Mutation

Question 1

Give 3 examples of how DNA is damaged by chemicals

Answer 1

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

Question 2

How does UV light damage DNA?

Answer 2

Causes adjacent thymines to bond together to from thymine dimers- leads to single and so double strand breaks

Question 3

Give 3 examples of endogenous mutagens

Answer 3

Replication errors- Rna instead of dna, slippage, dna legions
Free radicals produces from metabolism
Transposable elements

Question 4

What is a transposable element?

Answer 4

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.

Question 5

What is the difference between transition and transversion single nucleotide changes?

Answer 5

Transition is between same types of bases (A-G or T-C-U)

Question 6

When is base excision repair used? What is the consequence of base excision repair going wrong?

Answer 6

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

Question 7

Out line the 3 responses to DNA damage detection

Answer 7

DNA repair- homologous/ non homologous end joining, base excision repair ect
Senescence- arrests cell cycle
Apoptosis- purposeful cell death

Question 8

What is a missense mutation?

Answer 8

A mutation that changes the amino acid coded for in the polypeptide

Question 9

What is a silent/ neutral/ synonymous mutation?

Answer 9

A mutation that does not result in a new amino acid being coded for

Question 10

What is a frame shift mutation?

Answer 10

Insertion or deletion or 1/2 nucleotides moving the reading frame meaning all amino acids downstream of the mutation are different

Question 11

What is a nonsense mutation?

Answer 11

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

Question 12

What/ where can there by a mutation that will change the amount of polypeptide being coded for?

Answer 12

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

Question 13

What types of chromosomal mutations are there?

Answer 13

Deletion, duplication, inversion, translocations, insertions

Question 14

What is the difference between aneuploidy and polyploidy?

Answer 14

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.

Question 15

What causes aneuploidy?

Answer 15

Non- disjunction (2 chromosomes go same way) or anaphase lag (one stays in the middle and is destroyed.)

Question 16

Describe the consequences of trisomy 21 (47 XX/XY +21)

Answer 16

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

Question 17

Describe name and consequences of trisomy 18

Answer 17

Edwards syndrome:
Small lower jaw
Large back of head
Overlapping fingers
Usually only live 5-15 days

Question 18

Describe name and consequences of trisomy 13

Answer 18

Patau syndrome:
Multiple congenital abnormalities
Polydactyly
Most die in prenatal period

Question 19

Describe name and consequences of X monosomy- why is only having one sex chromosome an issue?

Answer 19

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

Question 20

What is the name and consequences of having 47,XXY genotype?

Answer 20

Klinefelter syndrome- these individuals are usually fine as the 2nd x is inactivated. People with XXXY or XXXXY are at greater risk of symptoms

Question 21

What consequences if any are there to having extra Y chromosomes ?

Answer 21

none really but generally more ‘manly’- taller, more muscular, more aggressive and less intelligent.

Question 22

What is a reciprocal translocation?

Answer 22

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.

Question 23

What types of segregation leads to healthy and un healthy gametes after a reciprocal translocation?

Answer 23

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.

Question 24

What is a robertsonian translocation?

Answer 24

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.

Question 25

How is downs syndrome caused by a robertsonian translocation?

Answer 25

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.

Question 26

What is uniparental disomy and why is it as issue?

Answer 26

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.

Question 27

What conditions can be caused by uniparental disomy and what chromosomes involved?

Answer 27

Prayer willi/ Angethan syndrome (15)

Russel- silver/ beckwiedemann (11)

Question 28

Why may someone be offered a pre-natal test?

Answer 28

Serum markers suggest downs
Abnormalities in scans
Famillly history
DNA studies

Question 29

Give the 2 invasive methods of collecting DNA of prenatal testing and the adv of each

Answer 29

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

Question 30

How is non invasive prenatal testing done?

Answer 30

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