dna mutations Flashcards
mutation?
alternative dna sequence (variant)
polymorphism?
if variant occurs in over 0.01 freq of the population
rare mutation?
less than 0.01 of pop. It is pathological
mutation inherited if?
it is in germ line cells (gametes).
de novo?
new mutation in germ cells
what general ways do mutations usually occur?
copying error or environment
cancer?
mutation in somatic cells. uncontrolled cell division.
mutations can lead to 3 main outcomes? what are these?
1.loss of function 2.gain of function 3.dominant-neg effect.
explain loss of function
usually which inheritance and why?
mutation causes gene to become inactive. usually due to recessive disorder because in dom disorder still one working allele.
explain dominant negative effect
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.
types of mutation?
insertion (substitution) deletion, duplication, reaarrangements
missense mutation?
is replacing one amino acid with another. which can result in an abnormal or normal protein
nonsense?
results in a premature stop codon. results in usually a nonfunctional protein. mrna is unstable and it is degraded therefore no mutant protein.
point?
affects just 1 or few nucleotides.
splice site mutation?
which technique to analyse?
creates or destroys signals for intron splicing. defects confirmed by rt-pcr. it occurs during the processing of precursor mrna into mature rna.
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?
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
pseudogene?
is a inactive gene.
example of gene rearrangement?
gene inversion. end to end difference which disrupts order of exons.
example of gene inversion? (look over)
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.
example of disease caused by dominant negative mutation? (point mutation).
describe disease phenotype if nonsense mutation?
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.
how does a more severe version of Oi come about?
missense mutation. this causes misfolding of the protein. due to mutant chains. (complete loss is better)
why is there paternal age effect?
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.
example of paternal effect disease? and describe symptoms
achondroplasia (ach -weeman). stunted growth. short limbs. it is a bone growth defect.
molecular basis of ach? (point mutation)
increased dimer production. increased signalling molecules (fgf factor). reduced ossification. leads to less cartilage converted to bone.
Describe molecular basis and symptoms of Charcot-marie- tooth disease?
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.
How would you go about identifying a gene without any family information?
A disease this what done for?
Exome capture then sequence exome.
Kabuki syndrome.
