Scientists In Singapore Make Important Meningococcal Disease Breakthrough
Genome Institute of Singapore scientists identify important genetic variants that confer susceptibility to Meningococcal Disease, through the largest ever study of it’s kind involving more than 1000 subjects.
Scientists at the Genome Institute of Singapore (GIS), a biomedical research institute of the Agency for Science, Technology and Research (A*STAR), recently collaborated with colleagues from the UK, The Netherlands, Austria and Spain in a genome wide association study and two replication studies which help to identify important genetic variants that confer susceptibility to Meningococcal disease (MD).
These studies involved 1,443 MD patients, the largest cohort of MD patients who have participated in similar studies reported to date. The knowledge gained will help further research towards the development of vaccines for MD.
The set of studies provide the first completely convincing evidence that susceptibility to MD, like malaria, is due, at least in part, to human genetic variation.
Although the susceptibility of human genes to infectious disease has been well established through the identification of mutations that protect against malaria, this has only recently been accepted for a wider variety of infections.
Led by GIS Senior Research Scientist Dr Sonia Davila, GIS Senior Group Leader and Associate Director for Infectious Diseases Dr Martin Hibberd and Prof Michael Levin, Professor of Paediatrics and International Child Health at Imperial College London, the finding was published in Nature Genetics on 8 August, 2010.
It was found through the studies that a cluster of polymorphisms within two genes belonging to the complement factor family, CFH and CFHR3, was shown to have an association with MD in the three analysed cohorts.
“CFH is well known in MD because it is hijacked by the N.meningitidis bacteria to protect it from complement mediated killing and because the prevention of this interaction has been a breakthrough in a new vaccine being developed against group B N.meningitidis.” said Dr Sonia Davila. “Our study suggests that the host genetic variation in these regulators of complement activation plays a role in determining invasive disease versus asymptomatic colonization by the bacteria, which could have implications for both vaccine development and potential new therapies.”
Dr Martin Hibberd added, “Although vaccination has reduced the incidence of sero-group C MD in some countries, there is currently no generally effective vaccine for sero-group B MD which remains an important problem in many developed countries. Our work confirms CFH as a possible vaccine target and should improve future strategies to prevent sero-group B disease.”
“It has been appreciated for some time that there is a genetic contribution to susceptibility to MD, as all individuals carry the organism harmlessly in their nose and throat, but only a minority become unwell,” said Associate Professor David Burgner from the Murdoch Childrens Research Institute, Royal Children’s Hospital, Parkville, Victoria, Australia. “This is an exciting and important study that looked for important genetic factors that influence susceptibility across the whole human genome. To achieve this, they brought together meningococcal researchers from various countries, which is crucial in performing genetic studies of relatively rare but important diseases. This genome-wide approach has been used successfully in chronic adult diseases, such as diabetes, but it has only recently been applied to infectious diseases, which are the leading cause of death and severe illness in childhood.”
Professor Michael Levin, who led the study with Prof Hibberd at GIS said: “This study represents the culmination of a 15-year collaborative international effort to identify genes which determine why some individuals develop this lethal infection, whereas the majority of the population carry the bacteria without ever becoming ill. The results of our study provide definitive evidence that genetic variations in the Factor H and Factor H related proteins are important determinants of susceptibility to the disease. The findings are an important breakthrough in our understanding of this infection and will be important in development of effective vaccines.”
He added, “The success of this study highlights the importance of international collaboration and could not have been achieved without the thousands of affected patients and controls agreeing to include their DNA in this analysis.”
The authors contributed equally to this work:
- Infectious Diseases, Genome Institute of Singapore, Singapore
- Division of Infectious Diseases, Department of Medicine, Imperial College London, UK
- Research Computing, Genome Institute of Singapore, Singapore
- Department of General Pediatrics, Medical University of Graz, Graz, Austria
- Division of Pediatric Hematology, Immunology and Infectious diseases, Emma Children’s Hospital Academic Medical Center, The Netherlands
- Institute of Child Health, University of Liverpool, Alder Hey Children’s NHS Foundation Trust, Liverpool, UK
- Department of Pediatrics, Radboud University Nijmegen Medical Centre, The Netherlands
- Department of Pediatrics, Erasmus MC-Sophia Children’s Hospital, University Medical Center, Rotterdam, The Netherlands
- Department of Immunology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
- Pediatric Emergency and Critical Care Division, Department of Pediatrics, Hospital Clínico Universitario de Santiago, Santiago de Compostela, Spain
- Grupo Gallego de Genética, Vacunas e Investigación Pediátrica, Instituto de Investigación Sanitaria de Santiago, Galicia, Spain
- Unidade de Xenética, Departamento de Anatomía Patolóxica e Ciencias Forenses Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain
- Instituto de Medicina Legal, Facultade de Medicina, Universidade de Santiago de Compostela, Santiago de Compostela, Galicia, Spain,
- Members of the consortium are listed in a Supplementary Note
About the Genome Institute of Singapore
The Genome Institute of Singapore (GIS) is an institute of the Agency for Science, Technology and Research (A*STAR). It has a global vision that seeks to use genomic sciences to improve public health and public prosperity. Established in 2001 as a centre for genomic discovery, the GIS will pursue the integration of technology, genetics and biology towards the goal of individualized medicine. The key research areas at the GIS include Systems Biology, Stem Cell & Developmental Biology, Cancer Biology & Pharmacology, Human Genetics, Infectious Diseases, Genomic Technologies, and Computational & Mathematical Biology. The genomics infrastructure at the GIS is utilized to train new scientific talent, to function as a bridge for academic and industrial research, and to explore scientific questions of high impact.
About the Agency for Science, Technology and Research (A*STAR)
The Agency for Science, Technology and Research (A*STAR) is the lead agency for fostering world-class scientific research and talent for a vibrant knowledge-based and innovation-driven Singapore. A*STAR oversees 14 biomedical sciences, and physical sciences and engineering research institutes, and seven consortia & centres, which are located in Biopolis and Fusionopolis, as well as their immediate vicinity.
A*STAR supports Singapore’s key economic clusters by providing intellectual, human and industrial capital to its partners in industry. It also supports extramural research in the universities, hospitals, research centres, and with other local and international partners.
Topics: 2010, A*Star, Agency for Science, Asia, biomedical, children, genome, Genome Institute of Singapore, GIS, Governance, government, health care, Health Care, human genes, human genetic variation, infections, infectious diseases, Malaria, MD, Meningococcal Disease, moniter, monitor, news, Pacific, Singapore, society, suscepibility, Technology and Research, vaccine
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