13. Intro To Mutations Flashcards
What are exogenous sources of mutation ?
ionising radiation
UV
Mutagenic chemicals
What are endogenous causes of mutation?
DNA replication errors
Endogenous free radical damage from metabolism
Transposable elements
What are transposable elements?
Specific DNA sequences >1 gene in length which move to random sites as a discrete unit.
How can transposable elements cause problems?
Insertion can inactivate the target gene
Insertion may disrupt promotor region
What are 3 types of single nucleotide mutations?
Deletion
Insertion
Substitution
Which single nucleotide changes will lead to a frameshift?
Deletions and insertions will alter the reading frame of the DNA downstream of the mutation.
What can be the effect of single nucleotide mutations?
Can change gene product
Can change the amount of gene product
Can change polypeptide length
Or may not have any effect at all
What is a transition mutation?
Change to the same type of base. E.g purine to purine
What is a translocation mutation?
Change to a different type of base. E.g purine to pyramidine
What mutation is involved in sickle cell anaemia?
A nucleotide substation in the 6th amino acid, causing glutamate to change to valine.
What is a mutation which alters the amino acid called?
missense
What are mutations which do not have an effect called?
Silent or neutral
What are mutations that change an amino acid to a stop codon called?
Nonsense - alter the length of the polypeptide
What mutations would alter the amount of gene product?
Mutations affecting transcription and translation - altering promotor activity, altering translation initiation at AUG or preventing mRNA splicing (sequence specific)
What types of chromosomal mutations can occur?
Deletions - lose gene(s)
Translocations - move to another chromosome
Inversions - after ds break
Insertions - transposable elements
Why is a deletion chromosomal mutation more detrimental than an inversion or translocation?
There is loss of genetic information, inversion and translocation there is no loss of genetic information
Define mutation.
A heritable alteration in a gene or chromosome
Or the process that produces the alteration.
Mutations vary depending on the source causing them. Describe possible changes that can occur.
Base dimerisation (thymine)
Double or single strand breaks
Mismatches of base pairs
Deamination
What can cause free radial production?
UV damage, smoking, ionising radiation, metabolism
How can transposable elements affect genes?
insertion into a gene will break the genetic code and inactivate the gene.
Transposing do not always have an effect. Why is this?
They may jump into a non-coding region of the gene.
Transposing can increase transcription of genes, how?
By inserting into the promotor region, can activate transcription
What are 2 sources of endogenous mutation?
Dna replication errors
Transposable elements
When is chromosome inversion most likely to occur?
After misrepair of a double stranded break
What is the difference between a chromosome substitution and a translocation?
A substitution is exchange of sections at any point in the chromosome, translocation is exchange of the ends of the chromosome.
What are symptoms of sickle cell anaemia?
Impaired growth,susceptibility to infections, weakness and tiredness
Which chain of haemoglobin is altered in sickle cell anaemia?
beta chain
What type of mutation occurs in sickle cell anaemia?
Missense - altered amino acid
Single nucleotide substitution
What type of mutations will change the length of the polypeptide?
Frameshift mutations
Mutations of stop codon
Nonsense mutations
When might a deletion or insertion not result in a frameshift?
If 3 bases or a multiple of 3 in the correct reading frame, will just remove or add those amino acids
