Week 2 - Bioinformatics - Tuesday 11th October

Question 1

Why do we need guidelines?

Answer 1

• Ensure guidelines are correct
• Ensure consistency of diagnosis
• Knowledge of the pathogenic variant can confirm diagnosis and help predict disease prognosis
• Variant specific treatments are becoming increasingly common

Question 2

What does ‘pathogenic’ mean?

Answer 2

Capability to cause disease.

Question 3

What does ‘benign’ mean?

Answer 3

No impact on health.

Question 4

What does ‘cosegregation’ mean?

Answer 4

• The likelihood of two units being inherited from one generation to the next or an interaction estimation probability between any number of loci
• The tendency for closely linked genes and genetic markers to be segregated (inherited) together

Question 5

What is the PVS1 interpretation criterion?

Answer 5

The 2015 ACMG/AMP sequence variant interpretation guideline provided a framework for classifying variants based on several benign and pathogenic evidence criteria, including a pathogenic criterion (PVS1) for predicted loss of function variants.

Question 6

What is the Grantham Score?

Answer 6

Prediction of the effect of substitutions between amino acids based on chemical properties, including polarity and molecular volume, characterised into classes of increasing chemical dissimilarity.