Looking To The Future

Question 1

Give two examples of disease mutation databases

Answer 1

• ClinVar

- DMuDB

Question 2

Give an example of a phenotype database

Answer 2

Human phenome project

Question 3

Give three examples of population variant databases

Answer 3

• dbSNP
• dbVar
• Universal Browser

Question 4

What are the four main functions of UCSC browser?

Answer 4

1. Visual exploration of genomic loci, genes or variants
2. Integration of visualised datasets (= tracks)
3. Interactive links over features to other databases
4. Upload or download datasets onto the UCSC viewer

Question 5

Name three different categories of NGS sequencing chemistry

Answer 5

• Semiconductor sequencing (e.g. Ion torrent)
• Sequencing by synthesis (e.g. Illumina, Roche)
• Single molecule real time (SMRT; e.g. Pacific biosciences)

Question 6

NGS mapping used what type of file

Answer 6

BAM file

Question 7

Give some example software tools for NGS variant calling

Answer 7

• GATK
• SAMtools
• Platypus

Question 8

What are channelopathies?

Answer 8

Diseases caused by disturbed function of ion channel subunits or the proteins that regulate them.

Question 9

Are channelopathies congenital or acquired?

Answer 9

They may be either:

• Congenital often result from one or more mutations in the encoding genes
• acquired often result from an autoimmune attack on an ion channel

Question 10

What are four main examples of channelopathies of human skeletal muscle?

Answer 10

• Hyperkalemic (high potassium) periodic paralysis
• Hypokalemic (low potassium) periodic paralysis
• Myotonia congenita
• Paramyotonia congenita

Question 11

What are the five types of ion channel that can be involved in epilepsy syndromes? What genes are implicated?

Answer 11

• Sodium (SCN1A etc)
• Potassium (KCNQ2 etc)
• Calcium (CACNA1A etc)
• Acetylcholine receptor (CHRNA4 etc)
• GABA (GABRD etc)

Question 12

Missense or nonsense mutations in SCN1A are present in over 80% of cases of what syndrome?

Answer 12

Severe myoclonic epilepsy of infancy (= Dravet syndrome)

Question 13

What is the underlying biology to channelopathies?

Answer 13

Ion channels are voltage gated. Ion channel mutations affect ionic charge and can either enhance channel activity (gain of function) or attenuate it (loss of function)