Investigating the genome Flashcards
Benefits of whole genome sequencing
whole genome is complete, individual’s genome doesn’t change, potential to collect once and store to analyse for specific question
What types of variations are there
SNV, deletion, insertion, inversion, translocation
What are the limitations of New Genome sequencing
short reads of NGS make accurate characterisation of large variants hard
NGS accuracy lower than older more expensie sequencing technology
what is the difference between the whole exome and the whole genome
whole exome: 30-50 million bases with around 20,000 variants
whole genome: 3 billion bases, 3 million variants
what strategies are used to identify causal variants
filter variants that are frequently observed, look for variants identified as pathogenic, look for variants in genes linked to condition, look for variants that effect functional elements (protein coding sequence, splicing, regulatory elements), look for variants that are normally conserved
Why do pathogenic variants give false positives
On the database, some variants documented as being causal but are common variants in reality. Frequency of variant occurrence has only recently been surveyed.
What are sources of information about variants
functional annotation of the reference genome
occurrence between affected and unaffected individuals
What do you do differently in clinical diagnostics and research
research-sequences of groups of affected individuals, looking to identify genes sharing variants
diagnostics-sequences of affected individual+other family members
WGS what is its applicaation and reporting limited to
Application: monogenic diseases, patients with a clear phenotype, patients who are ill
Reporting-variants in protein coding sequences (easier to predict effect of mutation
What can WGS not be applied to
diagnosis of complex diseases, prediction of risk, patients with unexplained condition
What was the objective of 100,000 genome project
treatment project, all whole genome sequencing for rare diseasess+cancer
improve health, stimulate wealth generationl create legacy of infrastructure, human capacity and capability,enable large scale genomics
What information is fed back to the NHS
patient’s main condition, additional serious and actionable conditions (optional), carrier status for non affected parents of children with rare diseases (optional))
