ASHG 2017 Workshop Speaker Profiles - BGI

DNA Nanoball Sequencing technology improves sequencing data quality at a lower cost.

Radoje Drmanac, Ph.D. CTO, Complete Genomics

Abstract: DNA Nanoball Sequencing technology improves sequencing data quality at a lower cost DNA nanoball (DNB) arrays are prepared by linear DNA amplification using rolling circle replication in solution. DNB arrays are the most efficient and highest density patterned DNA arrays (<500nm pitch) enabling the lowest cost massively parallel NGS especially WGS. In addition, DNB arrays provide higher quality sequencing data than PCR-based DNA cluster arrays which suffer from sequence dropouts and amplification errors. Furthermore, advanced DNB arrays support any NGS application by various read architecture from SE50 to SE400+ or PE50 to PE200+. As an example, 90% of SE300 reads from good DNBs have zero errors. Or, overall discordance is <0.2% in the mapped PE200 reads. With further optimization of DNB array preparation and imaging we except to be the first to achieve $100 genome.

Biography: Dr. Radoje (Rade) Drmanac (http://www.rdrmanac.com) is one of the founders of the field of Genomics. Dr. Drmanac invented and led the development of massively parallel DNA sequencing using DNA nanoarrays and long fragment read (LFR) technologies. Currently he serves as Director and Chief Scientific Officer (CSO) at Complete Genomics, Inc. (CGI) that he co- founded in Silicon Valley (California) in 2005 to develop technologies for efficient and accurate individual genome sequencing (Science 2010, Nature 2012, Science 2012, Genome Research 2015, Hum Genomics 2016, Gigascience 2016, Cancer Res. 2017, Genet. Med. 2017). CGI was acquired by BGI (Shenzhen, China) in 2013 and Dr. Drmanac now serves as Senior VP of BGI. Earlier, he co-founded Hyseq in 1994, and served as Director until 2001. As SVP of research and CSO, he led Hyseq’s effort to discover and patent thousands of novel genes for its drug development pipeline. Prior to Hyseq, he was a group leader at US DOE Argonne National Labs (1991-1994) as part of Human Genome Project. He completed his postdoctoral studies in 1990 at ICRF in London. He started his career at the Center for Genetic Engineering (now IMGGI), in Belgrade, Serbia (1982-1988). He received his Ph.D. in Molecular Biology in 1988 at Belgrade University for the conception and pioneering development of the first massively parallel sequencing technology using DNA microarrays (Science 1993, Genomics 1989, Sci. Yugoslavica 1990). At the same university he received BS in Molecular Biology (1981).

The complex genetics of congenital heart disease.

Cecilia Lo, Ph.D Sargent Cheever Chair and Professor, Department of Developmental Biology, University of Pittsburgh School of Medicine

Abstract Modeling the genetic landscape of congenital heart disease with mouse forward genetics Congenital heart disease (CHD) is one of the most common birth defects, affecting up to 1% of live births. While a genetic etiology is indicated by increased recurrence risk, sporadic occurrences suggest the genetic etiology of CHD is complex. Insights into the complex genetics of CHD has emerged from a large-scale recessive mouse mutagenesis screen using noninvasive fetal ultrasound imaging for cardiovascular phenotyping. Screening of 100,000 fetal mice and mutation recovery using whole mouse exome sequencing analysis identified 100 genes causing a wide spectrum of CHD. Unexpectedly, many of the CHD genes encoded proteins that are direct protein-protein interactors, suggesting an interactome network may comprise the genomic context underlying the complex genetics of CHD pathogenesis. Indeed analysis of 8 mutant mouse lines with hypoplastic left heart syndrome (HLHS), one of the most severe CHD, revealed HLHS is genetically heterogeneous with an obligate multigenic etiology. Analysis of one HLHS mouse line showed a digenic etiology for HLHS, with modular phenotypes elicited genetically in a combinatorial fashion. These findings show the efficacy of mouse forward genetics for modeling complex genetics, findings with broad relevance not only for CHD, but also other human diseases.

Biography Dr. Cecilia Lo received her BS degree from Massachusetts Institute of Technology and her PhD from the Rockefeller University. She is currently Professor and Chair of the Department of Developmental Biology at the University of Pittsburgh School of Medicine, where she also holds the F Sargent Cheever Chair. Her laboratory has been pursuing the use of systems genetics with large scale mouse forward genetics to interrogate the genetic landscape of congenital heart disease (CHD). These studies have led to a previously unappreciated role for cilia in the pathogenesis of CHD, and new insights have also emerged on the complex genetics of CHD, findings that also have relevance for other human diseases. Work from her laboratory have been published in Nature, Nature Genetics, and other high profile journals.

Clinical exome sequencing in paediatrics: challenges and opportunities.

Avni Santani, Ph.D. FACMG Director, Division of Genomic Diagnostics, Children’s Hospital of Philadelphia

Abstract: With the explosion of genomic information and novel gene discoveries, clinical laboratories are faced with critical challenges in facilitating sensitive data interpretation. In particular, laboratories are faced with developing strategies that can incorporate data in the interpretation of genetic variants and review that variant classification over time. Dr. Santani will share insights in the integration of NGS data in clinical diagnostics, using exome sequencing as an example. She will address the development of a comprehensive interpretation pipeline for exome sequencing, discuss challenges with data interpretation, and present results from the exome sequencing program at Children’s Hospital of Philadelphia.

Biography Dr. Avni Santani, Ph.D, is an Assistant Professor of Clinical Pathology at the University of Pennsylvania and Director in the Division of Genomic Diagnostics at the Children’s Hospital of Philadelphia . She is also the Director of Clinical Laboratories, Strategic Partnerships and Innovation at the Center for Applied Genomics (CAG) where she oversees the clinical genomics program for rare pediatric disorders. Dr. Santani received her Master’s in Medical Molecular Genetics at the University of Aberdeen and her PhD in Genetics at Texas A&M University. She holds specialty board certifications in Clinical Molecular Genetics and Clinical Cytogenetics.

Under Dr. Santani’s leadership, the multi-disciplinary clinical program at CAG is focused on creating comprehensive genomics program for patients with rare pediatric disorders by forming strategic alliances with pharmaceutical companies, advancing gene discovery, developing comprehensive genetic tests, and developing innovative technologies and informatics tools. Dr. Santani is an experienced leader in molecular diagnostics with years of experience in clinical testing, genomics, strategy and laboratory administration. Her research focuses on leveraging advanced technology and informatics for the diagnosis of rare genetic disorders. Her work in the area of clinical genomics led to her receiving the Innovator of the Year Award (2015) by the Philadelphia Business Journal. She also is actively involved with several national working groups including a member of College of American Pathologists Next Generation Sequencing Project Team and The Association of Molecular Pathology Teaching and Education Committee.