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July 2011


Predigree Tree

The GRC is pleased to announce the successful completion of a major study making use of exome sequencing to identify de novo mutations in family trios and represents the first use and execution of targeted DNA sequencing at HKU. De novo mutations as observed in this study may in part explains the high worldwide incidence of schizophrenia. This work is published in Nature Genetics and is an International Collaboration between investigators in France (INSERM), Canada (University of Montreal, Centre Hospitalier Universitaire Sainte-Justine Research Centre) and the GRC. The GRC was a major site for exome DNA sequencing and the bioinformatics that led to the identification of candidate genes, most of which have not been previously linked to schizophrenia.




June 2011


A lesson learnt from the Severe Acute Respiratory Syndrome (SARS) crisis, the GRC has a contingency plan to respond rapidly to infectious agents. This plan was tripped in the recent epidemic outbreak of Scarlet Fever in Hong Kong. The GRC in collaboration with the Kwok-Yung Yuen’s group at the Department of Microbiology sequenced the genomes of two blood culture isolates of Group A Streptococcus pyogenes from a fatal invasive streptococcal infection and toxic scarlet fever case in Hong Kong. Making use of the powerful 454- and Illumina sequencing platforms and the bioinformatics capabilities at the GRC, a high-resolution draft genome sequence was obtained in less than three days and the ensuring sequence-based diagnostic tests for this organism were in clinical use a few days later.

Data DiagramThe genome of the epidemic strain is closely related to that of the widely distributed M12 serotype, but having two major and unique insertions containing antibiotic resistance genes and other determinants that are believed to be responsible for the increased virulence. Sequences in these unique newly identified segments provide strain-specific assays to diagnose and monitor the prevalence of this epidemic strain in Hong Kong and Southern Asia. Work is continuing to elucidate the mechanisms of pathogenesis from the genomic information.



May 2011


The GRC in collaboration with Tong Zhang (Environmental Biotechnology Laboratory, HKU) has completed the first of a series of metagenomics studies to characterize the composition and changing dynamics of microbial communities in wastewater treatment plants by the use of high throughput 454-pyrosequencing. This work appeared in the journal Water Research and it exemplified GRC’s continuing efforts to promote use of the latest genomics tools in the nonmedical disciplines.Sewage Study


April 2011


Patent DiagramThe GRC was granted US patent 7,932,029 on methods for nucleic acid mapping and identification of structural-variations in nucleic acids. One embodiment provides methods to produce very precise long-paired end reads of up to 50-kb or more separation distance that can be sequenced on the new generation DNA sequencers to identify large scale structural variations such as insertions, deletions, inversions or translocations. The ability to study these variations at 50-kb resolution would allow access to the 1-5% of the genome that is current not well studied. Another embodiment, the invention is used to create high-resolution genomic scaffolds for de novo genomic assembly.

It is becoming clear that structural variations account for far greater diversity between individuals than the single nucleotide polymorphisms (SNPs) and is likely to play a role in disease. Whole genome de novo assembly to identify these types of variations (doi:10.1038/nbt.1904) is time consuming and costly. The ability to produce paired-end reads of large and precise separation provides a mean for rapid and low cost surveys of genomes for such variations. Commercial development of this technology is in progress.




March 2011


The GRC and Pak Leung Ho of the Department of Microbiology reported the complete sequence of pNDM-HK encoding NDM-1 carbpenemase from the first of such multidrug-resistant Escherichia coli strain isolated in Hong Kong.

Plasmid MapPublic health authorities have expressed serious concerns with the potential spread of novel drug resistance gene, NDM-1 (New Delhi metallo-beta-lactamase). The so termed “super bugs” harboring this gene was reported in the popular press to have been brought to Europe last year from the Indian subcontinent through medical tourism. Since the therapeutic options for infections by these organisms are very limited, the complete sequence of pNDM-HK was a necessary first step to understand the mechanisms for emergence and the potential horizontal spread in Hong Kong. This work is reported in PLoS One.