14. Mutation Flashcards by Farha Hamza

What is mutation?

a change of the nucleotide sequence which results in a heritable alteration in a gene or chromosome

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What is mutagenesis?

the process of mutation generation

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Give an example of a spontaneous mutation

Spontaneous deamination - cytosine to uracil

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What are the 3 types of sources that result in defective or error-prone DNA repair and ultimately mutations?

Exogenous sources
Spontaneous events
Endogenous sources

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What does endogenous mean?

Endogenous substances and processes are those that originate from within a system such as an organism, tissue, or cell

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Give 2 types of endogenous sources that result in a mutation

DNA replication defects

2. Transposable elements

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Is the gene activated or inactivated when a transposable element leaves?

Activated

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Is the gene activated or inactivated when the transposable element moves in?

Inactivated

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What is affected when transposable elements go into regulatory regions such as promoter regions?

They change WHEN a gene is activated

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How does the length of a gene effect the affect of transposable elements?

The longer the gene, the more likely that it will be activated or inactivated by transposable elements

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Are mutations good or bad?

may or may not cause a phenotypic change
may be ‘good’ or ‘bad’
a source of genome variation
a driving force of evolution
may cause disease

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What are single nucleotide polymorphisms(SNP)

A single-nucleotide polymorphism (SNP, pronounced snip) is a DNA sequence variation occurring when a single nucleotide in the genome differs between members of a species or paired chromosomes in an individual.

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What is anonymous SNP?

When the SNP has no known efffect

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What is non-coding SNP?

When the SNP is outside a gene

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What is coding SNP?

When the SNP is inside a gene

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What are the 6 types of mutations?

Substitution
Deletion
Insertion
Duplication
Inversion
Translocation

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In transcription, what direction is DNA read in and what direction is mRNA synthesis?

DNA is read 3’ to 5’

mRNA synthesis 5’ to 3’

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In translation, what direction is mRNA read in and what direction is polypeptide synthesis?

mRNA is read 5’ to 3’ polypeptide synthesis N to C

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In single nucleotide changes, what is transition?

Change to same type of base:

purine to purine (A G ) pyrimidine to pyrimidine (T C)

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In single nucleotide changes, what is transversion?

Change to different type of base.

purine to pyrimidine or vice versa (A/G C/T)

What are the possible effects of single nucleotide changes?

change gene product (polypeptide or RNA)
change the amount of gene product
change the polypeptide length
do not have an effect

What causes sickle cell anaemia?

> Mutation in codon 7 of HBB
Base substitution mutation (missense)
One amino Acid change (the 6th amino acid because the first one is MET)
Glutamate —> Valine

What are transposable elements and how do they cause mutations?

specific DNA sequences (>1 gene)
supernumerary (many copies)
always contained within other DNA molecule
move (transpose) as a discrete unit
move (transpose) to random sites
ubiquitous - all species have them
may insertionally inactivate genes or change gene expresssion

What are missense mutations?

When a base substitution results in a change in the amino acid the gene codes for

What are nonsense mutations?

When t=a base substitution results in the gene coding for a stop codon

What mutations can change the polypeptide length?

frameshift mutation OR mutation of stop codon OR nonsense mutation

What are synonymous mutations?

mutations that have no effect because the same amino acid is coded for- silent mutations

What are the 3 mutations that base substitution cause?

synonymous OR missense OR nonsense mutation

What type of mutation do insertion and deletion of nucleotide bases result in?

Frameshift

What mutations can change the gene product?

missense mutation / | non-synonymous mutation

What mutations do not have an effect?

silent or neutral | mutation / synonymous mutation

What mutations can change the amount of gene product?

mutations affecting regulatory sequences: alter promoter activity alter translation initiation at AUG prevent mRNA splicing reduce mRNA stability

What mutations occur at the micro level?

Deletion Insertion Substitution

What mutations occurs at the macro level?

* Deletions (including microdeletions) * Duplications * Inversions (paracentric and pericentric) * Substitutions / Insertions * Translocations (reciprocal & Robertsonian) * Isochromosomes * Ring chromosomes * Marker chromosomes

What is Robertsonian translocation?

* when Two different chromosomes where p arm is very small and q arm is very long break at the centromere. * The two q arms fuse at the centromere to form a large chromosome * The two p arms are lost * This means that the individual has 45 chromosomes instead of 46 * There is no phenotypic effect as the p arms are lost and the q arms act as a single chromosome

What is polyploidy?

Gain of extra haploid set of chromosomes (3n=69)

What is the most common cause of polyploidy?

polyspermy- two sperm fuse with one egg

What is aneuploidy?

loss or gain of whole chromosomes

What is the cause of aneuploidy?

caused by non-disjunction in meiosis

Give 4 examples of trisomies

Down syndrome 47,+21; Patau 47,+13; Edwards 47,+18 Klinefelter syndrome 47,XXY

Why are individuals with Klinefelter syndrome phenotypically normally male?

They have XXY but one X is always inactivated

Give an example of a monosomy that is viable

Turner syndrome 45,X

What is mosaicism

presence of two or more cell lines in an individual (throughout the body or tissue- specific)

What causes mosaicism?

caused by non-disjunction in mitosis

How do we test for chromosomal abnormalities?

Cytogenetic testing: • Cytogenetic analysis (karyotyping e.g. 46,XY,inv(7)(p11.2q11.23) = male with chr 7 inversion • Fluorescent in situ hybridisation (FISH) • Microarray hybridisation • DNA sequencing (and other molecular techniques)

Why would we do cytogenetic testing?

• Accurate diagnosis and prognosis of clinical problems (e.g. identify a syndrome, account for a phenotype, account for pregnancy loss) • Better clinical management (e.g. hormone treatment for Klinefelter syndrome) • Assess future reproductive risks (e.g. previous Down’s pregnancy, risk of live born abnormal child) • Prenatal diagnosis

What are the referral reasons for cytogenetic testing?

* prenatal diagnosis * birth defects * abnormal sexual development * infertility * recurrent fetal loss * leukaemias * solid tumours * prognostic information for specific translocations

What does balanced mutation mean?

* Person has chromosomal abnormality but the phenotype is balanced - no genetic information is lost and/or no phenotypic changes are apparent * DNA may be lost - eg p arms lost - but no phenotypic change

What does unbalanced mutation mean?

There is loss of genetic information and there are phenotypic changes apparent