Conference Program - ABRF 2011 - Association of Biomolecular ...

Workshop Session AbstractsWorkshop SessionAbstracts(W1) The Diagnostics Core Facility: Harvestingthe Promise of Personalized Medicine(W1-1) Win on Sunday, Sell on Monday: From theExome Sequencing of One Boy to the Delivery ofClinical DiagnosticsM.R. TschannenHuman and Molecular Genetics Center, Department ofPhysiology, Medical College of Wisconsin, Milwaukee, WI,United StatesFor several years, there have been discussions about using bothSanger and whole genome sequencing in clinical practice. In late2009, the Medical College of Wisconsin initiated the infrastructureto streamline the delivery of current and emerging DNA technologiesinto state-of-the-art molecular diagnostics. The online publication ofour initial case in Genetics of Medicine in late 2010 further intensifiedour efforts in this endeavor. However, being relatively new to thefield of NextGen sequencing, we began with the addition of Sangerdiagnostic sequencing to our already successful research core, whichat that point had been in operation for almost ten years. This was agreat undertaking, as typically, independent research laboratoriesperforming cutting-edge science lack the financial resources andbreadth of experience to launch their custom product or applicationto the diagnostic industry. An independent research laboratory is ableto resolve these shortages by partnering with a core laboratory staffedwith diagnostic expertise. Due to our lack of diagnostic experience, wequickly aligned the research core to a consortium of individuals withclinical experience to allow us to benefit from established diagnosticfacilities on campus. Difficulties faced at the onset of diagnostic startupwere many, including large issues such as accreditation program (CAPvs. CLIA), SOP generation and validation, competency and proficiencytesting, and reimbursement, as well as smaller problems like semiannualpipette calibration, temperature monitoring, and inventorycontrol. The purpose of this talk is to give insight into efficient ways toresolve these problems, both large and small, and transform a decadeor more of research expertise into a viable diagnostic laboratory.(W1-2) Chromosomal Microarray Analysis in theClinicL.D. WhiteMicroarray Core, Baylor College of Medicine, Houston, TX,United StatesCurrent Array Comparative Genomic Hybridization (aCGH) orChromosomal Microarray Analysis (CMA) performed at BaylorCollege of Medicine utilizes the latest microarray technology to detectunbalanced chromosome abnormalities associated with over 210 clinicaldisorders with exon by exon coverage of over 1,700 genes. We haveperformed approximately 35,000 postnatal CMA tests. Additionally,inclusive of our reported experience with 300 prenatal cases (PMID19012303), we now have CMA results on approximately 800 clinicalprenatal samples. This talk will cover the utility CMA for chromosomalabnormality detection in the clinical lab as well as development anddeployment of clinical tests from the core lab perspective.(W1-3) Whole Genome Sequencing in the ClinicalLaboratoryT. Hambuch, M. Laurent, B. Sickler, A. Liao, P. Cotter,S. Jain, Y. Lyan, J. Bernd, J.O. Daniel, P. Poggio, M. Ross,D. BentleyIllumina Clinical Services Laboratory, San Diego, CA, UnitedStatesThe advent of routine whole genome sequencing creates an opportunityto provide an accurate, comprehensive and cost-effective catalogue ofgermline variation for an individual. The process of sequencing anddelivering genomes for individual use must be driven by clinical andeducational opportunities balanced by addressing ethical concerns.Using guidelines issued from professional and accrediting agenciesas well as an independent ethics board, we developed and launchedindividual genome sequencing (IGS) as a physician-led service. Aphysician orders the sequence and obtains informed consent from theindividual; the sample is sequenced within a CLIA certified laboratoryand after a series of quality checks the sequence is returned to thephysician for communication back to the individual. The sequencingplatform and process were validated for accuracy and precision, andaccredited following review by a College of American Pathologist(CAP) inspection team. Each individual genome is sequenced at >30fold coverage using paired-end reads of 100 base pairs. Resultingsequence information is provided for >93% of the NCBI36 genome, theremainder being mostly recently duplicated repeats where ambiguousread alignment is not permitted in our ELAND analysis. On average, wedetect over 3 million SNPs most of which are previously documentedin dbSNP129. The overall accuracy of our base calling is measured as>99.99% and the accuracy for SNP calling is >99.7% based on multiplemethodlogical assessments. The aim of the Illumina Clinical ServicesLaboratory is to make Individual Genome Sequencing accurate,accessible and clinically relevant for physicians and patients through afully accredited process. Here we have established baseline processes,tools, and policies to maximize the benefit to patients and minimizepotential misuse. Additionally, our ongoing efforts to develop clinicallyrelevant interpretation tools for physicians are described in a separateabstract (see M. Ross). Individual Genome Sequencing has the capacityto replace current genetic testing with a near-complete description ofthe sequence of an individual. Considering this potential, it is essentialto engage policy makers and ethicists so that appropriate policiesare developed around information access and use of whole genomeinformation.44 • ABRF 2011 — Technologies to Enable Personalized Medicine