20.04.19 Whole genome sequencing projects e.g. 100,000 genomes

Question 1

What will 100,000 project sequence

Answer 1

• 25,000 cancer patients (blood and tumour)

- 17,000 people with rare diseases (plus 2 additional blood relatives)

Question 2

Who runs 100,000 project

Answer 2

Genomics health England. Part of Department of Health.

Question 3

Aims of 100,000 project

Answer 3

1. Create new genomic medicine service for NHS.
2. Enable new medical research.
   - Bring benefit to patients
   - Create ethical and transparent programme based on consent
   - Enable new scientific discovery and medical insights
   - Kick start the development of the UK genomics industry

Question 4

Key dates for 100,000 project

Answer 4

• Announced by PM in Dec 2012
• Genomics England launched 2013
• Project live 2015
• Deadline for labs to have 85% cases reported= April 2020.

Question 5

What is a GeCIP

Answer 5

• Genomics England Clinical Interpretation Partnership.

- Researchers from NHS and University involved in the analysis of sequence data.

Question 6

What is the approximate cost of 100,000 project

Answer 6

£206 million

Question 7

Where does sequencing take place for the 100,000 project

Answer 7

Hinxton. Provided by Illumina

Question 8

What is a GMC

Answer 8

• Genomic Medicine Centre
• 13
• Identify, enroll and register suitable patients. Obtain consent and detailed phenotypic information. Validate findings.

Question 9

What information is fed back to patients (100,000 project)

Answer 9

• Pertinent findings regarding their main condition.
• Patients can opt for feedback on high probability pathogenic findings (will develop as project progresses)
• Information on 12 serious actionable conditions, e.g. cancer predisposition (BRCA, FAP)
• Carrier status (CF, sickle cell, DMD, SMA type 1)

Question 10

WGS as part of NHS genomic medicine service in future

Answer 10

• January 2020, Genomics England announced that 300,000 genomes would be delivered over the next 5 years.
• Done through 7 Genomic Laboratory Hubs (GLH).
• Certain cancers and rare diseases will be eligible
• Aim to support diagnosis, inform and improve treatment pathways and thus outcomes.
• Due to go live in 2020

Question 11

What is the Scottish Genome Partnership (SGP)

Answer 11

• £15 million investment by University of Edinburgh and Glasgow in Jan 2015.
• Sequencing of 3,000 Scottish genomes.
• Started March 2016.

Question 12

What is the ENCODE project

Answer 12

• ENCODE= Encyclopedia of DNA elements
• Public research consortium launched by US National Human Genome Research Institute (NHGRI) in 2003.
• Aims to build a comprehensive catalog of candidate functional elements in the human genome.
• Includes data sets from ChIP-seq, RNAseq, DNA methylation etc

Question 13

What is the BiLEVE project

Answer 13

• UK Biobank Lung Exome Variant Evaluation
• One of the first studies using samples and data from UK biobank (resource from 500k volunteers).
• Study into the genetics of lung disease, particularly chronic obstructive pulmonary disease.
• Associations between SNPs and lung function, chance of developing disease in smokers vs non-smokers. Smoking addiction.
• Genome wide genotyping using Affymetrix array

Question 14

What is the PAGE study (not prenatal genome project)

Answer 14

• PAGE= Population Architecture using Genomics and Epidemiology
• US study initiated in 2008 by NHGRI.
• Investigates the epidemiologic architecture of well-replicated genetic variants associated with complex disease in large, ethnically diverse population-based studies.
• 270,000 participants.

Question 15

What is the DDD study

Answer 15

• DDD= Deciphering Developmental Delay
• Funded by Wellcome Trust, Department of Health and NIHR
• Patients with severe undiagnosed developmental disorders and their parents using a combination of exome sequencing and array-based detection of chromosomal re-arrangements.
• 14k families recruited.
• Diagnostic yield is 35%
• 10% trios have an affected parent.
• 12 new genes identified

Question 16

Future investigations of DDD project

Answer 16

• Families with no diagnosis, WGS via 100,000 project.
• Transcriptomes, epigenomes, metabolomes.
• Meta-analyses with other datasets to increase sample sizes.
• Polygenic causes

Question 17

What is the BRIDGE consortium

Answer 17

• NIHR Bioresource funded NGS projects
• Aim to discover sequence variants underlying rare diseases.
• Evaluate the sensitivity and specificity of exome or other NGS approaches to identify known high penetrant disease causing variants.