Getting Involved

There is an urgent need for predictive biomarkers associated with disease development, associated co-morbidities and response to treatment. Delayed diagnoses of cancer and other non-communicable diseases (NCDs), resulting in high-risk subtypes underpinned by a varying degree of gene-environment interaction, supports a responsive study design relevant to the specific case scenario.

Phase 1 of our pathology-supported genetic testing (PSGT) approach is focused on the identification of pathogenic mutations in high-penetrance genes, which may also serve as treatment targets where appropriate (e.g. PARP inhibitors in ER/PR/HER2- / triple-negative BRCA1/2 mutation carriers with metastatic breast/ovarian cancer).

In Phase 2 of PSGT the results of commercially-available assays such as MammaPrint/BluePrint or OncoDEEP, combining microarray or next generation sequencing of tumour DNA with immunohistochemistry for determination of protein expression, are evaluated to identify the relevant gene profile or drug target/s for optimal therapy of cancer subtypes.

Based on the outcome of 1 and 2, we may proceed to Phase 3 of PSGT, involving a questionnaire-based assessment to determine eligibility and facilitate interpretation of whole exome sequencing (WES).  WES combined with long-range Minion nanopore sequencing may be used to help distinguish between inherited and lifestyle-related forms of NCD’s, which require different treatment strategies. Questions raised at each step of PSGT are discussed at a monthly Clinical Genomics Forum, in the context of lessons learned on a case by case basis to improve patient care.


Monthly case discussions are based on unanswered questions raised by OncoDNA/Oncomine, BRCA/Invitae, MammaPrint/BluePrint, etc. test reports that in turn provide valuable insight for introduction of a mixed methods study design into student training and clinician education.  Questions asked when unexpected genetic results are obtained, translates into a better understanding of clinical dilemmas that can be addressed responsively by combining qualitative analysis (using a case study approach) with a quantitative research component. This involves extended laboratory testing using whole exome or long-range nanopore sequencing, coupled with data mining using sophisticated online tools.

In this context, bone health was studied in postmenopausal breast cancer patients treated by surgeon and charity runner, Dr Karin Baatjes. Her research led to the development of a three-pronged clinical management approach, incorporating whole exome sequencing (WES). With this pathology-supported genetic testing approach moderate- to high-risk genes, as well as low-penetrance variants in key disease pathways shared by many non-communicable diseases (NCDs), could be assessed simultaneously for clinical relevance to: 1) familial risk, 2) modifiable lifestyle and environmental triggers, and 3) treatment failure or therapy-induced co-morbidities.


Autism, epigenetics, pharmacogenetics, iron dysregulation, medical aid reimbursement policy and ethical issues were among the topics discussed at the 10th Applied Genetics Workshop. This event took place from 30-31 October 2015 with a special focus on the need for a “Learning Healthcare System”.

So much has been accomplished over the last decade that helped us to move from single-gene analysis to microarrays and next generation/exome sequencing! One of the highlights was the registration of the workshop as a Short Course at Stellenbosch University entitled “Clinician Training in Pathology-Supported Genetic Testing to be Applicable to the Benefit of Society”. This was done according to the requirements of the South African National Qualifications Framework (NQF). The content focused on life-long learning was approved at NQF level 8. This relates to a scope of knowledge that engages the learner in an area at the forefront of clinical practice. Understanding the methodologies and techniques relevant to genomics and how to apply such knowledge in a clinical context are necessary for effective research translation.

It is important to critically review genetic information in specialised contexts in order to develop creative responses to ethical issues and obstacles in the path to personalised medicine.

An expert panel has been selected to participate in a series of lectures forming part of a UK-South Africa Researcher Links Grant awarded to Prof Maritha Kotze. This will focus on the appropriate incorporation of genomics in routine clinical and dietetic practice.

10th Applied Genetics Workshop:
30 October 2015 from 8h30-16h00

Strategic Planning & Lecture Session 1
: 31 October 2015 from 9h00-13h00

Faculty of Medicine and Health Sciences, Teaching Block, Lecture Room 11, Francie van Zijl Drive, Stellenbosch University, Tygerberg, CAPE TOWN


9h00: Welcome and Introduction – Prof Nico Gey van Pittius, Deputy Dean: Research Faculty of Medicine and Health Sciences, Stellenbosch University

9h30: A combined service and research approach: Maximising beneficence in the application of personalised medicine – Dr Tyson Welzel, Vice Chair, Stellenbosch University Health Research Ethics Committee; Nicola Barsdorf,
Head of Health Research Ethics, Stellenbosch University

10h15: Epigenetics and the prospect of personalised interventions in the fight against non-communicable diseases –
Dr Stuart Raleigh, Head of the Centre for Physical activity and Chronic Disease, University of Northampton, UK


11h30: Chromosomal microarray (CytoScan): Genomic diagnostics for patients with intellectual disability and autism – Dr Mike Urban, Head of the Clinical Unit, Clinical Genetics and Genetic Counselling, Stellenbosch University and Tygerberg Hospital

12h00: RNA microarray (MammaPrint): Impact on clinical decision-making in South African patients with early stage breast cancer – Dr Heinrich Pohl, Department of Surgery, Stellenbosch University and Tygerberg Hospita.

12h30: Application of targeted next-generation sequencing (OncoDEEP) and microarray tumour profiling in clinical practice- Dr Ettienne Myburgh, Department of Surgery, Stellenbosch University and Panorama Medi-Clinic

LUNCH: 13h00

13h30: Molecular oncology for clinicians – Dr Johann Riedemann, Medical Officer, Karl Bremer Hospital (PhD in Molecular Oncology, University of Oxford, UK)

14h00: Iron in the brain: Not too much and not too little – Dr Ronald van Toorn, Department of Paediatrics and Child Health, Stellenbosch University and Tygerberg Hospital.

14h30: Whole exome sequencing in iron-deficient patients diagnosed with multiple sclerosis – Prof Susan J van Rensburg, Department of Pathology, Stellenbosch University.

15h00: Molecular genetics and medical schemes: Where to? – Prof Manie de Klerk, General Manager, Metropolitan Health Risk Management

15h45: Closing remarks: Providing a genomics database resource for clinical interpretation Prof Maritha Kotze, Department of Pathology, Stellenbosch University and Gknowmix

Saturday 31 October 2015 9h00-13h00

All stakeholders are invited to form part of a Working Group to be established for the UK-South Africa Researcher Links Initiative approved for funding by the National Research Foundation from October 2015 to March 2016. The first meeting will be in Cape Town immediately after the workshop (31/10/2015), followed by a series of lectures in different regions of South Africa (program to be finalised).

At this first meeting problems related to the incorporation of genomics in clinical practice will be presented by Dr Ettienne Myburgh, who performed an external audit of the Gknowmix database generated at the interface between the laboratory and clinic. Dr Helen Muir and PhD student Nicole van der Merwe will present case studies and the challenges faced as we move from traditional single- to multi-gene testing and next generation/exome sequencing.Based on the use of an ethics approved protocol showing how research influences clinical practice and vice versa, the need for of a “learning healthcare system” will be explored and motivated by Prof Maritha Kotze. Dr Hilmar Lückhoff will explain how evidence generated from the central genomics database is used to design testing algorithms for conditional approval and reimbursement by participating medical schemes in South Africa.
Dr Stuart Raleigh will evaluate the potential benefits and risks of pathology-supported genetic testing and formulate a strategy for possible introduction of genetic screening tests using a similar process in the UK. Joint health outcome studies related to his field of expertise including Sport Medicine will allow for adjustments to be made over time, resulting in continual improvement of genetic testing across the disease spectrum.

An expert panel will be nominated to participate in the above-mentioned lecture series focused on the incorporation of genomics in routine clinical and dietetic practice. Proposals for topics are invited in the form of peer-reviewed research articles published or accepted for publication during the evaluation period. The best idea for research translation with high potential impact on patient care was awarded a prize of R20 000: Dr Rispah Torrorey-Sawe of Kenya.


The 2012 GeneTalk Workshop was a great success with nearly 100 healthcare professionals attending. Thanks to all the speakers and panel members for playing such an important part in the clear message that was conveyed about the benefits of pathology supported genetic testing (PSGT). We are so proud of our students Kathy Grant and Kobus Pretorius who presented the results of their research in such a way that everyone could see they know what they are talking about. Their hard work will certainly not be “lost in translation” as Mardelle Schoeman pointed out in her ethics talk which was really outstanding.

Dr Junaid Gamaldien’s talk was spectacular. There is no better way to describe the way he explained the application of clinical whole genome/exome sequencing. Prof Susan van Rensburg furthermore clearly explained the importance of high homocysteine levels so everyone who attended can now understand the serious implications of a disturbance in the methylation pathway.

Everyone enjoyed listening to Dr Paul de Flamingh and it was clear that no matter how well we try to explain the test results in the report – the importance of a knowledgeable healthcare professional taking care of the implementation of the results is vital to ensure a meaningful genetic testing experience. And depending on the test outcome post-test feedback may need to be stretched out over several consultations. In future we will select at least 1-2 such case studies for presentation by different doctors at our workshops.

There is a lot of excitement around the Sport Injury Genescreen presented in a highly professional way by Prof Malcolm Collins. A very high standard was set and when he said that the test must be made available sooner rather than later it was well accepted. If anyone who attended the talk have any suggestions for him and Dr Alison September of UCT – while coding of the test information into the Gknowmix system is being finalised over the next few weeks – please let us know. Alison helped Kobus with his talk that received so many compliments because genetics could now be understood for the first time by several of the attendants. Prof Johann Schneider very elegantly presented the Pathology Supported Genetic Testing concept which he supported from the start and set the stage for an memorable event.

Dr Martin de Villiers provided a funder’s perspective of personalised medicine, noting that oncology has paved the way. Hopefully genetic testing for other chronic / non-communicable diseases will follow soon. Prof Manie de Klerk invited us during the last session to discuss the proposal he prepared in this respect for medical aids. It can be expected that this will follow the same route as payment for MammaPrint that he got approved in 2009!

The last talk by Dr Frans Cronje was the cherry on the cake! He defined three indicators for considering genetic testing: family history, abnormal pathology / biochemistry tests and when certain drugs are being prescribed. It will now be much simpler for doctors to decide whether to refer a patient for a test or genetic counselling. One of the GPs who attended suggested that the GRACE Foundation (Genomic Research Advancing Clinical Excellence) should be established as an outcome of this workshop and we will certainly look into this possibility. BY PROF MARITHA KOTZE – my presentation that followed after the explanation of Prof Schneider what PSGT is about can be accessed at YouTube.


“Dear Maritha – When you joined us a few years ago, I never expected that the venture would be so successful in such little time! You did a superb job under often challenging circumstances. The wide recognition and support that you enjoy from clinicians, scientists, geneticists, genetic counsellors, health funding authorities and researchers from the public and private sectors respectively, confirm that you are a leading role-player in the establishment of a new era in modern health science in our beloved country. The growing number of internationally acclaimed research publications, the expansion of research projects, the increasing number of postgraduate students (M and PhD) and the successful attraction of research funding clearly demonstrate that the integration of genetics, pathology and clinical medicine is indeed a successful strategy to promote clinical care of patients, training and translational research. The successful workshop on Friday was another highlight, and I express my appreciation and congratulations to your and all the speakers for an excellent programme. Thank you very much indeed.” FROM PROF JOHANN SCHNEIDER (Speaker – Head of the Dept of Patholgy, University of Stellenbosch)

“I am very proud and at the same time humbled to have been part of this year’s GeneTalk. The number of participants and the quality of the talks that I was able to see (can’t wait to see the DVD) was inspirational and invigorating – I am amped! As a community, we have a real opportunity to become leaders in this burgeoning new era of clinical genomics – instead of being part of the “let’s wait and see crowd”. Thanks Gknowmix and especially Maritha for the opportunity.” BY DR JUNAID GAMALDIEN (Speaker – Bioinformaticist, University of the Western Cape)

“It was a huge pleasure to be part of this great day. I hope my little contribution helped to illustrate the value that PSGT will bring to clinical medicine. I also have to congratulate you on a well designed as well as executed academic meeting! Even I as a plain clinical person could follow most of the presentations! The DVD will help to refresh and digest more of the rest!! I would like to say again that I truly believe that the face of medicine is going to change dramatically in the next decade or so. We are going to move away from the out-dated format of curative medicine to preventative medicine with genetics and stem cell technology playing major roles. Apart from any other considerations the plain economics of delivering medical services to all people makes this a no-brainer (as the young people like to say)! Once again, congratulations! I will keep you posted on the progress of my patient presented as a case study”. BY DR PAUL DE FLAMINGH (Speaker – Private Practicing Gynaecologist)

“It was indeed a great success and you have been hugely gracious in giving us all the credit. I am sure all will agree that your vision, focus, extremely hard work and total belief in PSGT is the catalyst and drive behind the sure and steady growth of this new paradigm in medicine – one that will definitely bring about the “personalised medicine” dream that was hoped for when Collins and Venter cracked the genome. So on behalf of us all a big THANK YOU Maritha.” FROM PROF TONY BUNN (Speaker – Head of the Innovation Centre, South African Medical Research Council).

“I agree with everything Tony has said! It is your vision and passion from the days of GeneCare already that has always inspired me..thank you for always being so passionate about everything you do. It is going to be great working with you. I am looking forward to the year ahead.” FROM DR ALISON SEPTEMBER (Co-Speaker – Exercise Science and Sports Medicine Institute, Medical Research Council and University of Cape Town)

“Thank you for the e-mail and great summary of presenters/presentations of Friday’s hugely successful workshop. Your vision – your leadership – and passion for what you are doing is so unique and a rare combination seldom found amongst scientists. Your unbelievable work ethic and ‘never ever give up attitude’ is a lesson to us all. Thank you for leading – (we are glad to follow!) – as we know the way you are heading is the future. The 25th October 2013 is diarized!” FROM DR HEIN BADENHORT (Expert Panel Member – Private Practicing Medical Doctor, Gauteng)

“Very well done on an excellent meeting. They get better every year. You deserved all the accolades you and your students got yesterday. If any GP’s would like to chat to me if they are not sure about using Gknowmix in their practices, I am available to help with the clinical side of things.” FROM DR HELEN MUIR (Expert Panel Member – Private Practicing Medical Doctor, Cape Town)“

Congratulations on a very informative workshop! We all know a lot more now!” FROM DR LOUISE LINDENBERG (Delegate – Private Practicing Medical Doctor, Cape Town)

“I would also like to congratulate you on a very successful workshop. I think you can be very satisfied and proud! Once the dust has settled, I would like to discuss your Familial Hypercholesterolaemia work and how you think one can take it forward and perhaps also what role we could play in this. As a clinical genetics group, we feel this is something that should be a priority, as there must be so many people out there with FH who are unaware that they have the condition. We feel that you are probably the person with the most insight into why this is the case and we would therefore like to talk to you about how we could approach the situation” FROM MARDELLE SCHOEMAN (Speaker – Genetic Counsellor, University of Stellenbosch and Tygerberg Hospital, Cape Town).

“Thank you so much for your tireless efforts and input in the field of genetics. Your passion and enthusiasm is contagious! I feel so blessed that our paths have crossed, your generous heart for people and God given desire to help them is making such a powerful impact in developing genetic research and clinical tools. It is an honour to learn from you and discover new ways of guiding clients with preventative health care and appropriate treatment of gene-related conditions. Gknowmix’s approach of adding biochemistry as well as diet and lifestyle information to the genetic interpretation (of the wellness screen) is very useful, especially in clients who are already presenting with lifestyle disease. Thank you for a great conference, I look forward to grow in knowledge with you and your team in this fascinating field to truly change the face of the health profession of the future, to be preventative patient focussed health-care.” FROM DALENE ROTTIER-WILSON (Delegate – Private Practicing Registered Dietician, Pretoria & Johannesburg)

“Congratulations on the successful day we had on Friday! I think Prof Schneider said it beautifully in his email – you really are such an asset to the university and of course to us, your students. There is no stopping the genetic wave! It’s the way medicine is going, everyone there was saying it. I’ve followed the e-mails about the misunderstanding about MammaPrint – I thought the slides were clear but it shows how easily things can be lost in translation!! We are experiencing a lot of interest in the test and it is important to get the correct information out there.” FROM KATHLEEN GRANT (Speaker – PhD student, Cape Peninsula University of Technology).

“The workshop on Friday was a huge success. Thank you for the hard work and enthusiasm. It is an inspiration to all of us. You deserve all the compliments. It is wonderful that after many years of hard work you are acknowledged for this. You are really an example to all of us. I would like to become involved with any Gkwnmix project or patient where you may need a dietician. It is fantastic work that you do.” FROM
DAVONNE OLIVIER (Delegate – Private Practicing Registered Dietician).

Speakers at GeneTalk

Genetalk 26 Oct 2011

Students with Professor Maritha Kotze and co-supervisor Dieter Geiger