Mutation Flashcards
Give 3 examples of how DNA is damaged by chemicals
Nitrous acid- deaminates bases, changes cytosine to uracil and adenosine to hypoxyanamthine (pairs w/ cytosine)
Tautomeric shifts: small changes in the molecules which causes changes in the H bonding properties so bases bond with non- complimentary bases
Base analogs: eg 5-bromouracil is similar to thymine so can be inserted in thymines place but it bonds with guanine not adenosine
How does UV light damage DNA?
Causes adjacent thymines to bond together to from thymine dimers- leads to single and so double strand breaks
Give 3 examples of endogenous mutagens
Replication errors- Rna instead of dna, slippage, dna legions
Free radicals produces from metabolism
Transposable elements
What is a transposable element?
Sequences of DNA which move to random sites in the DN sequence. They could insert in a gene, intron, promoter sequence ect, causing various effects.
What is the difference between transition and transversion single nucleotide changes?
Transition is between same types of bases (A-G or T-C-U)
When is base excision repair used? What is the consequence of base excision repair going wrong?
It is used when polymerase put in the wrong base(s). Errpors in BER can lead to SSB and this can lead to DSS. This is how the BRCA1 gene defect causes breast cancer
Out line the 3 responses to DNA damage detection
DNA repair- homologous/ non homologous end joining, base excision repair ect
Senescence- arrests cell cycle
Apoptosis- purposeful cell death
What is a missense mutation?
A mutation that changes the amino acid coded for in the polypeptide
What is a silent/ neutral/ synonymous mutation?
A mutation that does not result in a new amino acid being coded for
What is a frame shift mutation?
Insertion or deletion or 1/2 nucleotides moving the reading frame meaning all amino acids downstream of the mutation are different
What is a nonsense mutation?
A triplet coding for a normal amino acid is mutated to code for a stop codon (UAA, UAG or UGA) and so the polypeptide is cut shorter
What/ where can there by a mutation that will change the amount of polypeptide being coded for?
Can mutate the promoter/ enhancer sequence, can alter cleavage site of poly A polymerase, can prevent splicing, can change initiation sequence so it cannot start
What types of chromosomal mutations are there?
Deletion, duplication, inversion, translocations, insertions
What is the difference between aneuploidy and polyploidy?
Aneuploidy is loss or gain of chromosomes- called trisomy or monosomy.
Polyploidy is changes in the number of chromosome sets, usually due to fertilisation by > 1 sperm. Called triploidy or tetraploidy.
What causes aneuploidy?
Non- disjunction (2 chromosomes go same way) or anaphase lag (one stays in the middle and is destroyed.)
Describe the consequences of trisomy 21 (47 XX/XY +21)
Downs syndrome- Low muscle tone in babies (hypertonia) Furrowed tongues Skin folds in corner or eye lids Heart defects Early Alzheimer's High prevalence of leukaemia
Describe name and consequences of trisomy 18
Edwards syndrome: Small lower jaw Large back of head Overlapping fingers Usually only live 5-15 days
Describe name and consequences of trisomy 13
Patau syndrome:
Multiple congenital abnormalities
Polydactyly
Most die in prenatal period
Describe name and consequences of X monosomy- why is only having one sex chromosome an issue?
Turners syndrome: Some genes in common areas of the sex chromosomes (PAR1 and PAR2) need to be present twice. Causes short stature (only 1 SHOX gene) Heart defects Infertility- rudimentary ovaries Puffiness of hands and feet
What is the name and consequences of having 47,XXY genotype?
Klinefelter syndrome- these individuals are usually fine as the 2nd x is inactivated. People with XXXY or XXXXY are at greater risk of symptoms
What consequences if any are there to having extra Y chromosomes ?
none really but generally more ‘manly’- taller, more muscular, more aggressive and less intelligent.
What is a reciprocal translocation?
Where one part of a chromosome breaks off and swaps with another part.
They are generally healthy because all the genetic info is still there.
What types of segregation leads to healthy and un healthy gametes after a reciprocal translocation?
In alternative segregation the gametes are all healthy. One cell gets both normal chromosomes and the other gets both translocated chromosomes, they therefor have all the genetic info (balanced)
In adjacent segregation the gametes produced are unbalanced, this is because each cell gets one normal and one translocated chromosome, so some info is there twice and some is missing.
In the second adjacent segregation homologous centromeres go the same way, this is rare as is basically like non-disjunction of both translocated chromosomes.
You can also get 3:1 nondisjunction where one cell gets both homologous chromosomes and one of the other and the other only gets one chromosome from one of the pairs.
What is a robertsonian translocation?
Where the long arms (q) of two acrocentric chromosomes fuse to create one very long chromosome and one made of the two short arms (p)- this chromosome is usually degraded and lost.
How is downs syndrome caused by a robertsonian translocation?
There is a robertsonian translocation of the two chromosome 21 in one parent. The super chromosome produced (made up word) contains most of the info on chromosome 21 twice. This is passed onto two of the 4 gametes. If this gamete is fertilised the offspring will have this and the other parents normal 21. They will therefor only have 46 chromosomes but effectively have 3x chromosome 21s.
What is uniparental disomy and why is it as issue?
When you get two homologous chromosomes from one parent.
It is an issue because some genes are only expressed depending on parental origin of the chromosome. Therefor if it is missing or extra is will be over/ under expressed. This is called imprinting.
What conditions can be caused by uniparental disomy and what chromosomes involved?
Prayer willi/ Angethan syndrome (15)
Russel- silver/ beckwiedemann (11)
Why may someone be offered a pre-natal test?
Serum markers suggest downs
Abnormalities in scans
Famillly history
DNA studies
Give the 2 invasive methods of collecting DNA of prenatal testing and the adv of each
Aminocentesis- taking amniotic fluid sample can be used done from 15 weeks and 0.8% risk of miscarriage
Chorionic villus- Collect part of foetal tissue that forms placenta. Higher risk of miscarriage but can be done after only 2 weeks
How is non invasive prenatal testing done?
Take blood sample from mum and 5% of free floating DNA will be the foetus’. Can screen for diseases such as downs but an invasive test will be needed to confirm and cannot analyse chromosomes (as not in cells) and the DNA degrades quickly
