From Genomic Studies to Cytogenetics Research —

An Integrated and Standardised Solution

Dr. Mike Evans — Chief Executive

Today’s agenda

Welcome

Designing a genome-wide structural variant search for type 1 diabetes

loci — Stephen Rich, PhD

How to ensure the highest quality CNV results — Mike Evans, DPhil

Updates on ISCA Consortium and Database — David Ledbetter, PhD

Closing remarks

OGT - provides advanced clinical genetics solutions

- develops innovative molecular diagnostics

Clinical and Genomic SolutionsArray services and cytogenetics products

Technologies

For Molecular

Medicine

Biomarker DiscoveryGenomic- and protein-based diagnostics

IP Licensing

Clinical and Genomic Solutions

Cytogenetics

• CytoSure™ product range and service

Genomic services

• Genefficiency™ high throughput microarray services

Today’s agenda

Welcome

Designing a genome-wide structural variant search for type 1 diabetes

loci — Stephen Rich, PhD

How to ensure the highest quality CNV results — Mike Evans, DPhil

Updates on ISCA Consortium and Database — David Ledbetter, PhD

Closing remarks

Designing a Genome-wideStructural Variant Search for

Type 1 Diabetes Loci

Stephen S. Rich, PhD

November 4, 2010

High-quality, cost effective genomic services for the following

applications:

Service Application Target Market

aCGH Copy Number variation

(CNV) detection / analysis

- GWAS

- Cancer studies

- Molecular psychiatry

miRNA miRNA expression analysis - Biomarker studies

- Cancer research

- Expression studies

Methylation Detecting epigenetic events - Epigenetic studies

- Biomarker studies

Gene

expression

Gene expression analysis - Biomarker studies

- Expression studies

What is Genefficiency™ from OGT?

Reliably detect biologically significant CNVs

• Performance:

aCGH locates more chromosomal breakpoints at higher resolution than

other methods*

• Platform:

Agilent platform provides superior detection and quantification of CNVs.*

Superior sensitivity through long oligos (60mers)†

• People:

Our dedicated, experienced scientists are available for consultation and

support throughout your project

• Process Power: minimising technical variation

>2,000 samples per week capacity, with >40 QC checks on each sample

and proprietary LIMS, ensures quick delivery of high quality data

*Curtis, C. et al (2009) BMC Genomics 10, 588-610†Ionita-Laza, I. et al (2009) Genomics 93, 22-26

Genefficiency™ High-Throughput Services

OXFORD GENE TECHNOLOGY

SUCCESSFULLY COMPLETES

WORLD’S LARGEST COPY

NUMBER VARIATION STUDY

Oxford, UK, May 21, 2009 - Oxford

Gene Technology (OGT), the pioneer of

microarray-based technologies, has

successfully completed processing

more than 20,000 samples that

have been generated by the Wellcome

Trust Case Control Consortium

(WTCCC), the world’s largest CNV

study involving a collaboration of 24

leading human geneticists.

Customer satisfaction...

20,000 samples. 1,000 samples / week

―In order to characterise genetic variants,

reproducible performance and reliable processing

of the high resolution microarrays is essential. We

were pleased with OGT’s responsive approach

and attention to producing high quality data to tight

deadlines‖

Dr Matt Hurles, Wellcome Trust Sanger Institute.‖

LIMS provides full traceability at every stage

• Customised modules for: plate handling, unique array IDs, hybridisation oven and scanner

• QC on all reagents and consumables: digest and labelling mixes,

incubation block, clean-up kit, cot-1 solution and wash solutions

Time

DL

RS

*

Wk1 Wk190

0.1

0.2

0.3

0.4

0.5

GOOD

EXCELLENT

POORHeat

block

failure

Purification

module

failure

*DLRS –derivative log ratio spread

This metric is a measure of the quality of the data and hence confidence to detect and call CNV aberrations.

98% Pass rate of Control sample run on every plate for 19 weeks

DLR Spread of Control Samples

Quality Management System

• Quality management system has been

certified to

• ISO 9001:2008 (Quality management

systems)

• ISO 27001 (Information security)

• ISO 17025 (Laboratory services)

ISO 9001

FS 561156

The OGT aCGH design process

aCGH arrays

All possible human genome probes

OligomeTM database

Further selection based on OGT probe rating

and desired coverage and content

Selection based on specificity, Tm, GC, etc.

Design & hyb two different aCGH arrays

Optimised aCGH design

Selection of best performing

probes based on

experimental results

Optimised array design for genomic services

and cytogenetic products

CytoSure cytogenetics range

high quality data

meaningful results

standardisation

• Arrays

• ISCA and Syndrome Plus

• Chromosome X

• Aneuploidy

• DMD

• New! ISCA UPD

• Labelling kit

• Software

• Oligome custom arrays

• Hyb buffers, backing plates

• Full automation options

CytoSure™ Interpret Software - Features

• Data visualisation

meaningful results

CytoSure™ Interpret Software - Features

• Data visualisation

• Automated aberration detection

meaningful results

CytoSure™ Interpret Software - Features

• Data visualisation

• Automated aberration detection

• Annotation tracks

meaningful results

CytoSure™ Interpret Software - Features

• Data visualisation

• Automated aberration detection

• Annotation tracks

• Report generation

• Batch processing

• Data management

• ...and many more – a large number as a result of customer feedback – providing

flexibility in data analysis e.g. User-defined annotation tracks

Syndromes

ExonsGenes

Recomb.

HotspotsCNVs

ConfirmationDecipher

meaningful results

CytoSure™ Interpret Software - Features

• Data visualisation

• Automated aberration detection

• Annotation tracks

• Report generation

meaningful results

CytoSure™ Interpret Software - Features

• Data visualisation

• Automated aberration detection

• Annotation tracks

• Report generation

• Batch processing

• Data management

meaningful results

CytoSure™ Interpret Software - Features

• Data visualisation

• Automated aberration detection

• Annotation tracks

• Report generation

• Batch processing

• Data management

• ...and many more – a large number as a result of customer feedback – providing

flexibility in data analysis e.g. User-defined annotation tracks

meaningful results

Today’s agenda

Welcome

Designing a genome-wide structural variant search for type 1 diabetes

loci — Stephen Rich, PhD

How to ensure the highest quality CNV results — Mike Evans, Dphil

Updates on ISCA Consortium and Database — David Ledbetter, PhD

Closing remarks

“Our recommendation based on current evidence is to offer CMA as the first-tier genetic test, in place of G-banded karyotype, for

patients with unexplained DD/ID, ASD, or MCA.” ISCA Consortium

Yield for clinically significant CNVs in autism/ASD = 5-10%.

(may impact prognosis, identify and direct management

of medical co-morbidities, recurrence risk counseling).

Published September 2010

Today’s agenda

Welcome

Designing a genome-wide structural variant search for type 1 diabetes

loci — Stephen Rich, PhD

How to ensure the highest quality CNV results — Mike Evans, DPhil

Updates on ISCA Consortium and Database — David Ledbetter, PhD

Closing remarks & lunch

CytoSure — excellence from sample to result

• Optimized, double-validated array content — regularly updated to

ISCA specifications

• Reliable detection of CNV and UPD on a single array — CytoSure

ISCA UPD array

• Effortless data analysis — easy-to-use, class-leading software

• Expert, high-throughput cytogenetics aCGH service — CytoSure

Services

The complete solution for cytogenetics — arrays (product or custom),

software, labelling, reagents, automation, services

OGT can help!

OGT has made major investments in infrastructure and software to support disease and cytogenetics research…

Run your samples using our HT facility

• OGT has an unparalleled track record in delivering high quality data for CNV, methylation, miRNA and gene expression analysis

Design your perfect array

• OGT’s array design expertise and double-validated probes can help you design a custom array to suit your specific needs

Choose your ideal cytogenetics products

• CytoSure delivers the complete solution for cytogenetics — from sample to result

AcknowledgementsOGT Collaborators and Customers

Thank you

www.ogt.co.uk

Visit us at booth 1307 for more information