dna mutations

Question 1

mutation?

Answer 1

alternative dna sequence (variant)

Question 2

polymorphism?

Answer 2

if variant occurs in over 0.01 freq of the population

Question 3

rare mutation?

Answer 3

less than 0.01 of pop. It is pathological

Question 4

mutation inherited if?

Answer 4

it is in germ line cells (gametes).

Question 5

de novo?

Answer 5

new mutation in germ cells

Question 6

what general ways do mutations usually occur?

Answer 6

copying error or environment

Question 7

cancer?

Answer 7

mutation in somatic cells. uncontrolled cell division.

Question 8

mutations can lead to 3 main outcomes? what are these?

Answer 8

1.loss of function 2.gain of function 3.dominant-neg effect.

Question 9

explain loss of function

usually which inheritance and why?

Answer 9

mutation causes gene to become inactive. usually due to recessive disorder because in dom disorder still one working allele.

Question 10

explain dominant negative effect

Answer 10

product of one allele interferes with the the product of the other allele. this is usually because proteins are dimers (complexes) so therefore changes overall protein conformation. this means heteros have severe phenotype.

Question 11

types of mutation?

Answer 11

insertion (substitution) deletion, duplication, reaarrangements

Question 12

missense mutation?

Answer 12

is replacing one amino acid with another. which can result in an abnormal or normal protein

Question 13

nonsense?

Answer 13

results in a premature stop codon. results in usually a nonfunctional protein. mrna is unstable and it is degraded therefore no mutant protein.

Question 14

point?

Answer 14

affects just 1 or few nucleotides.

Question 15

splice site mutation?

which technique to analyse?

Answer 15

creates or destroys signals for intron splicing. defects confirmed by rt-pcr. it occurs during the processing of precursor mrna into mature rna.

Question 16

how does a chrom result in just 1 or 3 functional genes?
what condition is an e.g. of this? (deletion)
what are the properties of this disease?

Answer 16

this can be due to chromosome misalignment in meiosis and then a unequal crossover event.
unequal crossing over often removes the a-globin gene leading to alpha- thalassemia.
Sickle cell

Question 17

pseudogene?

Answer 17

is a inactive gene.

Question 18

example of gene rearrangement?

Answer 18

gene inversion. end to end difference which disrupts order of exons.

Question 19

example of gene inversion? (look over)

Answer 19

haemophila A. mutation in factor 8 gene that encodes factor viii needed in blood clotting. inverted repeats mispair causing a loop and the inversion of intervening dna.

Question 20

example of disease caused by dominant negative mutation? (point mutation).
describe disease phenotype if nonsense mutation?

Answer 20

brittle bone disease. osteogenesis imperfecta (OI).
it is a collagen mutation. made up of 3 aa chains encoded by 2 genes. if nonsense mutation in one allele of one gene than 1/2 as much protein.

Question 21

how does a more severe version of Oi come about?

Answer 21

missense mutation. this causes misfolding of the protein. due to mutant chains. (complete loss is better)

Question 22

why is there paternal age effect?

Answer 22

the risk of genetic disorders increases with dads age due to sperm having to go through many replications.
Also the sperm progenitor have a growth advantage.

Question 23

example of paternal effect disease? and describe symptoms

Answer 23

achondroplasia (ach -weeman). stunted growth. short limbs. it is a bone growth defect.

Question 24

molecular basis of ach? (point mutation)

Answer 24

increased dimer production. increased signalling molecules (fgf factor). reduced ossification. leads to less cartilage converted to bone.

Question 25

Describe molecular basis and symptoms of Charcot-marie- tooth disease?

Answer 25

Duplication of the PMP22 gene (usually). 3 genes instead of 2. The repeated sequences either side of the gene makes mispairing more likely.
Neurological disease- abnormalities in myelination.

Question 26

How would you go about identifying a gene without any family information?
A disease this what done for?

Answer 26

Exome capture then sequence exome.

Kabuki syndrome.