structures known as

chromosomes.

The order or sequence of the nucleotides in

the DNA chain is the genetic code present

within the cell.

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Protein synthesis Genetic code

Protein synthesis

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DNA Replication

Replication of genetic material occurs during the S phase of the cell cycle

DNA polymerase needs a pre-existing DNA to form two new double bond strands identical to the original strand

Every new double strand is semi-conservative (half old and half new)

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Genetic mutation

Genetic mutation is a permanent heritable change in a gene of an individual.

It leads to formation of abnormal proteins or non-production of proteins.

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Mutations

Mutations occurs at a frequency of about 1 in every 1 billion base pairs.

Everybody has about 6 mutations in each cell in their body.

May occur in either introns or exons or even mitochodrial genes.

Mutations could be germline or somatic

It could be deleterious or beneficial.

May follow classic Mendelian patterns or non classic mode of inheritance.

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Causes of genetic mutation

Could occur spontaneously or could be acquired

Spontaneous mutations arise during normal DNA replication as DNA polymerase may make mistakes during replication.

If DNA errors are not repaired, mutations arise.

Other spontaneous types of DNA damage include tautameric shifts, alkylation, oxidation or hydrolysis

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Examples of base damage

These types of damages cause the chemical structure of the bases to change.

They may change to another type of base.

They then “mis pair” with incorrect bases.

This leads to abnormality in the reading frame.

Hydroxylation

Tautameric shift

Oxidation

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Acquired causes

Acquired causes include drugs, radiation, viruses.

Drugs may cause alkylation, oxidation etc

Ionizing radiation causes breaks and cross linking

Viruses may cause degradation of certain genes.

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Types of genetic mutation

1. Point mutations: This is the substitution of one

nucleotide with another changing the sequence of the

codon. This could lead to a misense, nonsense or even

synonymous mutation.

2. Frame shift mutations: This is when there is insertion

or deletion of a single base or a number of bases not in

the multitude of 3 causing alteration of the reading

frame.

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Types of mutations

3. Deletions of a codon/three-base deletion: Leads to

deletion of an amino acid in a protein thus the protein is

defective eg cystic fibrosis

4. Large deletions: Could also occur leading to deletion of

the whole gene leading to absent protein or hybrid

protein.

Trinucleotide repeats

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Point mutation: Nonsense mutation

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Missense mutation

Sickle cell anaemia

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Frameshift mutation

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Frame shift mutation

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Three base deletion

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Diagnosis/Treatment

Biochemical testing of affected protein.

PCR can also be used to amplify and identify the affected gene/genes .

There are currently no “cures” for genetic disorders,.

Gene therapy is being looked into: It may be possible to replace a defective gene with a normal copy.

Second, the function of an abnormal gene may be abrogated by administering anti-sense RNA or by RNA-mediated interference

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Conclusion

Genetic mutations are important causes of both heritable and acquired human diseases.

They usually affect genes with large effects.

Environmental factors such as chemicals, drugs and radiations are important causes of radiation.

Currently, genetic mutations represent a group of diseases, a large extent to which are still unknown and treatment of which is still under research.

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THANK YOU VERY MUCH.