Genetics in sudden death Flashcards
define penetrance
likelihood of having a disease if you have the gene mutation
what does 100% penetrance mean
you will always get the disease if you have the mutation
Mendelian disorders have high/low penetrance
high
give examples of mendelian inheritance patterns
autosomal dominant
autosomal recessive
x-linked
Mendelian disorders are/not apparent in family history
are apparent in FH
why is next generation sequencing better than other techniques
can sequence multiple genes
cheaper
is a mutation always pathological
no, it can be
- disease causing mutation
- polymorphism
- variant of unknown significance
how can the clinical phenotype guide you
for certain phenotypes, you can then narrow down the genes to look for mutations
why cant you sequence all the genes in the body
because you might find something that you have not discussed with the patient
what is better, to examine the genome or the exome
exome - contains the DNA that actually codes for proteins
cheaper
there is a low/high likelihood of effect with a mutation in an intron
low
introns are non-coding
what causes a splicing error
change to splice sequence 1 or 2 bases into an intron
mutation in an exon has the potential to…
- change amino acid sequence
- stop mutation
- frameshift mutation
- no effect
how would you describe this mutation:
SMAD4:p.Met157Thr
SMAD4 = gene name
p. = peptide
the Methionine at 157 has mutated into Threonine
how would you describe this mutation:
SMAD4:p.Cys162Ter or
SMAD4:p.Cys162*
cystine at peptide sequence of SMAD4 at position 162 has mutated to a STOP codon
how would you describe this mutation:
SMAD4:c.471A>T
adenine at position 147 in cDNA has mutated into thymine
what is cDNA essentially the same as
mature mRNA with introns removed
why is phenotype important
tells you which genes are important
examples of genes implicated in a dissecting aortic aneurysm
TGFB1+2
Fibrillin
SMAD
how is Marfans syndrome inherited
AD - fibrillin mutation
characteristic features of Marfans
ectopia lentis - upward dislocation of lens
aortic aneurysm + dissection
valvular dysfunction
long fingers
what is Loeys Dietz syndrome
AD inheritance - TBR1/2 mutation
widely spaced eyes
tortuous vessels on angiogram
oddly shaped uvula
Mendelian disorders are rare/common
rare
what can a mutation in LDLR cause
familail hypercholesterolaemia
consequences of familial hypercholesterolaemia
MI at young age coronary artery disease tendon xanthomas xanthelasmas corneal arcus cholesterol >7.5
what is the most common cause of heart disease in the population
multifactorial
but a LDLR mutation would trump that
genetic testing is most useful for high/low penetrance disorders
high penetrance
mutations in difference genes can cause the same phenotype, true or false
what does this mean
true
means that these genes often cluster in related pathways
