Genetics Flashcards
what genes do you analyse in next gen sequencing
only phenotypically relevant ones filter out: -variations in non relevant genes -variations unlikely to affect the gene (keep stops, frame shifts etc) -polymorphisms
what is penetrance
the likelihood of having a disease if you have a gene mutation
what are mendelian disorders
diseases the segregate in families in the manner predicted by mendels laws
(essentially a disease that is caused by a change in a single gene- high penetrance)
how much on genome codes
1-2% (sequencing exome only cheaper)
what causes a change to splice site
a mutation usually 1 or 2 bases into intron causing splicing error
what do exonic variants have the potential to cause
change in amino acid sequence
create stop
cause frame shift
have no effect
what is an intronic variant likely to cause
nothing
how do you name mutations
Position 1 is the first amino acid of the peptide sequence
stop is a *
e.g. A>T adenine mutated to thymine
what is cDNA
the mature mRNA sequence with the introns removed, referenced to the first base of the first codon
what would make you suspicious of a genetic dissecting aortic aneurysm
FHx
characteristic features of e.g. marfans
what genes cause marfans
fibrillin genes:
SMAD
Tbeta
when is genetic testing worthwhilw in thoracic aortic aneurysms
if familial or syndromic
what are features of loeys dietz syndrome
tortuous blood vessels
widely spaced eyes
abnormal uvula
TBR1/2 mutation
what causes genetic hypercholesterolaemia
LDL (low density lipoprotein) receptor mutation- LDL not internalised by liver to be metabolised
what are the features of familial hypercholesterolaemia
hypercholesterolaemia tendon xanthomas DNA mutation in LDLR, APOB or PCSK9 FHx of premature myocardial infarction (<50 in 2nd degree rel, <60 in 1st) or hypercholesterolaemia corneus archus
why is a deletion in an exon likely to be pathogenic
as will cause frameshift
in pedigrees are men square or round
men square
women round
for a disease that is AD inheritance, why might only 1 family member be affected
variable penetrance
other family members may be asymptomatic/ not diagnosed yet
novel mutation
what tests for long QT syndrome
ECG- as highly variable, need to do repeated ones
stress/ exercise ECGs
ambulatory ECGs
genetic testing
what is the management for long QT syndrome
beta blockers
ICD
avoid clarirthromycin and other QT prolonging drugs
who is shaded in a family tree
those affected by the gene/ disease
what is the most common mode of inheritance for heart disease
multifactoral
what is the chance of being affected by an autosomal dominant condition if parent affected
50%
what is the best test for familial hypercholesterolaemia
cholesterol blood test
should you treat children with family hypercholesterolaemia with statins
yes from the age of 10
what are the SEs of statins
muscle pain and weakness
nausea, diarrhoea, GI discomfort
what is a new treatment for hypercholesterolaemia
anti PCSK9 therapy
what bioinformatic information can help decide the importance of a variant
allele frequency
importance of the gene its in
comparison to other animals and humans
what the best test to determine risk of HCM
echo
if they have HCM can then look for genetic cause
what is brugada syndrome
intermittent disorder of cardiac depolarisation causing arrhythmia
ecg- ST elevation, broad QRS
patient will be young, look grey and have sense of impending doom
what can be given to diagnose brugada syndrome
give flecanide and do ECG- will stimulate arrhythmia
why do you get broad QRSs in VT
as conduction not through bundle of his so slower
what is the immediate Tx for VT
cardioversion
what is the treatment for torsades de pointes in LQTS
cardiovert
beta blockers
ICD
correct electrolyte abnormalities (hypokalaemia/ magnesaemia/ calcaemia) avoid swimming - dangerous environment beta blockers ICD (high morbility) loud noises - alarm clock in morning
hard to manage
?anti-arrhythmic drugs : quinidine, flecainide
ICD hard with children as increased body use, pyschological issues and inappropriate discharges due to T wave oversensing
why are MIs more likely when its cold
vasoconstriction
