The Omni2.5

GWAS Seminar Series
NIH
Bethesda, MD
September 29, 2010
© 2010 Illumina, Inc. All rights reserved.
Illumina, illuminaDx, Solexa, Making Sense Out of Life, Oligator, Sentrix, GoldenGate, GoldenGate Indexing, DASL, BeadArray, Array of Arrays, Infinium, BeadXpress, VeraCode, IntelliHyb,
iSelect, CSPro, and GenomeStudio are registered trademarks or trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective owners.
Agenda
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Illumina is partnering with the scientific community to develop new and creative visualization
and data analysis techniques.
Illumina’s technologies are providing the foundation for understanding disease at the
molecular level, leading to radical improvements in human health over the next decade.
Achieving this vision will require empowering and accelerating the analysis, visualization,
and interpretation of data being generated with these innovative technologies.
Academic Awards: Overall Winner, Most Creative Algorithm, and Most Creative Visualization.
Commercial Awards: Overall Winner, Most Creative Algorithm, and Most Creative
Visualization.
Award: $50,000 USD Grant
Award: 1 yr Illumina co-marketing package
© 2010 Illumina, Inc. All rights reserved.
Illumina, illuminaDx, Solexa, Making Sense Out of Life, Oligator, Sentrix, GoldenGate, GoldenGate Indexing, DASL, BeadArray, Array of Arrays, Infinium, BeadXpress, VeraCode, IntelliHyb,
iSelect, CSPro, and GenomeStudio are registered trademarks or trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective owners.
Register today.
www.illumina.com/iDEA
Judged by a panel of independent experts Submissions Due: March 15, 2011 Awards Announced June,
Timeline:
Launched June 2010
Entry submission due by 5pm PST March 15, 2011
Awards presented at iDEA Conference in June 2011 in San Diego
Judging:
Judged by a set of independent (non-illumina) experts in the field including:
Steven Jones, Jared Maguire, John Quackenbush, Steven Salzberg
More information on judging criteria is available on the iDEA website
All awards will be presented at the iDEA Conference June 2011 in San Diego
Other:
We are providing a dataset with illumina data types (entries are not required to use the iDEA
dataset)
Entries do not need to include functioning software
Illumina is not expecting any IP from entries.
How to register / find more information: www.illumina.com/iDEA
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Illumina’s GWAS
Roadmap:
next-generation
genotyping studies in
the post-1KGP era
Jennifer L. Stone, PhD
Product Manager
Genotyping Applications
© 2010 Illumina, Inc. All rights reserved.
Illumina, illuminaDx, Solexa, Making Sense Out of Life, Oligator, Sentrix, GoldenGate, GoldenGate Indexing, DASL, BeadArray, Array of Arrays, Infinium, BeadXpress, VeraCode, IntelliHyb,
iSelect, CSPro, and GenomeStudio are registered trademarks or trademarks of Illumina, Inc. All other brands and names contained herein are the property of their respective owners.
Overview
First-gen GWAS vs. Next-gen GWAS
Next-gen Sequencing and the 1kGP Revolution
Illumina’s GWAS Roadmap
6
First-gen GWAS vs. Next-gen GWAS
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The GWAS approach is successful in human
genetics
Year
8
# of
publications
2005
2
2006
8
2007
89
2008
151
2009
222
First publications in 2005
Almost 600 total publications since
Over 3500 associations published
Wide-range of phenotypes and
diseases
Published Genome-Wide Associations through 9/2009,
536 published GWA at p < 5 x 10-8
NHGRI GWA Catalog
www.genome.gov/GWAStudies
9
The Case of the Missing Heritability
For most common diseases, the sum of individual effects found so far
is much less than the total estimated heritability
100%
Rare
Common Disease/Traits
80%
60%
Missing
40%
Explained
20%
0%
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Heritability
Adapted from Manolio et al 2009
Tackling the Full Spectrum of Variants in Disease
Large
NEW!
SEQUENCING
LINKAGE
(Common Variants
Large Effect Size)
Very Rare Variants
Large Effect Size
Effect size
NEW!
Next-gen GWAS
Rare/Intermediate Variants
Intermediate Effect Size
NEW!
Small
Next-gen GWAS
GWAS
(Rare Variants
Minimal Effect Size)
Common Variants
Small Effect Size
Low
High
Allele Frequency
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Enabling discoveries with the right technology
SEQ or
ARRAYS
Next-Gen
Arrays
1st Gen Arrays
Very Rare Variants
Large Effect Size
Effect Size
Large
SEQ
Rare/Intermediate Variants
Intermediate Effect Size
Small
Common Variants
Small Effect Size
Rare
Common
MAF
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Next-gen Sequencing and the 1kGP
Revolution
a new era beyond the HapMap Project
13
ARRAYS
Targeted
resequencing
Next-Gen Sequencing
Next-gen GWAS
Arrays
High Density Custom Arrays
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The 1,000 Genomes Project
Sequence 2,500 genomes to complete the picture of genetic variation
Achieve a nearly complete catalog of common human genetic
variants with frequency 1% or higher.
Project Goals
Accelerate fine-mapping efforts in gene regions
indentified through genome-wide association studies
or candidate gene studies
1.
2.
Improve the power of future genetic association
studies by enabling design of next-generation
genotyping microarrays that more fully represent
human genetic variation
3.
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Enhance the analysis of ongoing and already
completed association studies by improving our
ability to “impute” or “predict” untyped genetic
variants
New Content for Next-gen GWAS Arrays
Rich content to explore new hypotheses and enable new discoveries
Sequence to discover SNPs >1% MAF (1000-Genomes project)
Leverage the power of LD to select tagSNPs and remove redundancy
Include progressively more SNPs at lower allele frequencies (5%, 2.5%, 1%)
Tag SNPs
needed for Lower limit of
max
allele frequency
% variation
coverage
targeted
tagged (r2>0.8)
Project
Year
Approx.
Cumulative
SNPs found
HapMap
2003-2007
3M
~0.6M
5%
>90%
1kG Pilot Project
2008-2009
13M
~2.5M
2.5%
~80%
1kG Full Project
2010
35M*
~5.0M
1%
>90%
* Estimated
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HapMap Represents a Small Part of All Variation
SNPs by observations in 60 CEU Samples
1.0
HapMap
1000 Genomes
Count (x 106)
0.8
0.6
0.4
0.2
0.0
0
10
20
30
40
50
Minor Alleles
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60
Illumina’s GWAS Roadmap
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GWAS Roadmap Review
Content Source
HapMap Phase 1
HapMap Phase 2
HapMap Phase 3
1,000 Genomes Project
Array Products
HumanOmni1-Quad & OmniExpress
5M
Human1M-Duo
Human660-Quad
HumanHap500
HumanHap300
2.5M
1M
550K
317K
660K
Current
Projected
Announcement at ASHG, Oct 2009
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Data Points per Sample
Future GWAS Products
The Omni Family of Microarrays
Next-generation GWAS. NOW.
Omni
Express*
Omni1Quad
Highestthroughput array
with industryproven quality at
an exceptional
price.
Optimal
combination of
common SNPs,
CNVs, and
content from
1kGP.
MAF > 5%
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Omni1S-8
Takes researchers
from
Omni1/Express to
2.5M
Omni2.5Quad
Omni2.5S
Omni5
The most
The ultimate
optimal and
GWAS tool
comprehensive
~2.5M additional
providing near
set of both
markers providing
complete
common and
rare 1kGP content
coverage of
rare SNP
common and rare
content from the
variation
1kGP
MAF >2.5%
MAF > 1%
Illumina’s GWAS Roadmap
Content optimized from next-gen
re-sequencing efforts such as
1000 Genomes.
Pushing the boundary of GWAS
content into unexplored territory
Cost effective path for researchers
that want to ride the cutting edge
today
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Roadmap Paths
Path
Step 1 
Step 2

Step 3
1
~4.4 Million
OmniExpress
Omni1S
Omni2.5S
2
~5 Million
Omni1
Omni1S
3
Omni2.5S
~5 Million
Omni2.5
4
Omni2.5S
~5 Million
Omni5
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Total Markers
2010 GWAS Roadmap
Multiple chips made Easier with the Multi-use Workflow
Roadmap Entry Point
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Second Array
Third Array
Omni1-Quad
Multi-use
Omni1S
Multi-use
Omni2.5S
Multi-use
OmniExpress
Multi-use
Omni1S
Multi-use
Omni2.5S
Multi-use
Omni2.5
Multi-use
Omni2.5S
Multi-use
Omni2.5 Details
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HapMap represents only a small part of the common
variation
SNPs by observations in 60 CEU samples
1.0
HapMap
1000 Genomes
Count (x 106)
0.8
0.6
0.4
0.2
0.0
0
10
20
30
40
50
Minor Alleles
25
60
This is not just an array with “new” content!
The Omni2.5 array is a complete game-changer!
CEU Coverage Estimates: HapMap vs. 1kGP Reference Data
100%
90%
% Captured at r2>0.8
80%
70%
60%
50%
40%
30%
20%
10%
0%
Competitor
“New Array”
*
HapMap 5%
26
*Base content only
Competitor
“Old 900K”
660W
1kGP 5%
Omni1/
OmniExpress
1kGP 2.5%
Omni2.5
Genomic Coverage Stats for African Populations
YRI Coverage Estimates: HapMap vs. 1kGP Pilot Data
1
0.9
0.8
% Captured at r2 >0.8
0.7
0.6
HapMap 5%
0.5
1kGP 5%
1kGP 2.5%
0.4
0.3
0.2
0.1
0
Competitor
"New Array" *
27
*Base content only
Competitor
"Old 900K"
660W
Omni1/ OmniExpress
Omni2.5
Genomic Coverage Stats for Asian Populations
CHB/JPT Coverage Estimates: HapMap vs. 1kGP Pilot Data
1
0.9
0.8
% Captured at r2 >0.8
0.7
0.6
HapMap 5%
0.5
1kGP 5%
1kGP 2.5%
0.4
0.3
0.2
0.1
0
Competitor
"New Array" *
28
*Base content only
Competitor
"Old 900K"
660W
Omni1/ OmniExpress
Omni2.5
Enabling discoveries with next-gen GWAS
Arrays
6.0
3.0
1.5
1.1
Very Rare Variants
Large Effect Size
Sequencing
Effect size
12.0
(Common Variants
Large Effect Size)
Omni5M
Omni2.5M
Omni1
Rare/Intermediate Variants
Intermediate Effect Size
(Rare Variants
Minimal Effect Size)
1%
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Common Variants
Small Effect Size
5%
Allele Frequency
25%
Summary
First-generation GWAS has provided a foundation for beginning to
understand the genetic architecture of many diseases and traits.
However, first-generation GWAS was limited by the extent of knowledge
about the spectrum of variation in humans in the HapMap era.
NGS re-sequencing efforts, such as 1kGP, are providing a much more
comprehensive catalog of common variation (>1% MAF) in diverse
populations
Next-gen GWAS tools are leveraging this expanded catalog of variation
to drive a new wave of genetic discovery by enabling exploration of the
rare-variant hypothesis and higher resolution CNV research in a costeffective tools.
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Thank you!
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