The Centre for Applied Genomics
Encyclopedia
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 Innovation Centre of Genome Canada, with an emphasis on next-generation sequencing (NGS) and bioinformatics
support. Research at TCAG focuses on the genetic
and genomic basis of human variability, health and disease, including research on the genetics of autism spectrum disorder and structural variation of the human genome
. The Centre is located in the MaRS Discovery District
in downtown Toronto
, Canada
.
and Stephen W. Scherer
, respectively. Dr. Scherer is now the Scientific Director.
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.
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", 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. Further enhancements to the TCAG infrastructure will be supported by a $10.7 million renewal grant from CFI's Leading Edge Fund competition, entitled "Integrative Genomics for Health Research - Phase II", awarded in June 2009.
From January, 2006, through June, 2011, TCAG operated in large part on renewal funds from Genome Canada, administered by the Ontario Genomics Institute.
. Service work is also performed for over 600 other academic, private sector and government labs each year, drawn from 30 different countries and spanning a wide variety of research disciplines.
Past research at TCAG is reflected by numerous peer-reviewed scientific publications. In 2008, TCAG Scientific Directors, Associate Scientists and staff co-authored 58 peer-reviewed manuscripts dependent in some way (either entirely, or in part) on the platform infrastructure, as documented in PubMed
. Since 2002, over 270 such papers have been published. Support of other researchers worldwide is found in many similar publications, with at least 145 papers in scholarly journals, book chapters, or graduate thesis dissertations acknowledging support or use of database resources during 2008 alone.
Historical papers include:
TCAG was also integral to publications describing the decoding of human chromosome 7, the discovery of large-scale copy number variation in the human genome
, and the analysis of the first diploid human genome
sequence (with the J. Craig Venter Institute).
, integrative biology, conditional mouse mutagenesis, interactions of signaling molecules, type I diabetes, cancer stem cells, Cystic Fibrosis
, biodiversity
, structural biology
, and stem cells, from Genome Canada's Competition III, New Technology Development and Applied Genomics Research in Bioproducts or Crops (ABC) competitions. The Centre is now working with applicants in the Large-Scale Applied Research Project and Advancing Technology Innovation Through Discovery competitions.
TCAG employs a variety of genomic technologies to support different types of experimentation. These are organized into separate Core Facilities, with dedicated managers. An integrated Bioinformatics
team assists with data handling and analysis, and develops new algorithms and analytical methods.
3730xl instruments, governed by a Laboratory Information Management System (LIMS). Additionally, next-generation sequencing (NGS) using Illumina
HiSeq 2000 and HiScan SQ instruments, five Applied Biosystems
SOLiD instruments, and a 454
/Roche
GS-FLX Titanium instrument is performed. A key component of this facility is the use of high-performance computing and bioinformatics
support for NGS analysis.
The Oligonucleotide Synthesis component of this facility makes conventional, long (up to 120 bases) and modified oligonucleotide
s, and purifies these by desalting, cartridge or high-performance liquid chromatography (HPLC
).
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 is a wide variety of analytical software packages available for on-site data analysis.
(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 chromosome
s (BACs)) and provides project consultation and design assistance (annotation, database queries
, probe selection). It also provides cDNA library
screening and quantitative PCR.
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, microsatellite
s), 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.
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).
(CFI), Genome Canada through the Ontario Genomics Institute, the Ontario Ministry of Research and Innovation. 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.
, Senior Staff Scientist in The Hospital for Sick Children's Research Institute, Director of the McLaughlin Centre, and a professor at the University of Toronto
.
Drs. Bader and Brudno are located at the University of Toronto
, and the others at The Hospital for Sick Children. The committee also includes three ex officio members: the Assistant Director, Facility Manager, and a representative from the Ontario Genomics Institute.
), Mary Shago (SickKids), Mark Silverberg (MSH
), James Stavropoulos (SickKids), Michael Taylor (SickKids), and John Vincent (CAMH
).
The Ontario Genomics Institute (OGI) and Genome Canada also provide ex officio members.
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
. TCAG also operates as a Science and Technology Innovation Centre of Genome Canada, with an emphasis on next-generation sequencing (NGS) and bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
support. Research at TCAG focuses on the genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
and genomic basis of human variability, health and disease, including research on the genetics of autism spectrum disorder and structural variation of the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
. The Centre is located in the MaRS Discovery District
MaRS Discovery District
MaRS Discovery District is a not-for-profit corporation founded in Toronto in 2000. Its stated goal is to commercialize publicly funded medical research with the help of local private enterprises and as such is a public-private partnership....
in downtown Toronto
Toronto
Toronto is the provincial capital of Ontario and the largest city in Canada. It is located in Southern Ontario on the northwestern shore of Lake Ontario. A relatively modern city, Toronto's history dates back to the late-18th century, when its land was first purchased by the British monarchy from...
, Canada
Canada
Canada is a North American country consisting of ten provinces and three territories. Located in the northern part of the continent, it extends from the Atlantic Ocean in the east to the Pacific Ocean in the west, and northward into the Arctic Ocean...
.
History
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 TsuiLap-Chee Tsui
Professor Lap-chee Tsui, OC, O.Ont is a Chinese-Canadian geneticist and currently the Vice-Chancellor and President of the University of Hong Kong.-Personal life:Tsui was born in Shanghai...
and Stephen W. Scherer
Stephen W. Scherer
Stephen Wayne Steve Scherer, PhD, DSc, FRSC , is a Canadian scientist, whose research has revolutionized the understanding of genetic variation in human disease. He obtained his PhD at the University of Toronto under Professor Lap-chee Tsui, discoverer of the cystic fibrosis gene...
, respectively. Dr. Scherer is now the Scientific Director.
Canada Foundation for Innovation
Created by the Government of Canada in 1997, the Canada Foundation for Innovation strives to build our nation’s capacity to undertake world-class research and technology development to benefit Canadians...
(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
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
Core and the SickKids Biotechnology Service DNA Sequencing
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
and Synthesis labs. A genome-wide microsatellite genotyping
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
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
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
core at the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
led by Dr. Lucy Osborne. In 2002, SickKids built a new Affymetrix
Affymetrix
Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...
microarray
Microarray
A microarray is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening methods.Types of microarrays include:...
facility. This core has quickly grown to become the largest such service centre in Canada and is in the top ten in North America.
In 2004, TCAG entered a second phase of development driven by a $12 million CFI
Canada Foundation for Innovation
Created by the Government of Canada in 1997, the Canada Foundation for Innovation strives to build our nation’s capacity to undertake world-class research and technology development to benefit Canadians...
/Ontario Innovation Trust funded project entitled "Integrative Genomics for Health Research", allowing for consolidation of the mouse genotyping
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
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)
Mount Sinai Hospital (Toronto)
Mount Sinai Hospital is a hospital in Toronto, Ontario, Canada. Although it is physically linked by bridges and tunnels to two University Health Network hospitals , Mount Sinai is an independently operated facility...
.
In May, 2004, an application to the newly announced CFI
Canada Foundation for Innovation
Created by the Government of Canada in 1997, the Canada Foundation for Innovation strives to build our nation’s capacity to undertake world-class research and technology development to benefit Canadians...
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
MaRS Discovery District
MaRS Discovery District is a not-for-profit corporation founded in Toronto in 2000. Its stated goal is to commercialize publicly funded medical research with the help of local private enterprises and as such is a public-private partnership....
. 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
Canada Foundation for Innovation
Created by the Government of Canada in 1997, the Canada Foundation for Innovation strives to build our nation’s capacity to undertake world-class research and technology development to benefit Canadians...
/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
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
and sequencing
DNA sequencing
DNA sequencing includes several methods and technologies that are used for determining the order of the nucleotide bases—adenine, guanine, cytosine, and thymine—in a molecule of DNA....
technologies. Further enhancements to the TCAG infrastructure will be supported by a $10.7 million renewal grant from CFI's Leading Edge Fund competition, entitled "Integrative Genomics for Health Research - Phase II", awarded in June 2009.
From January, 2006, through June, 2011, TCAG operated in large part on renewal funds from Genome Canada, administered by the Ontario Genomics Institute.
Research
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 genomeHuman genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
. Service work is also performed for over 600 other academic, private sector and government labs each year, drawn from 30 different countries and spanning a wide variety of research disciplines.
Past research at TCAG is reflected by numerous peer-reviewed scientific publications. In 2008, TCAG Scientific Directors, Associate Scientists and staff co-authored 58 peer-reviewed manuscripts dependent in some way (either entirely, or in part) on the platform infrastructure, as documented in PubMed
PubMed
PubMed is a free database accessing primarily the MEDLINE database of references and abstracts on life sciences and biomedical topics. The United States National Library of Medicine at the National Institutes of Health maintains the database as part of the Entrez information retrieval system...
. Since 2002, over 270 such papers have been published. Support of other researchers worldwide is found in many similar publications, with at least 145 papers in scholarly journals, book chapters, or graduate thesis dissertations acknowledging support or use of database resources during 2008 alone.
Historical papers include:
- Discovery of genes involved in predisposition to medulloblastomaMedulloblastomaMedulloblastoma is a highly malignant primary brain tumor that originates in the cerebellum or posterior fossa.Previously, medulloblastomas were thought to represent a subset of primitive neuroectodermal tumor of the posterior fossa...
(Michael Taylor and James Rutka with TCAG support) - Gene identification in Shwachman-Diamond syndrome (with Johanna Rommens and others)
- Gene identification in Lafora EpilepsyEpilepsyEpilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
(with Berge Minassian) and its canine counterpart - A disease-relevant MECP2 isoform involved in Rett SyndromeRett syndromeRett syndrome is a neurodevelopmental disorder of the grey matter of the brain that almost exclusively affects females. The clinical features include small hands and feet and a deceleration of the rate of head growth . Repetitive hand movements, such as wringing and/or repeatedly putting hands into...
- Involvement of the SUMO4 gene in type I diabetes
- Severe expressive-language delay related to duplication of the Williams–BeurenWilliams syndromeWilliams syndrome is a rare neurodevelopmental disorder characterized by a distinctive, "elfin" facial appearance, along with a low nasal bridge; an unusually cheerful demeanor and ease with strangers; developmental delay coupled with strong language skills; and cardiovascular problems, such as...
locusLocus (genetics)In the fields of genetics and genetic computation, a locus is the specific location of a gene or DNA sequence on a chromosome. A variant of the DNA sequence at a given locus is called an allele. The ordered list of loci known for a particular genome is called a genetic map...
TCAG was also integral to publications describing the decoding of human chromosome 7, the discovery of large-scale copy number variation in the human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
, and the analysis of the first diploid human genome
Human genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
sequence (with the J. Craig Venter Institute).
Genome Canada Projects
As a Science and Technology Innovation Centre of Genome Canada, TCAG currently supports numerous large-scale projects, including research on autism spectrum disorders, structural variation of the human genomeHuman genome
The human genome is the genome of Homo sapiens, which is stored on 23 chromosome pairs plus the small mitochondrial DNA. 22 of the 23 chromosomes are autosomal chromosome pairs, while the remaining pair is sex-determining...
, integrative biology, conditional mouse mutagenesis, interactions of signaling molecules, type I diabetes, cancer stem cells, Cystic Fibrosis
Cystic fibrosis
Cystic fibrosis is a recessive genetic disease affecting most critically the lungs, and also the pancreas, liver, and intestine...
, biodiversity
Biodiversity
Biodiversity is the degree of variation of life forms within a given ecosystem, biome, or an entire planet. Biodiversity is a measure of the health of ecosystems. Biodiversity is in part a function of climate. In terrestrial habitats, tropical regions are typically rich whereas polar regions...
, structural biology
Structural biology
Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules, especially proteins and nucleic acids, how they acquire the structures they have, and how alterations in their structures affect their function...
, and stem cells, from Genome Canada's Competition III, New Technology Development and Applied Genomics Research in Bioproducts or Crops (ABC) competitions. The Centre is now working with applicants in the Large-Scale Applied Research Project and Advancing Technology Innovation Through Discovery competitions.
Databases
TCAG also hosts and curates websites and databases developed from supported projects, namely The Chromosome 7 Database, The Database of Genomic Variants, the Segmental Duplication Database, the Autism Chromosome Rearrangement Database, and others. These databases contain publicly-available information.Core Facilities
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
team assists with data handling and analysis, and develops new algorithms and analytical methods.
DNA Sequencing and Synthesis
The facility uses conventional capillary Sanger sequencing on Applied BiosystemsApplied Biosystems
Applied Biosystems, Inc. started as GeneCo , was the name of a pioneer biotechnology company founded in 1981 in Foster City, California, in the San Francisco Bay Area...
3730xl instruments, governed by a Laboratory Information Management System (LIMS). Additionally, next-generation sequencing (NGS) using Illumina
Illumina (company)
Illumina, Inc. is a company incorporated in April 1998 that develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function. Using its technologies, the company provides a line of products and services that serve the sequencing, genotyping and...
HiSeq 2000 and HiScan SQ instruments, five Applied Biosystems
Applied Biosystems
Applied Biosystems, Inc. started as GeneCo , was the name of a pioneer biotechnology company founded in 1981 in Foster City, California, in the San Francisco Bay Area...
SOLiD instruments, and a 454
454 Life Sciences
454 Life Sciences, is a biotechnology company based in Branford, Connecticut. It is a subsidiary of Roche, and specializes in high-throughput DNA sequencing.-History and Major Achievements:...
/Roche
Roche Diagnostics
Roche Diagnostics Division is a subsidiary of Hoffmann-La Roche which manufactures equipment and reagents for research and medical diagnostic applications. Internally, it is organized into five major business areas: Roche Applied Science, Roche Professional Diagnostics, Roche Diabetes Care, Roche...
GS-FLX Titanium instrument is performed. A key component of this facility is the use of high-performance computing and bioinformatics
Bioinformatics
Bioinformatics is the application of computer science and information technology to the field of biology and medicine. Bioinformatics deals with algorithms, databases and information systems, web technologies, artificial intelligence and soft computing, information and computation theory, software...
support for NGS analysis.
The Oligonucleotide Synthesis component of this facility makes conventional, long (up to 120 bases) and modified oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
s, and purifies these by desalting, cartridge or high-performance liquid chromatography (HPLC
High-performance liquid chromatography
High-performance liquid chromatography , HPLC, is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry and analytical chemistry to identify, quantify and purify the individual components of the mixture.HPLC typically utilizes different types of stationary...
).
Microarray and Gene Expression
The MicroarrayMicroarray
A microarray is a multiplex lab-on-a-chip. It is a 2D array on a solid substrate that assays large amounts of biological material using high-throughput screening methods.Types of microarrays include:...
and Gene Expression Core Facility has a dedicated manager, and operates Affymetrix
Affymetrix
Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...
and Agilent technologies. All Illumina
Illumina (company)
Illumina, Inc. is a company incorporated in April 1998 that develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function. Using its technologies, the company provides a line of products and services that serve the sequencing, genotyping and...
technologies are contained within the Genetic Analysis Core Facility. Affymetrix
Affymetrix
Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...
MegAllele and Single Nucleotide Polymorphism
Single nucleotide polymorphism
A single-nucleotide polymorphism is a DNA sequence variation occurring when a single nucleotide — A, T, C or G — in the genome differs between members of a biological species or paired chromosomes in an individual...
(SNP) microarrays
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
, Affymetrix
Affymetrix
Affymetrix is a company that manufactures DNA microarrays; it is based in Santa Clara, California, United States. The company was founded by Dr. Stephen Fodor in 1992. It began as a unit in Affymax N.V...
gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
, tiling, promoter and exon
Exon
An exon is a nucleic acid sequence that is represented in the mature form of an RNA molecule either after portions of a precursor RNA have been removed by cis-splicing or when two or more precursor RNA molecules have been ligated by trans-splicing. The mature RNA molecule can be a messenger RNA...
microarrays
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
, and Agilent oligonucleotide
Oligonucleotide
An oligonucleotide is a short nucleic acid polymer, typically with fifty or fewer bases. Although they can be formed by bond cleavage of longer segments, they are now more commonly synthesized, in a sequence-specific manner, from individual nucleoside phosphoramidites...
microarrays
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
are all run. Additionally, there is a wide variety of analytical software packages available for on-site data analysis.
Cytogenomics and Genome Resources
The Cytogenomics and Genome Resources Core Facility has a single manager between these two functions. Cytogenomics includes karyotyping and spectral (SKY) karyotypingKaryotype
A karyotype is the number and appearance of chromosomes in the nucleus of an eukaryotic cell. The term is also used for the complete set of chromosomes in a species, or an individual organism.p28...
(for mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
, human
Human
Humans are the only living species in the Homo genus...
, and other species), fluorescent in situ hybridization (FISH
Fluorescent in situ hybridization
FISH is a cytogenetic technique developed by biomedical researchers in the early 1980s that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH uses fluorescent probes that bind to only those parts of the chromosome with which they show a high...
) mapping, transgenic insertion site mapping (G-to-FISH mapping) and clone labeling for FISH
Fluorescent in situ hybridization
FISH is a cytogenetic technique developed by biomedical researchers in the early 1980s that is used to detect and localize the presence or absence of specific DNA sequences on chromosomes. FISH uses fluorescent probes that bind to only those parts of the chromosome with which they show a high...
experiments. The Genome Resources components includes a clone repository (Mammalian Gene Collection (MGC) cDNA (mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
and human
Human
Humans are the only living species in the Homo genus...
), genomic clones including human bacterial artificial chromosome
Bacterial artificial chromosome
A bacterial artificial chromosome is a DNA construct, based on a functional fertility plasmid , used for transforming and cloning in bacteria, usually E. coli. F-plasmids play a crucial role because they contain partition genes that promote the even distribution of plasmids after bacterial cell...
s (BACs)) and provides project consultation and design assistance (annotation, database queries
Information retrieval
Information retrieval is the area of study concerned with searching for documents, for information within documents, and for metadata about documents, as well as that of searching structured storage, relational databases, and the World Wide Web...
, probe selection). It also provides cDNA library
CDNA library
A cDNA library is a combination of cloned cDNA fragments inserted into a collection of host cells, which together constitute some portion of the transcriptome of the organism. cDNA is produced from fully transcribed mRNA found in the nucleus and therefore contains only the expressed genes of an...
screening and quantitative PCR.
Genetic and Statistical Analysis
This Core Facility shares a manager (of the Genetic Analysis, or genotypingGenotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
component) with the DNA Sequencing and Synthesis facility. The Statistical Analysis component has its own dedicated manager.
The Genetic Analysis area includes all Illumina
Illumina (company)
Illumina, Inc. is a company incorporated in April 1998 that develops, manufactures and markets integrated systems for the analysis of genetic variation and biological function. Using its technologies, the company provides a line of products and services that serve the sequencing, genotyping and...
technologies, including genome-wide (Infinium) and custom content (iSelect and GoldenGate) genotyping
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
, methylation, microRNA, and gene expression
Gene expression
Gene expression is the process by which information from a gene is used in the synthesis of a functional gene product. These products are often proteins, but in non-protein coding genes such as ribosomal RNA , transfer RNA or small nuclear RNA genes, the product is a functional RNA...
microarrays
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
. It also performs capillary-based genotyping
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
(Applied Biosystems
Applied Biosystems
Applied Biosystems, Inc. started as GeneCo , was the name of a pioneer biotechnology company founded in 1981 in Foster City, California, in the San Francisco Bay Area...
Taqman
TaqMan
TaqMan probes are hydrolysis probes that are designed to increase the specificity of real-time PCR assays. The method was first reported in 1991 by researchers at Cetus Corporation, and the technology was subsequently developed by Roche Molecular Diagnostics for diagnostic assays and by Applied...
and SNaPshot, microsatellite
Microsatellite
Microsatellites, also known as Simple Sequence Repeats or short tandem repeats , are repeating sequences of 2-6 base pairs of DNA....
s), custom genotyping
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
(e.g. heteroduplex
Heteroduplex
A heteroduplex is a double-stranded molecule of nucleic acid originated through the genetic recombination of single complementary strands derived from different sources, such as from different homologous chromosomes or even from different organisms....
analysis), mouse
Mouse
A mouse is a small mammal belonging to the order of rodents. The best known mouse species is the common house mouse . It is also a popular pet. In some places, certain kinds of field mice are also common. This rodent is eaten by large birds such as hawks and eagles...
genotyping
Genotyping
Genotyping is the process of determining differences in the genetic make-up of an individual by examining the individual's DNA sequence using biological assays and comparing it to another individual's sequence or a reference sequence. It reveals the alleles an individual has inherited from their...
(for cross progeny and genetic linkage
Genetic linkage
Genetic linkage is the tendency of certain loci or alleles to be inherited together. Genetic loci that are physically close to one another on the same chromosome tend to stay together during meiosis, and are thus genetically linked.-Background:...
analysis), and methylation
Methylation
In the chemical sciences, methylation denotes the addition of a methyl group to a substrate or the substitution of an atom or group by a methyl group. Methylation is a form of alkylation with, to be specific, a methyl group, rather than a larger carbon chain, replacing a hydrogen atom...
analysis (for epigenetics
Epigenetics
In biology, and specifically genetics, epigenetics is the study of heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence – hence the name epi- -genetics...
research).
The Statistical Analysis component provides project consultation and power analysis
Statistical power
The power of a statistical test is the probability that the test will reject the null hypothesis when the null hypothesis is actually false . The power is in general a function of the possible distributions, often determined by a parameter, under the alternative hypothesis...
, statistical analysis (genetic
Genetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
, microarray
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
, and pathway data, epidemiology
Epidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
, population genetics
Population genetics
Population genetics is the study of allele frequency distribution and change under the influence of the four main evolutionary processes: natural selection, genetic drift, mutation and gene flow. It also takes into account the factors of recombination, population subdivision and population...
), and copy number variation analysis, as well as developing new statistical methods.
Biobanking
The Biobanking Core Facility has its own dedicated manager. It performs white cellWhite blood cell
White blood cells, or leukocytes , are cells of the immune system involved in defending the body against both infectious disease and foreign materials. Five different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a...
immortalization (from blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
) and banking, fibroblast
Fibroblast
A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen, the structural framework for animal tissues, and plays a critical role in wound healing...
culture
Cell culture
Cell culture is the complex process by which cells are grown under controlled conditions. In practice, the term "cell culture" has come to refer to the culturing of cells derived from singlecellular eukaryotes, especially animal cells. However, there are also cultures of plants, fungi and microbes,...
and banking, culture and banking of other cell types including non-human cells, genomic DNA
Nuclear DNA
Nuclear DNA, nuclear deoxyribonucleic acid , is DNA contained within a nucleus of eukaryotic organisms. In mammals and vertebrates, nuclear DNA encodes more of the genome than the mitochondrial DNA and is composed of information inherited from two parents, one male, and one female, rather than...
preparation from blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
, saliva
Saliva
Saliva , referred to in various contexts as spit, spittle, drivel, drool, or slobber, is the watery substance produced in the mouths of humans and most other animals. Saliva is a component of oral fluid. In mammals, saliva is produced in and secreted from the three pairs of major salivary glands,...
, tissues
Tissue (biology)
Tissue is a cellular organizational level intermediate between cells and a complete organism. A tissue is an ensemble of cells, not necessarily identical, but from the same origin, that together carry out a specific function. These are called tissues because of their identical functioning...
or cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, and whole-genome amplification (WGA).
Funding Sources
TCAG is funded by several agencies, including the Canada Foundation for InnovationCanada Foundation for Innovation
Created by the Government of Canada in 1997, the Canada Foundation for Innovation strives to build our nation’s capacity to undertake world-class research and technology development to benefit Canadians...
(CFI), Genome Canada through the Ontario Genomics Institute, the Ontario Ministry of Research and Innovation. 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.
Scientific Director
The Scientific Director of TCAG is Dr. Stephen W. SchererStephen W. Scherer
Stephen Wayne Steve Scherer, PhD, DSc, FRSC , is a Canadian scientist, whose research has revolutionized the understanding of genetic variation in human disease. He obtained his PhD at the University of Toronto under Professor Lap-chee Tsui, discoverer of the cystic fibrosis gene...
, Senior Staff Scientist in The Hospital for Sick Children's Research Institute, Director of the McLaughlin Centre, and a professor at the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
.
Scientific Management Committee
TCAG is governed by a Scientific Management Committee, who meet regularly to discuss high-level strategic planning. The Scientific Management Committee consists of:- Dr. Gary Bader
- Dr. Michael Brudno
- Dr. Jayne Danska
- Dr. Lisa Strug
- Dr. Andrew Paterson
- Dr. Peter Ray
- Dr. Shoshana Wodak
Drs. Bader and Brudno are located at the University of Toronto
University of Toronto
The University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
, and the others at The Hospital for Sick Children. The committee also includes three ex officio members: the Assistant Director, Facility Manager, and a representative from the Ontario Genomics Institute.
Associate Investigators
Since 2006, TCAG has appointed Associate Investigators. These associates consult on their specific areas of expertise, and assist in identification and implementation of new technologies. At present, there are six Associate Investigators: Drs. Esteban Parra (UTMUniversity of Toronto Mississauga
The University of Toronto Mississauga is a satellite campus of the University of Toronto, located in Mississauga, Ontario, Canada. The university is set upon a park-like campus on the valley of the Credit River, approximately 33 kilometres west of Downtown Toronto...
), Mary Shago (SickKids), Mark Silverberg (MSH
Mount Sinai Hospital (Toronto)
Mount Sinai Hospital is a hospital in Toronto, Ontario, Canada. Although it is physically linked by bridges and tunnels to two University Health Network hospitals , Mount Sinai is an independently operated facility...
), James Stavropoulos (SickKids), Michael Taylor (SickKids), and John Vincent (CAMH
Centre for Addiction and Mental Health
The Centre for Addiction and Mental Health is a consortium of mental health clinics at several sites in Toronto, Ontario, Canada. Its name in French is Centre de toxicomanie et de santé mentale...
).
Scientific Advisory Board
High-level scientific oversight of TCAG's scientific mandate and operations is provided through an external Scientific Advisory Board (SAB). The SAB members are:- Dr. Nigel Carter, PhD (Chair), Wellcome Trust Sanger Institute
- Dr. Abdallah S. DaarAbdallah DaarAbdallah Daar is Professor of Public Health Sciences and of Surgery at the University of Toronto, and Senior Scientist and Director of Ethics and Commercialization at the McLaughlin-Rotman Centre for Global Health, University Health Network and University of Toronto...
, University of TorontoUniversity of TorontoThe University of Toronto is a public research university in Toronto, Ontario, Canada, situated on the grounds that surround Queen's Park. It was founded by royal charter in 1827 as King's College, the first institution of higher learning in Upper Canada...
Joint Centre for Bioethics - Dr. Mark Daly, Whitehead InstituteWhitehead InstituteFounded in 1982, the Whitehead Institute for Biomedical Research is a non-profit research and teaching institution located in Cambridge, Massachusetts, USA....
- Dr. Samuel Levy, Scripps Research Institute
- Dr. Arend Sidow, Stanford UniversityStanford UniversityThe Leland Stanford Junior University, commonly referred to as Stanford University or Stanford, is a private research university on an campus located near Palo Alto, California. It is situated in the northwestern Santa Clara Valley on the San Francisco Peninsula, approximately northwest of San...
The Ontario Genomics Institute (OGI) and Genome Canada also provide ex officio members.