Transcript Genetics Technology: Next Generation Sequencing in

Genetics Technology:
Next Generation Sequencing in
Clinical Practice
Dr Yvonne Wallis FRCPath
Principal Clinical Scientist
Head of Familial Cancer Services/
Head of Research, Academic and Service Developments
West Midlands Regional Genetics Laboratory
Healthcare Science Making an Impact in the New NHS
9th November 2012
Next Generation Sequencing:
a technology worth getting excited about
Landmarks in Genetics
Mendel
publishes
work on
inheritance
1866
Draft
sequence of
human
genome
Cost: $2.7 bn
Sanger
sequencing
first
reported
1953
The
structure of
DNA is
described
1977
Cost of
sequencing
a human
genome
reduced to
< $10,000
1983
Kary Mullis
invented
Polymerase
Chain
Reaction
2001
2005
Next
generation
sequencing
invented
2012
The importance of DNA sequencing
Sequencing decodes DNA to produce the precise order of
four component bases A, C, G and T
The order of these bases defines who and what we are now
and in the future
Changes to base sequence cause disease either inherited or
acquired during our lifetime
Next Generation Sequencing-a game changer
Capillary 2005
MiSeq
HiSeq
60,000 bases
150,000,000 bases
6,000,000,000 bases
0.002% of genome
2% of genome
2 whole genomes
10 genes
>20,000 genes
At WMRGL
Sequencing Facility
At WMRGL
Sequencing Facility
BGI@Bham
joint initiative
How is NGS improving patient care?
Massively Parallel Sequencing
Reduces cost
per base >1000x
Increases data
throughput per run
More genes More Patients
Increasing diagnostic yield
Reducing time to diagnosis
Challenges of NGS implementation
 Technology is demanding, relatively new & evolving
 Few standard protocols/Limited agreed best practise
 All new NGS workflows require significant validation
 Fit for purpose
 Best possible quality
 Specialist equipment and data storage requirements
 Trained workforce:
 Bioinformatics skills required for data analysis
 Clinical interpretation of base changes
Developed NGS service panels
Paraganglioma and
Phaeochromocytoma
9 genes
Renal Cell Carcinoma
5 genes
Colorectal Cancer
6 genes
Neonatal liver disease
6 genes
NGS service performance metrics
181 reports issued in 2012 using NGS technology
• Increasing number
reported every month
• Genetic cause confirmed
in 21 patients
Improved service for our users/patients
Phaeochromocytoma gene panel
Previous strategy
 5 genes analysed
 Cost = £1700
 Time = 10 months
NGS strategy
 9 genes analysed
 Cost = £500
 Time = 4 months
Case Study 1
Next
generation
sequencing
screen:
54 years
Mesenteric
paraganglioma
No F/H
3 children
Pathogenic
mutation
identified
RET
SDHB
SDHC
SDHD
VHL
DNA testing now
available to
appropriate
family members
MAX*
SDHA *
SDHF2*
TMEM127*
TMEM127*
c.268G>A p.Val90Met
Case Study 2
Next
generation
sequencing
screen
2 weeks
Neonatal
choleostasis
ABCB4
ABCB11
ATP8B1
NPC1
NPC2
SLC25A13
2 pathogenic
mutations
identified
NPC1
c.2000C>T
p.Ser667Phe
c.3182T>C
p.Ile1060Thr
Diagnosis of
Niemann Pick disease
Appropriate
treatment
Prenatal testing
available for
future
pregnancies
Diverse clinical applications of NGS
in development
Inherited
breast cancer
gene panel
11 genes
Diseases of
sexual
differentiation
panel
20 genes
Genomic
profiling in
acute myeloid
leukaemia
gene panel
Somatic
cancerstratified
medicine
gene panel
59 genes
60 genes
NGS-driven landmarks in Genomic Medicine
for Genetics Laboratories
Whole exome
sequencing:
Gene panel
screens:
Missing
heritability
Across all
areas of
medicine
Stratified
medicine
2012
2015-2020
Deep sequencing
for non- invasive
testing:
Prenatal diagnosis
Circulating tumour
markers
Whole genome
sequencing:
“One-stop shop”
Partnership for NGS-driven Genomic Medicine
Commercial
NHS
Academic
High Quality Patient Care
NGS: Changing Healthcare
Acknowledgements
• NGS Team
–
–
–
–
–
–
Eleanor Rattenberry
Kim Reay
Kirsten McKay
Lindsey Vialard
Anna Yeung
Hayley Bair
• Head of Cancer Programme
– Jennie Bell, FRCPath
• Director of WMRGL
– Professor Mike Griffiths