High coverage of common and rare variants to detect disease associations in Han Chinese populations

1. Axiom®
Genome-Wide CHB 1 & CHB 2 Array Plate Set
The highest coverage of rare and common variants for association studies in Han Chinese populations
Highlights
n 1.2 million SNPs selected from GWAS in Han
Chinese populations
n Comprehensive genotype-tested SNPs including
maximized rare and common allele coverage
n Focus on SNPs with strong disease associations
and functional relevance
n Cost- and analysis-efficient design using only highly
informative CHB markers to avoid redundancy
n Fully automatable with quick assay turnaround time
n Low running costs enable highly powered studies
n Flexible, automation-friendly data analysis software
for simplified data management
Array design/SNP selection
All of the content for Axiom®
Genome-Wide (GW) CHB 1
& CHB 2 Array Plate Set was selected from Axiom®
Genomic
Database, which contains genotype-tested markers derived
from various public sources, including the International HapMap
Project, the Single Nucleotide Polymorphism Database (dbSNP),
and the 1000 Genomes Project. Each marker was tested
extensively to ensure robust detection of the minor allele
with stringent performance criteria in the Axiom®
Assay.
Our genotype testing program gives us uniquely detailed
data on population-specific linkage disequilibrium and
haplotypes. This allows us to be highly efficient when selecting
tagging SNPs for high genomic coverage. By avoiding marker
redundancy and uninformative markers, we minimize the
numbers of SNPs needed to achieve genomic coverage.
SNPs were selected to provide maximum genome-wide
coverage including: chromosomes X and Y, mitochondrial
SNPs, cSNPs (coding SNPs), and indels (see Table 1).
Also included on the array are SNPs within functionally
relevant coding and untranslated regions (UTR) including
markers for ADME and disease-associated SNPs. SNPs
were selected from disease annotation databases such as
Gene Ontology (GO) for the cardiovascular system, Sanger
Cancer Gene Census, PharmaADME, SNPs within the Major
Histocompatibility Complex (MHC) region on chromosome
6, and SNPs originating from the National Human Genome
Research Institute (NHGRI) Catalog of Published Genome-
Wide Association Studies (see Table 1).
Comprehensive genomic coverage
The 1.2 million SNPs in Axiom Genome-Wide CHB 1 & CHB 2
Array Plate Set were chosen to deliver comprehensive coverage
of rare and common alleles in Han Chinese populations.
Axiom®
Genome-Wide (GW) CHB 1 Array Plate was designed
for high genomic coverage of common alleles, while Axiom®
Genome-wide (GW) CHB 2 Array Plate focuses on rare variants.
Axiom GW CHB 2 Array Plate was specifically designed to
supplement the content of the Axiom GW CHB 1 Array Plate.
This complementary nature is shown in Table 2.
Data Sheet
Table 1: Breakdown of SNPs by biological relevance.
Biological category
No. SNPs
Axiom
GW CHB 1
Array Plate
No. SNPs
Axiom GW
CHB 1 & CHB 2
Array Plate Set
cSNPs-nonsynonymous 4,225 10,560
cSNPs-synonymous 3,243 8,422
Splicing and UTR 7,641 20,538
Chromosome X 12,545 36,841
Chromosome Y 1,613 2,460
Indels 3,112 3,826
Mitochondrial 217 304
ADME 3,723 7,886
Genic 277,429 552,684
Inflammation and
immunity pathways
4,387 12,009
MHC 1,873 4,229
Cardiovascular N/A 14,293
NHGRI
disease-associated
2,114 2,424
Sanger Cancer
Gene Census
N/A 16,781
Total SNPs 640,674 1,282,446

2. Table 2: Genomic coverage of Axiom®
GW CHB 1 Array Plate and
Axiom®
GW CHB 1 & CHB 2 Array Plate Set. Pairwise genomic coverage
at r2
>0.8 for SNPs in the 1000 Genomes Project Phase 1 integrated
release Dec 2011; Han Chinese in Beijing (CHB), Han Chinese South (CHS),
and Japanese in Tokyo (JPT) alleles.
Axiom GW
CHB 1
Array Plate
Axiom GW CHB
1 & CHB 2 Array
Plate Set
Other
commercially
available
Chinese array
Population
MAF
>2%
MAF
>5%
MAF
>2%
MAF
>5%
MAF
>2%
MAF
>5%
CHB 66% 77% 80% 86% 72% 79%
CHS 64% 75% 79% 86% 72% 79%
JPT 64% 72% 78% 84% 72% 78%
Superior assay performance
As shown in Table 3, Axiom®
Genome-Wide CHB 1 & CHB 2
Array Plate Set has superior technical performance offering high
confidence for genome-wide association studies.
Table 3: Performance achieved by Axiom GW CHB 1 & CHB 2
Array Plate Set. Calculated based on 190 Chinese and Japanese
HapMap samples.
Performance metric Specification
Average SNP call rate >99%
Average HapMap concordance >99.5%
Average reproducibility >99.7%
Ordering information
Part number Description Details
901843 Axiom®
Genome-Wide CHB 1
& CHB 2 Array Set Bundle
Sufficient for processing 96 gDNA samples, includes:
n
One Axiom Genome-Wide CHB 1 96-Array Plate
n
One Axiom Genome-Wide CHB 2 96-Array Plate
n
Two Axiom®
2.0 Reagent Kits
n
Two Axiom®
GeneTitan®
Consumables Kits
901764 Axiom®
Genome-Wide CHB 1 Array Plate Contains one Axiom Genome-Wide CHB 1 96-Array Plate
901842 Axiom®
Genome-Wide CHB 2 Array Plate Contains one Axiom Genome-Wide CHB 2 96-Array Plate
901758 Axiom®
2.0 Reagent Kit Contains all reagents (except isopropanol) required to process 96 gDNA samples
901606 Axiom®
GeneTitan®
Consumables Kit Contains all GeneTitan®
Instrument consumables required to process one Axiom®
Array Plate
0000740 Axiom®
Genotyping Services
Sample processing and data generation services for gDNA samples (minimum 1,000
samples) using the Axiom Genotyping Solution
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P/N DNA01393 Rev. 1
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Quick assay turnaround time
Axiom Genome-Wide CHB 1 & CHB 2 Array Plate Set is part
of Axiom®
Genotyping Solution, which uses Axiom®
2.0 Assay.
The assay is fully automatable on Affymetrix GeneTitan®
Multi-
Channel Instrument for array processing.
n Minimal operator intervention – load consumables, press start,
then view analysis
n High throughput – instrument operates overnight and can
manage over 760 samples/week
n Time efficient – less than 2.5 hours of hands-on time per
96 samples
Flexible data analysis software
Integrate Microsoft Windows GUI-based Genotyping Console™
Software (GTC) or automation-friendly command line-based
Affymetrix Power Tools for completing the primary genotyping
analysis. The flexible software workflow with simplified data
management allows you to easily share your results and seamlessly
integrate with third-party software packages.
Sample types supported
n gDNA from fresh blood
n gDNA from saliva (collected using Oragene®
DNA collection kits
from DNA Genotek)
n Whole-genome amplified (WGA) DNA (amplified from gDNA
using QIAGEN Repli-g®
kits)