Outline of research
A major aspect of the Unit's agenda is the identification of genes underlying disease in South African populations. With the recognition that there is limited national capacity for high-throughput genotyping and sequencing technology, the Genomic Platform, for high-throughput genetic analysis has increased the workload within the Unit while offering spare capacity to other researchers in the Faculty of Health Sciences at UCT and the Western Cape. The improved infrastructure within the MRC Unit has been essential to realise our mission of increased capacity development.
Since its inception in 1990, the Retinal Degenerative Disorders (RDD) screening programme at the Division of Human Genetics has made several advances in retinal research. In collaboration with Retina South Africa (Retina SA), the RDD registry/database has grown to contain 1250 families with DNA archived from 2990 individuals. Currently, the registry has clinical and genetic change (mutation) data on a wide range of patients who are affected with a range of RDDs including Stargardt disease, dominant, recessive and X-linked forms of Retinitis Pigmentosa, macular degeneration, Usher syndrome and Leber Congenital Amaurosis, amongst others. To date, RDD research at UCT, which is largely supported by Retina SA and other funders such as the Medical Research Council, has led to several advances in the identification of genetic causes of RDDs. For instance, new retinal disease genes RP17 (CAIV) and RP13 (PRPF8) have been identified. These genes were originally mapped uniquely to South African families.
More recently, the UCT research team, together with Retina SA, has been involved in the Estonia screening project, in which patient samples are sent for testing on the Asper Microarray Chips. These chips contain all known mutations and variations in a wide range of RDDs for which patient DNA samples are tested. Currently, 15% of families in the database have been fully characterised in terms of disease-causing mutations. The fact that genetic changes underlying RDD in South Africa are unique compared to other international study sites presents a challenge in our attempts to characterise families in the registry. Nonetheless, this has only served to drive our research to new heights. The UCT RDD research team is constantly researching newly identified mutations as well as new screening methods that may enable detection of underlying mutations in inherited RDDs.
In keeping with the objectives of the RDD screening programme, genetic information is given to patients and their families through Genetic Counsellors who contact the patients directly. At the moment, 234 individuals in our registry have received results from our genetic screening. Information from the RDD research programme is published in scientific and medical journals; there have been 46 publications by the group in both local and international journals.
The Colorectal Cancer Research Consortium (CCRC), based in the Division of Human Genetics, was first established in 1999. This research focuses on assessment of the genetic basis of colorectal cancer (CRC), investigation of the sequence of molecular genetic changes that lead from neoplasm to malignancy in CRC as well as histopathology of CRC. To date a total of 1466 individuals from 409 families have been recruited onto the project. Our investigations have contributed towards the hypothesis that a significant proportion of colorectal cancers along the West Coast of South Africa, in individuals under the age of 45 years of age, is due to a number of identifiable germline genetic defects. Genetic changes, causative of disease, have been detected in more than 30 families. This has led to an internationally recognized program which delivers a genetic and clinical surveillance program to communities in the rural North West part of South Africa, with an effective reduction in both mortality and morbidity over more than 20 years. The program which won the Vice Chancellors Alan Pifer Award, also attracted an international clinical trial of simple aspirin, which has shown a significant level of effectiveness (in press: Lancet: Burn et al, 2011).
The Bipolar research project, based in the Division of Human Genetics was first approved in 1996. The focus was on the molecular basis of Bipolar Disorder. To date, a total of 919 individuals from 221 families have been recruited from all over South Africa.
A significant number of publications attest to the multidimensional analyses including neuropsychological profiling, imaging and functional genomics. From the genetics angle, our current work in this regard involves whole exome sequencing and whole genome sequencing.
One of the aims of the Division is to establish a strong research pedigree in pharmacogenetics/ pharmacogenomics. Pharmacogenomics research is aimed at investigating the role of inherited characteristics in differential susceptibility to disease as well as response to commonly used medication. Our aim is to identify genes that predispose individuals to high risk of disease or poor response to treatment. The diseases of interest include cancer, schizophrenia, HIV/AIDS, TB and diabetes neuropathy. We would also like to identify marker of susceptibility to cancer using human cancer cell lines as model systems.
Forensic Genetic Research
The Division of Human Genetics offered a 2-week Bsc (Med) Hons lecture module in Forensic Genetics for the first time in 2011. This module covered topics such as DNA markers, interpreting DNA profiles, Mitochondrial DNA analysis, Y chromosome markers, the legal system in South Africa, provision of expert evidence in court, and Forensic Report writing, amongst others. Two Honours research projects with a forensic genetic basis were also offered for the first time this year. Due to the success of these initial projects it is likely that more Human Genetic projects of a forensic nature will be offered in 2012.
Other active research projects:
- Neurodegenerative Disorders
- Muscular Dystrophy
- X-Linked Mental Retardation
Genetic research in the Unit is preceded by a history of good genetic practice of some 35 years in a well-established and functioning clinical, cyto and molecular genetics environment. Included in this programme of research is the unremitting clinical interest in the subject, family and community; tied to this is the commitment to providing follow up information to subjects on the ongoing research and potential benefits emanating from research. The Unit (and the Division of Human Genetics) has a historical and professional relationship with the South African Inherited Diseases Association (SAIDA) and several of its individual affiliates. Information for dissemination to support groups is developed with such organisations in order to be optimally informative and effective. Part of the employment condition of all students and staff is familiarisation with protocols to engage effectively with support groups, the public and range of media. Membership of steering committees and the national management committee of lay support organisations (such as Retina South Africa) have proven valuable in aligning our research with the needs of sufferers.
- Retina South Africa
- European Union
- The Drakenstein Child Lung Health Study ( Bill and Melinda Gates Foundation)