DNA

Question 1

what is penetrance?

Answer 1

likelihood of of having a disease if you have the mutation

100% penetrance means you definitely will get the disease

Question 2

what is a mendelian disorder?

Answer 2

disease which segregates in families predicted by mendel’s law

• basically a disease that is mainly caused by a change in a single gene
• high penetrance low prevelance

Question 3

3 possible outcomes of a genetic mutation?

Answer 3

causes a disease
causes a harmless polymorphism
mutation is of unknown significance

Question 4

events which occur in sequencing in an ideal scenario?

Answer 4

sequence entire genome/exome > keep variations that are in the right genes (genes associated with phenotype of disease) > keep variations that are expected to affect the gene (stops, frame shifts etc) > keep variations that are not listed as polymorphisms in the database

Question 5

how much of the genome is made of exons (parts actually codes for something)?

Answer 5

1-2%

called the exome

Question 6

in which 3 areas of the gene can a mutation occur and what are the effects of each?

Answer 6

intronic = in the intron (unlikely to cause effect)
mutation 1-2 bases into the intron (basically between intron and exon) = change to splice sequence, causes splicing error
exonic variant = within the exon (can cause change in amino acid sequence, create stop, frameshift or have no effect)

Question 7

how is a mutation described?

e.g SMAD4:p.Met157Thr ?

Answer 7

SMAD4 gene
the methionine at position 157 has been mutated to a threonine
(position 1 = first amino acid of the peptide sequence)

Question 8

SMAD4:p.Cys162Ter or SMAD4:P.Cys162 ?

Answer 8

the cystine at position 162 in SMAD4 gene has mutated to a stop codon

Question 9

SMAD4:c.471A>T?

Answer 9

the adenine at position 471 in the cDNA sequence has mutated to a thymine

Question 10

what can complicate next generation sequencing?

Answer 10

if there are lots of variations which arent listed as polymorphisms so need to figure out which is causing the disease

Question 11

what can help you figure out which variant is causing the disease?

Answer 11

look at phenotype of patient

Question 12

mendelian vs common disorders?

Answer 12

mendelian has higher penetrance and are less common

Question 13

what can cause familial young age MI?

Answer 13

familial hypercholesterolemia (total cholesterol >7.5 or LDL cholesterol >4.9)

Question 14

best test for multfactorial cardiovascular disease?

Answer 14

cholesterol