1. From Genomic Studies to Cytogenetics Research — An Integrated and Standardised Solution Dr. Mike Evans — Chief Executive

2. 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

3. OGT - provides advanced clinical genetics solutions - develops innovative molecular diagnostics Clinical and Genomic Solutions Array services and cytogenetics products Technologies For Molecular Medicine Biomarker Discovery Genomic- and protein-based diagnostics IP Licensing

4. Clinical and Genomic Solutions Cytogenetics CytoSure™ product range and service Genomic services Genefficiency™ high throughput microarray services

5. 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

6. Designing a Genome-wide Structural Variant Search for Type 1 Diabetes Loci Stephen S. Rich, PhD November 4, 2010

18. What is Genefficiency™ from OGT? High-quality, cost effective genomic services for the following applications:

19. 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

20. 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.

21. Customer satisfaction... “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.” 20,000 samples. 1,000 samples / week

22. 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

23. DLR Spread of Control Samples 0.5 Heat block failure 0.4 POOR Purification module failure 0.3 GOOD DLRS* 0.2 EXCELLENT 0.1 0 Wk1 Wk19 Time 98% Pass rate of Control sample run on every plate for 19 weeks *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.

24. 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

25. The OGT aCGH design process All possible human genome probes Selection based on specificity, Tm, GC, etc. OligomeTM database Further selection based on OGT probe rating and desired coverage and content aCGH arrays Design & hyb two different aCGH arrays Selection of best performing probes based on experimental results Optimised aCGH design Optimised array design for genomic services and cytogenetic products

27. ISCA and Syndrome Plus

28. Chromosome X

29. Aneuploidy

30. DMD

31. New! ISCA UPD

32. Labelling kit

33. Software

34. Oligome custom arrays

35. Hyb buffers, backing plates

36. Full automation options meaningful results  standardisation

37. CytoSure™ Interpret Software - Features Data visualisation  meaningful results

38. CytoSure™ Interpret Software - Features Data visualisation Automated aberration detection  meaningful results

39. CytoSure™ Interpret Software - Features Data visualisation Automated aberration detection Annotation tracks  meaningful results

40. 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 Syndromes Genes Exons Recomb. Hotspots CNVs Decipher Confirmation

41. CytoSure™ Interpret Software - Features Data visualisation Automated aberration detection Annotation tracks Report generation  meaningful results

42. CytoSure™ Interpret Software - Features Data visualisation Automated aberration detection Annotation tracks Report generation Batch processing Data management  meaningful results

43. 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

44. 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

49. “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).

50. Published September 2010

72. 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

73. 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

74. 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

75. AcknowledgementsOGT Collaborators and Customers

76. Thank you www.ogt.co.uk Visit us at booth 1307 for more information