The Genome Research Centre (GRC) is an university initiative created to place Hong Kong at the forefront of genomics research. The GRC focuses on establishing key core facilities and the development of multidisciplinary research programs to combine leading-edge research in molecular and cell biology, biochemistry, bioinformatics, and clinical medicine.
DNA sequencing and other technologies for probing DNA constitute a foundation for genomics research at the GRC. Infrastructure and genotyping expertise stemming from our participation in The International HapMap Project is contributing to a large number of multidisciplinary collaborative projects focusing on the use of candidate gene and genome-wide association studies to identify genetic loci contributing to complex diseases such as cancer, osteoporosis, schizophrenia, diabetes, lumbar disc degeneration, and Alzheimer’s disease.
The new generation of massively parallel DNA sequencers represents a paradigm changing technology. Key collaborative proof-of-principle projects make use of the Solexa and other platforms to drive technology development in areas such as de novo sequencing, transcriptomics, and epigenomics to encourage HK medical investigators to use the new tools to address their areas of biology interests.
Collaborative GRC Genomics Research Projects
(with Professor Si Lok's research team)
Next Generation DNA Sequencing
De novo DNA Sequencing
GRC scientists are engaged in collaborative projects to develop the technology to sequence and to assemble a variety of complex small and large genomes using short Solexa-type reads.
The GRC wish to encourage HK investigators to use DNA sequencing to characterize the transcriptomes in their biological areas of interest. As a part of an AoE program and in collaboration with the Department of Microbiology, new generation DNA sequencing is used to characterize and to quantify levels of host and viral derived mRNA, miRNA and alteration in RNA processing in influenza virus infected human macrophage. This work aims to understand the regulatory network and the trigger leading to pathogenesis. Another area of active investigation is the characterization of the cancer transcriptome, especially the microRNAome that could provide insight to the disease and the identification of useful biomarkers.
The project is a part of the AoE program on Influenza Virus and calls for the eventual sequencing of a large number of virus isolates and quasi-species in an effort to correlate pathogenicity with genotype. The data would also enable taxonomic assessment of viral evolution, transmission patterns and the development of emerging strains and viral quasi species in the evasion of host defense and drug treatment.
Another area of investigation is metagenomics, where DNA sequencing is used to characterize the complex relationships within medical and environmental microbial communities.
Medical Resequencing, SNP discovery and Structural-Genomics
Genome-wide targeted gene resequencing is used to identify nucleotide alterations in disease models to identify and to catalog rare single nucleotide polymorphic makers to elucidate the genetic mechanisms of common diseases. The GRC has also developed new high throughput method to detect fine-structural variations (copy number alterations, inversion, translocations) at high resolution. The first phase of the work is to catalog extent of genomic variations in man followed by studies to correlate "structural genotype" to phenotype leading to the identification of new diagnostics and drug targets.
Genome-wide Association Studies (GWAS)
(GRC Scientists: Professor Pak Sham, Dr Stacey Cherny)
GRC scientists are involved in several GWAS of common and rare diseases, as well as of quantitative variation. These projects include both collaborations with other PIs as well as projects headed by GRC scientists. The projects are in various stages of completion, with one on Hirschsprung's Disease the first to be completed, resulting in the identification of a single-base variant in NRG1 as a novel predisposing risk factor (Garcia-Barcelo et al 2009). Other GWAS include:
Where possible, a strategy of using a common pool of genotyped controls is used. Depending on the application, genotyping has involved the use of the Affymetrix Genome-wide SNP array 6.0, the Illumina Human 610-Quad BeadChip Array, which assays over 550,000 SNPs and an additional 60,000 CNV-specific probes, and the Sequenom MassARRAY platform.