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Company type | Genome Centre |
---|---|
Founded | 1998 |
Headquarters | , |
Area served | Biomedical Research |
Key people | Dr. Stephen W. Scherer, Scientific Director |
Services | Experimentation, Project consultation, Data analysis, Bioinformatics. |
Number of employees | 70 |
Parent | The Hospital for Sick Children |
Website | http://www.tcag.ca/ |
The Centre for Applied Genomics is a genome centre in the Research Institute of
The Hospital for Sick Children, and is affiliated with the
University of Toronto. TCAG also operates as a Science and Technology Platform of
Genome Canada
[1]. Research at TCAG focuses on the genetic and genomic basis of human variability, health and disease, including research on the genetics of
autism spectrum disorders and structural variation of the
human genome. The Centre is located in the
MaRS Discovery District in downtown
Toronto,
Canada.
The need for a centralized core facility for human genome research at SickKids Hospital prompted the establishment of The Centre for Applied Genomics (TCAG) in 1998. The Founding Director and Associate Director were Drs. Lap-Chee Tsui and Stephen W. Scherer, respectively. Dr. Scherer is now the Scientific Director. Dr. Tsui remains an ex officio member of the Scientific Advisory Board, having left SickKids in 2002 to become President and Vice-Chancellor of the University of Hong Kong.
Funding from the Canada Foundation for Innovation (CFI) enabled TCAG to form by consolidating existing core facilities including the Medical Research Council of Canada Genome Resource Facility, the Canadian Genetic Diseases Network (CGDN) large insert clone core, the CGDN DNA Sequencing Core and the SickKids Biotechnology Service DNA Sequencing and Synthesis labs. A genome-wide microsatellite genotyping laboratory at the Ottawa Health Research Institute led by Dr. Dennis Bulman was added. Subsequently, operational funding from the CIHR Genomics Special Projects panel provided for additional staff.
In 2001, a proposal entitled "Genome Resource Core Platform" was submitted to the then newly formed Genome Canada. This provided operational support, enhancing existing facilities and adding a mouse genotyping core at the University of Toronto led by Dr. Lucy Osborne. In 2002, SickKids built a new Affymetrix microarray facility. This core has quickly grown to become the largest such service centre in Canada and is in the top ten in North America [2].
In 2004, TCAG entered a second phase of development driven by a $12 million CFI/ Ontario Innovation Trust funded project entitled "Integrative Genomics for Health Research" [3], allowing for consolidation of the mouse genotyping core with the SickKids facilities. This award also supported the establishment of an "Ontario Population Genomics Repository" (OPGP) to be used as controls in studies of common diseases. To efficiently complete this project, TCAG partnered with Dr. John McLaughlin's group at Mount Sinai Hospital (Toronto).
In May, 2004, an application to the newly announced CFI Research Hospital Fund resulted in a $10.9 million dollar award to build out lab space and consolidate all operations on the 14th and 15th floors of the Toronto Medical Discovery Tower (TMDT) in the MaRS Discovery District. TCAG was the first occupant of TMDT (in August, 2005), quickly followed by other SickKids scientists. Most recently, investments in computer infrastructure from the 2003 CFI/ Ontario Innovation Trust competition have resulted in the establishment of new phases of the high-performance computing cluster (HPF) that is currently used by TCAG and many other users, to allow analysis of large genomic datasets arising from new microarray and sequencing technologies.
Since January, 2006, TCAG has been operating in large part on renewal funds from
Genome Canada, administered by the
Ontario Genomics Institute.
Current research at TCAG centres around large-scale projects performed by facility personnel, including support of Genome Canada projects, and a significant focus on the genetics of autism spectrum disorders and structural variation of the human genome.
Past research at TCAG is reflected by numerous peer-reviewed scientific publications. In the first quarter of 2008, TCAG Scientific Directors, Associate Scientists and staff co-authored 22 peer-reviewed manuscripts dependent in some way (either entirely, or in part) on the platform infrastructure, as documented in PubMed [4]. Since 2002, nearly 250 such papers have been published [5]. Support of other researchers worldwide is found in many similar publications, with at least 120 papers in scholarly journals, book chapters, or graduate thesis dissertations acknowledging support or use of database resources during 2007 alone [6]
A few of the most significant historical papers include:
TCAG was also integral to publications describing the decoding of human chromosome 7 [14], the discovery of large-scale copy number variation in the human genome [15] [16], and the analysis of the first diploid human genome sequence (with the J. Craig Venter Institute). [17]
As a Science and Technology Platform of
Genome Canada, TCAG currently supports nine large-scale projects, including research on
autism spectrum disorders, structural variation of the
human genome, integrative biology, conditional mouse mutagenesis, interactions of signaling molecules,
type I diabetes,
cancer stem cells,
Cystic Fibrosis, and
biodiversity, from Genome Canada's Competition III.
[18]
TCAG also hosts and curates websites and databases developed from supported projects, namely The Chromosome 7 Database, The Database of Genomic Variants
[19], the Segmental Duplication Database, the Autism Chromosome Rearrangement Database, and others
[20]. These databases contain publicly-available information.
TCAG employs a variety of genomic technologies to support different types of experimentation. These are organized into separate Core Facilities, with dedicated managers.
The DNA Sequencing and Synthesis Core Facility has a dedicated manager for DNA Synthesis. The DNA Sequencing component shares a manager with the Genetic and Statistical Analysis Core Facility. This latter manager is responsible for the genotyping functions within that facility.
The facility uses conventional capillary Sanger sequencing on Applied Biosystems 3730xl instruments, governed by a Laboratory Information Management System (LIMS). Additionally, next-generation sequencing (NGS) using the Illumina Genome Analyzer (Solexa 1G) and Applied Biosystems SOLiD instruments have been recently implemented. A key component of this facility is the use of high-performance computing and bioinformatics support for NGS analysis and assembly.
The
Oligonucleotide Synthesis component of this facility makes conventional, long (up to 120
bases) and modified
oligonucleotides, and purifies these by desalting, cartridge or high-performance liquid chromatography (
HPLC).
The
Microarray and Gene Expression Core Facility has a dedicated manager, and operates
Affymetrix and
Agilent technologies. All
Illumina technologies are contained within the Genetic Analysis Core Facility.
Affymetrix MegAllele and
Single Nucleotide Polymorphism (SNP)
microarrays,
Affymetrix
gene expression, tiling,
promoter and
exon
microarrays, and
Agilent
oligonucleotide
microarrays are all run. Additionally, there are a wide variety of analytical
software packages available for on-site data analysis.
The Cytogenomics and Genome Resources Core Facility has a single manager between these two functions. Cytogenomics includes karyotyping and spectral (SKY)
karyotyping (for
mouse,
human, and other species), fluorescent in situ hybridization (
FISH) mapping, transgenic insertion site mapping (G-to-FISH mapping) and clone labeling for
FISH experiments. The Genome Resources components includes a clone repository (Mammalian Gene Collection (MGC)
cDNA (
mouse and
human), genomic clones including human
bacterial artificial chromosomes (BACs)) and provides project consultation and design assistance (
annotation, database
queries, probe selection). It also provides
cDNA library screening and
quantitative PCR.
This Core Facility shares a manager (of the Genetic Analysis, or genotyping component) with the DNA Sequencing and Synthesis facility. The Statistical Analysis component has its own dedicated manager.
The Genetic Analysis area includes all Illumina technologies, including genome-wide (Infinium) and custom content (iSelect and GoldenGate) genotyping, methylation, microRNA, and gene expression microarrays. It also performs capillary-based genotyping ( Applied Biosystems Taqman and SNaPshot, microsatellites), custom genotyping (e.g. heteroduplex analysis), mouse genotyping (for cross progeny and genetic linkage analysis), and methylation analysis (for epigenetics research).
The Statistical Analysis component provides project consultation and
power analysis, statistical analysis (
genetic,
microarray, and
pathway data,
epidemiology,
population genetics), and
copy number variation analysis, as well as developing new statistical methods.
The Biobanking Core Facility has its own dedicated manager. It performs
white cell immortalization (from
blood) and banking,
fibroblast
culture and banking, culture and banking of other cell types including non-human cells,
genomic DNA preparation from
blood,
saliva,
tissues or
cells, and
whole-genome amplification (WGA).
TCAG is funded by several agencies, including the
Canada Foundation for Innovation (CFI),
Genome Canada through the
Ontario Genomics Institute, the
Ontario Ministry of Research and Innovation, and the
Wellcome Trust. Additionally, philanthropic donations are administered by
The Hospital for Sick Children Foundation, and specific research projects are funded by a wide variety of agencies and charitable foundations.
The Scientific Director of TCAG is Dr. Stephen W. Scherer, Senior Staff Scientist and Associate Chief of
The Hospital for Sick Children's Research Institute and a professor at the
University of Toronto.
[21]
TCAG is governed by a Scientific Management Committee, who meet regularly to discuss high-level strategic planning. The Scientific Management Committee consists of:
Dr. Osborne is located at the
University of Toronto, Dr. Bulman at the
Ottawa Health Research Institute, and the others at
The Hospital for Sick Children.
Since 2006, TCAG has appointed Associate Investigators, who are typically junior faculty members of a university or similar academic institution. These associates consult on their specific areas of expertise, and assist in identification and implementation of new technologies. At present, there are five Associate Investigators: Drs. Andy Boright (
UHN), Mary Shago (
SickKids), Esteban Parra (
UTM), Mark Silverberg (
MSH), and John Vincent (
CAMH).
High-level scientific oversight of TCAG's scientific mandate and operations is provided through an external Scientific Advisory Board (SAB). The SAB members are: