GEN: Investigating the Genome

Question 1

what are the benefits in sequencing a whole genome instead of just exons?

Answer 1

• cost is lower: £1000
• reveals more - full range of possible data
• complete
• whole genome does not change in lifetime
• only need to analyse each time for a specific question
• potential to collect once, store and refer to for care

Question 2

what is next generation sequencing NGS?

Answer 2

• new technology - reason why whole genome sequencing is so cheap
• based on sequencing billions of random fragments in parallel

Question 3

what are variants only in one copy called?

Answer 3

HET variant

Question 4

what are the limitations to the current technology?

Answer 4

Short reads of NGS make accurate characterisation of
large variants hard

NGS accuracy lower than older sequencing technology

Question 5

how are causal variants identified?

Answer 5

• filter variants frequently observed (remove non-rare)
• look for variants identified as pathogenic
• look for variants in genes linked to condition
• look for variants effecting functional elements (splicing, protein coding sequence, regulatory element)
• look for variants that are normally conserved

Question 6

why is use of whole genome sequencing currently restricted and the recommendations of the 100 genome projects being rare diseases?

Answer 6

• limit applications to:
  • monogenic diseases (single variant)
  • patients with a clear phenotype so can focus on genes known to be associated with condition
  • patients who are ill

Therefore cannot currently be usefully applied to:
– Diagnosis of complex diseases: e.g. diabetes
– Prediction of risk: e.g. patients worried about
23andme result
– Patients with unexplained condition

Question 7

what was the 100,000 genomes original project?

Answer 7

NHS transformation project sequencing rare diseases and cancer

Question 8

who are the genome interpretation providers?

Answer 8

micia, congenica and wixinextcods