DNA Analysis and Sudden Death

Question 1

What is meant by penetrance?

Answer 1

Likelihood of getting the disease if you have the mutation

=> 100% penetrance means you will always get the disease if you have the mutation

Question 2

What is meant by Mendelian disorders?

Answer 2

Disease caused by a single gene mutation

Rare in population but has High penetrance

Question 3

What is Next Generation Sequencing used for?

Answer 3

Analysis of multiple genes

• sequences small sections at a time
• lines these up to other gene copy to look for homo/heterozygous mutations

Question 4

What is central dogma used for?

Answer 4

• predicts what certain mutations will do to a gene

=> whether or not it will affect end result

Question 5

What could a change in the gene potentially be?

Answer 5

• disease causing mutation
• polymorphism
• variant of unknown significance

Question 6

How is data filtered in order to find the causative mutation?

Answer 6

• Sequence from exome
• Keep variations in right genes
• Keep variations expected to affect gene (stops, frame shifts etc.)
• Keep variations NOT listed as polymorphisms`

Question 7

What can cause a change in the splice junction of a gene?

Answer 7

mutation in the first few bases of an intron

Question 8

How would you describe this mutation:

SMAD4:p.Met157Thr

Answer 8

Methionine in position 157 of the peptide (p.) sequence of SMAD4 gene has mutated to Threonine

Question 9

What does “c.” in a mutation description mean?

Answer 9

part of cDNA strand

mature mRNA with introns removed before translation

Question 10

What causes of sudden death may have genetic components?

Answer 10

MI - familial hypercholesterolaemia

Aortic dissection - Marfans, Loeys Dietz

Question 11

Genetic causes of Aortic dissection usually have problems in the same signalling pathway. TRUE/FALSE?

Answer 11

TRUE

• e.g FIbrillin affected in MArfans
• TBR1 or TBR2 in Loeys Dietz

Question 12

How can patients with Loeys Dietz beb identified by their phenotype?

Answer 12

wide set eyes
carotid aneurysms
unusual uvula

Question 13

How many genes are known to cause Long QT and how many of these are common?

Answer 13

around 10 known

- 3 common

Question 14

A mutation causing problems with what receptor results in familial hypercholesterolaemia?

Answer 14

Low density lipoprotein receptor

Question 15

How do patients with familial hypercholesterolaemia usually present?

Answer 15

tendon xanthomas

corneal arcus