Mutations: origin, patterns and implications Flashcards by Joe Rowlands

What is a mutation?

A heritable change in the base sequence of DNA

May affect the structure and function of a protein when it occurs within a gene

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What are gene mutations?

Relatively small change in DNA structure that affects a single gene

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What are chromosome mutations?

Changes in chromosome structure (aneuploidy)

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What are genome mutations?

Changes in chromosome number (translocation/inversion)

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What are spontaneous mutations?

Result from abnormalities in cellular/biological processes

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Give some examples of spontaneous mutations

Errors in DNA replication
Aberrant recombination
Aberrant segregation
Transposable elements
Depurination
Deaminations
Tautomeric shifts
Toxic metabolic products

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What is depurination?

The removal of a purine (guanine or adenine) from the DNA.
This is termed an apurinic site
If the repair system fails, then a mutation may result during rounds of DNA replication

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What are induced mutations?

Mutations caused by environmental agents:
Physical
Chemical
Biological/infectious

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What are mutagens?

Agents that are known to alter DNA structure

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What is a teratogen?

Any environmental factor that can produce a permanent abnormality in structure or function, restriction of growth, or death of the embryo or fetus

(eg. sodium valproate)

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What is a carcinogen?

Any agent capable of causing cancer in humans or animals.

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What is a genotoxic and non-genotoxic carcinogen?

Genotoxic - if the mutagen binds covalently to DNA

non-genotoxic - non DNA reactive, metabolic effects

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What are epigenetic carcinogens?

Do not damage DNA directly.

may induce expression of enzymes that metabolise carcinogens to DNA reactive forms.

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What are clastogens?

Mutagen that can cause breaks in chromosomes leading to sections of the chromosome being deleted, added or rearranged

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What are Aneugens?

Mutagen that causes a daughter cells to have an abnormal number of chromosomes or aneuploidy

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What is the Ames test?

Biological assay which uses bacteria to assess the mutagenic (and therefore carcinogenic) potential of chemical compounds.

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Why is the Ames test used?

Often used as one of the initial screes for potential drugs to indicate possible carcinogens.

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What are the main physical mutagens?

Ionising radiation
Non-ionising radiation
Heat

What are some ionising radiation mutagens?

X-rays / gamma rays / corpuscular radiation.

Has short wavelengths and high energy so they can penetrate deeply into biological molecules creating chemically reactive molecules (free radials) that break covalent bonds.

What mutations can ionising radiation cause?

Damage to base and sugar residues
Base deletions
Oxidise bases
Single nicks in DNA strands
Cross-linking
Chromosomal breaks

What type of non-ionising radiation is a mutagen?

UV light.

Has less energy and cannot penetrate as deeply into biological molecules.

What does UV radiation cause?

formation of cross-linked thymine dimers.

Thymine dimers may cause mutations when that DNA strand is replicated.

What are the different types of chemical mutagens?

Base analogues
Base altering chemicals
Intercalating agents
Agents altering DNA structures

What are base analogue mutagens?

Structurally resemble purines and pyrimidines and may incorporate into DNA in place of normal bases
(eg. Bromouracil will incorporate into DNA and pair with A due to being similar to thymine residues)

What are base modifying mutagens?

Chemicals that alter structure and pairing properties of bases

What are deaminating agents?

base modifying mutagens: Nitrous acid formed by digestion of nitrites in food, causing C to U, C to T and A to hypoxanthine deaminations leading to baes transitions

What are Hydroxylating agents?

Base modifying mutagens: | add OH- groups to C

What are alkylating agents?

Base modifying mutagens: | add methyl or ethyl groups to bases

What are intercalating agents?

Plate-like, multiple ringed molecules which interact with DNA bases and insert between them. This causes stretching of DNA duplex causing DNA polymerase during replication to insert bases resulting in frameshifts.

Give some examples of intercalating agents

Acridine orange, Proflavine, ethidium bromide

What are transposon mutagens?

Insert into DNA and disrupts the gene structure

What are Viral mutagens?

virus DNA may be inserted into the genome and disrupt genetic function.

What is aetiology?

the cause, set of causes or manner of causation for a disease or condition.

What are bacterial mutagens?

May cause DNA damage and reduce the efficiency of DNA repair systems, therefore increasing mutations rate (eg. Helicobacter Pylori)

What are mutational signatures?

Mutational signatures are characteristic combinations of mutation types arising from specific mutagenesis processes

What are germline mutations?

Mutations that occur directly in a sperm or egg cell, or in one of their precursor cells. This mutation will be inherited

What are somatic mutations?

Mutations that occur directly in a body cell or in one of its precursor cells. This mutation will not be inherited

What is a polymorphism?

Genetic alteration that occur in more than 1% of the population and therefore are considered a normal variation in the DNA

What are polymorphisms responsible for?

Responsible for many of the normal differences between people such as eye colour, hair colour and blood type.

How do mutations correspond with genetic variation?

Mutations provide allelic variation. | For every gene there are many different alleles in a population thus the combination makes you unique.

Define evolution

Genetic change in a population over time.

What example is there for the duplication of genes?

Ancestral Globin gene was duplicated into alpha and beta types and thus later transposed to different chromosomes and followed further subsequent duplications and mutations

Who has a higher mutation rate?

Men have a higher substitution mutation rate Females have a higher deletion mutation rates