Molecular Genetics Flashcards
Polymorphism
any change to DNA sequence that is found in >1% of the time.
Mutation vs variant
Don’t really use mutation anymore. Variant - neutral. Doesn’t imply something wrong, just different.
Types of variants
Synonymous (same aa), non-synonymous (different aa), nonsense (stop codon inserted), read through (change so no stop codon, doesn’t stop)
Which types of variants are pathogenic for sure? Which are not?
Synonymous can be! If it makes a splice site it could be a problem. Non-syn: 3D change, functional domain, etc. Non-sense: usually, but if it’s close to end anyways, NBD. Read-through: depends how much is added.
PRSS1 test
Indirect detection. mutation in trypsinogen gene (prss1)- leads to pancreatitis. depends on penetrance and variable expressivity. not looking for exact change, just did it cleave or not (abnormal)
PCR
yeaaaaaaah. Direct detection. Used with BRCA1/2. Requires 17k bases.
Large deletion/insertion
Called CNV (copy number variation). Over 1kb in size. Look for using FISH, or microarray.
Trinucleotide repeats
Slippage of DNA poly. For Fragile X syndrome, 6-44 copies of CGG is stable. Over 200 is full mutation. Tested with southern blot (PCR is hard due to repeat).
Sensitivity vs specificity
True positive/(true pos + false neg) = sensitivity. True neg/(true neg + false pos) = specificity.
CF testing
Use IRT (immunoradioactive tyrosine) to screen then do DNA screen. Combo raises specificity and sensitivity.
Next generation sequencing
Cheaper, which one has the lawn with adaptors?….; cancer hot stop plate. Neat.
Non-invasive prenatal test
10% of the DNA in mother’s plasma is from the fetus - could use this to test for variants.
4 tests in the USA
Trisomies test. Done b/w 9-11 weeks. Price out of pocket in majority of cases, but not crazy expensive ($800-2500). Not perfect, so can’t terminate before another test.
Population genetics and factors
p^2 + 2pq + q^2. If the frequency work then it’s random in the population. Non-random due to founder effect, lethal conditions, assortative mating (ie deaf community), some benefit conferred (ie sickle cell anemia and malaria)
