Mutations Flashcards
Define mutation.
A change of nucleotide sequence.
What is mutagenesis?
The process of mutation generation.
What is deamination?
A mutation where C for example is turned into U.
Why might deamination not be a problem if C - G is turned into U - G?
Because during replication U - G might be replicated into C - G. This turns out to be completely fine because the that was the combination from the beginning.
However if U - G is replicated into U - A it might end up being replicated again into T - A. T - A is a completely different combination that can cause problem.
Give some exogenous sources of mutation.
Ionising radiation Environment Free radicals Mutagenic chemicals Anti-cancer agents
Give some endogenous sources of mutation.
DNA replication defects like deamination, mismatching etc.
Transposable elements.
What are transposable elements or also called transposons?
They used to be called jumping genes.
They are specific DNA sequences that can move to random sites on its DNA molecule.
Why can transposons cause a problem?
If they hop onto a part of the DNA sequence where it inactivates a gene or changes gene expression causing a mutation.
How does the size of a gene relate to the risk of transposons affecting them?
The bigger the gene the higher risk of a transposon hopping onto it and either activating it or inactivating it.
What are some positive outcomes of mutations?
It is a source of genome variation
It is a driving force of evolution
What is a SNP mutation?
Single nucleotide polymorphism when one single nucleotide is affected and altered/switched out or deleted/inserted.
Define anonymous SNP.
A SNP that doesn’t appear to have any effect.
Define non-coding SNP.
When SNP occurs outside a gene as it not coded for.
Define coding SNP.
When SNP occurs inside a gene and is coded for. This is the worst one.
On a micro scale (nucleotide scale) what is deletion, insertion and substitution?
Deletion is when a nucleotide is deleted so the sequence has one less nucleotide.
Insertion is when a nucleotide is inserted so the sequence has one more nucleotide.
Substitution is when one nucleotide is swapped into another nucleotide.
What are the mutations that can happen on a macro scale (chromosomal level)? Explain them briefly.
Deletion
Duplication
Inversion (a part of the chromosome is put upside-down)
Substitution (a part of the chromosome is put on another chromosome)
Translocation (two parts, one on each chromosome are swapped)
How is DNA read in transcription? How is mRNA synthesised?
Read 3’ to 5’
Made 5’ to 3’
How is mRNA read in translation? How is the polypeptide chain synthesised?
Read in 5’ to 3’
Made in N to C
Regarding SNP and substitution; what is transition?
When the base is changed to the same type. This means a purine goes to a purine (A G) or a pyrimidine goes to a pyrimidine (T C)
Regarding SNP and substitution; what is transversion?
When the base is changed to a different type. This means that a purine is changed to a pyrimidine or vice versa. (A T or C G)
What are some consequences of single nucleotide changes?
It can change the gene product (polypeptide or RNA)
It can change the amount made of the gene product
It can change the polypeptide length
It might not have an effect at all
Sickle cell anaemia is a mutation in the 7th codon of the HBB gene. Why is it said that the 6th amino acid is changed from glutamate to valine?
This is because codon 1 is the start codon methionine which is chopped off.
Sickle cell anaemia is a missense base substitution mutation where GAG goes to GTG. What would is the difference in the mRNA product?
GAG is supposed to make an mRNA that is GAG this means it’s read from CTC.
GTG instead makes GUG because what is read is the other strand which is no longer CTC but CAC instead.
What is a missense mutation?
A mutation which results in a codon that codes for a different amino acid. It is a type of non-synonymous mutation.
What is a silent or neutral mutation?
A mutation which doesn’t have an effect on the gene products.
What is a frameshift mutation?
When deletion or insertion has occurred an there is a shift either to the left or right. This means that codons will be completely different and all codons after the insertion or deletion may result in different gene products. This can also cause premature termination because a stop codon has been made or it might result in a longer polypeptide because a stop codon is gone.
What is a nonsense mutation?
A mutation which can be a substitution which either result in a premature stop codon or a stop codon being left out so translation continues. This changes the polypeptide length.
What alters the amount of gene product?
Mutations that occur in the regulatory sequences. Alters promoter activity Alters translation initiation at AUG Prevents mRNA splicing Reduces mRNA stability
What other type of mutations are there on a micro level?
An entire codon that is deleted or inserted (3 base pairs)
What is robertsonian translocation?
Look at page 42.
It’s when two different chromosomes break at their centromere. The acocentric parts are left alone and the two remaining parts fuse together. This results in 45 chromosomes instead of 46 because there are two acocentric parts that are not used.
What is polyploidy?
A gain of a haploid set of chromosomes resulting in 3n or 69 chromosomes.
This is usually caused by polyspermy.
What is aneuploidy?
A gain or loss of a chromosome. 45 or 47.
Why do trisomies and monosomies generally only occur in 21, 13, 18, X and Y?
They occur in other chromosomes as well, however those are usually not viable for life.
What is mosaicism caused by?
Non-disjunction in mitosis.
What is mosaicism?
The presence of two or more cell lines in an individual.
How can chromosomal abnormalities be tested?
By cytogenetic analysis (karyotyping e.g.)
Fluorescent in situ hybridisation (FISH)
Microarray hybridisation
DNA sequencing (and other molecular techniques)
Why would you do cytogenetic testing?
To form an accurate diagnosis and prognosis of clinical problems (account for miscarriage for example)
Better clinical management (hormone treatment in Klinefelter)
Assess future reproductive risks
Prenatal diagnosis
What is balanced reciprocal translocation?
When a part of the chromosome is swapped with another chromosome. However in a balanced case it is a small part with no phenotypic changes that are apparent.
What is reciprocal translocation?
When genetic material is swapped between usually two homologous chromosomes.
Why can reciprocal translocation be a problem?
When genetic material is changed on a chromosome.
Or when some of the matching sequences that are used when lining up and matching is done in meiosis have been swapped. That can cause 4 chromosomes to appear homologous and line up together. When they are pulled apart a numerous of consequences can occur.
What are the consequences of reciprocal translocation where non-homologous chromosomes line up as 4 together.
Because when they are pulled apart two of the normal might be pulled together resulting in a normal.
And the other two will be pulled together resulting in a balanced pair.
Unbalanced separation can also occur.
3:1 non disjunction can occur as well.
What are consequences of an individual with robertsonian translocation?
Usually there are no symptoms associated with robertsonian translocation.
However it has a high risk of resulting in aneuploidy of trisomy or monosomy.
Why are there usually no symptoms associated with robertsonian translocation?
Because the acrocentric parts of the chromosomes are lost. They are usually small and may only have a few genes on them. This means that they may not have much an effect.
