Whole Genome Sequencing - Week 5 Flashcards
PTF1A
recessive mutations in distal PTF1A enhancer cause isolated pancreatic agenesis
The vast majority of mutations currently known to cause monogenic disease are
protein coding mutations
Homozygosity mapping indicated a
shared region of homozygosity on chromosome 10 in three isolate pancreatic agensis families
Coding variants could not explain the
pancreatic agenesis in these families. Professor Weedon searched for non-coding disease causing mutations by integrating genome sequencing with epigenome maps from human pancreatic progenitor cells. The shared variant is located 25kb downstream of PTF1A in a putative enhancer. Sequencing the putative enhancer element in 18 probands with pancreatic agenesis identified 5 additional mutations in 8 patients. Transgenic reporter assays show that the element acts as an enhancer in mouse pancreatic progenitor cells and co-localises with PDX1. Chromatin conformation capture assays shows that the enhancer makes contact with the PTF1A promoter in human pancreatic progenitor cells.
100,000 genome project -
The DNA of a Nation
why is the 100,000 genome project important?
- Targeted disease prevention
- Early disease detection
- Accelerated diagnosis
- Targeted therapy
- Improves outcomes
- Monetarily
why is the 100,000 genome project important? Targeted disease prevention
Identification of predisposition markers of underlying processes can predict future disease
why is the 100,000 genome project important? Early disease detection
2-8 years before onset and symptoms become obvious with low coat stratification
why is the 100,000 genome project important? Accelerated diagnosis
based on underlying cause and incidental findings - rather than just grouped symptoms
why is the 100,000 genome project important? targeted therapy
identification of effective personalised treatments
why is the 100,000 genome project important? improves outcomes
Improves outcomes
why is the 100,000 genome project important?money
- greater efficiency from streamlined care pathways
- earlier and more precise diagnosis and treatment
- fewer and less complicated surgical interventions
- fewer patients getting cancer and other diseases
The genomic Treatment Cycle
Patient, clinical data, consent and sample collection, DNA extraction, Bio-repository, sequencing, variant calling, interpretation (GeCIPs), feedback to clinician, validation and treatment
The genomic treatment cycle GeCIPs -
interpretation
The genomic treatment cycle GMCs
validation, treatment, patient, clinical data, consents + sample collection, DNA extraction
