Understanding Genomics

7 min read

“How many of you want a career in genomics?” The question hung in the air as the auditorium filled with silence, albeit with a few chuckles. However, as the session unfolded, the students found themselves captivated by the possibilities that genomics offered.

To mark the 70th anniversary of the discovery of the DNA double helix, Precision Health Research, Singapore (PRECISE) co-hosted the “Understanding Genomics” forum in collaboration with the Science Centre Singapore, to enlighten the younger generation about the pivotal role genomics plays in maintaining health and causing disease. Some 60 secondary school, pre-tertiary and tertiary students attended the session.

Dr Seow Shih Wee kick-starting the forum.

Dr Seow Shih Wee, PRECISE’s Director (Corporate Services), kick-started the session with an overview of the National Precision Medicine (NPM) programme and its significance in transforming health in Singapore.

Sharing positive outcomes of precision medicine such as accurate disease prediction and optimised treatments, she spoke about the significance of the SG10K and SG100K studies in improving the understanding of diseases impacting Asians and the development of novel strategies to manage and treat them.

Apart from disease predisposition, the SG10K study identified genetic variations that can predict adverse drug reactions to widely used drugs – more than 1 in 4 Singaporeans were reported to be carriers of a genetic variant that increases the risk of life-threatening side effects of at least one medication. Ultimately, the studies will help narrow the Asia genomic gap and provide crucial insights into Asian diseases.

Using Denys-Drash syndrome (DDS), a rare kidney condition as an illustration, A/Prof Ng Kar Hui, Senior Consultant, Paediatric Kidney Transplantation Programme, National University Hospital, drew a compelling analogy between a transcription protein and a responsible class monitor looking after students. She explained that much like a responsible class monitor who maintains order in the classroom, keeping the rowdy students quiet and getting the reserved ones to be more participative, the DNA transcription protein that was faulty in DDS could no longer control the other genes in the cells. The DNA transcription protein was faulty due to a single DNA base (letter) change in an area of the protein that is important for detecting signals.

That single letter change results in DDS involving major consequences in kidneys and gonads, leading to kidney failure at a few months of age, failure of proper gonadal development and high risks of cancers.

A/Prof Ng Kar Hui

A/Prof Ng highlighted her Clinical Implementation Pilot which aims to implement genetic testing for glomerular diseases in local clinics. Speaking on the importance of early genetic testing, she quoted an example of a young patient with DDS, who became swollen and needed dialysis when she was just 10 days old. Doctors were unsure of the diagnosis until genetic testing was done.

“Genetic testing enabled the doctors to have a precise understanding of the specific condition they were dealing with,” A/Prof Ng added. This critical knowledge empowered them to make informed decisions about the best course of action. The specific early intervention was instrumental in shaping the patient’s care. For example, their kidneys were removed early on so that they will not develop kidney cancer. Eventually, the patient received a kidney transplant from their mother. “This is the advantage of genetic testing, we know what we need to do,” she concludes.

A/Prof Joanne Ngeow

A/Prof Joanne Ngeow, Head, Cancer Genetics Service, National Cancer Centre Singapore and Associate Professor of Genomic Medicine at Lee Kong Chian School of Medicine, NTU, shed light on the importance of genetics in cancer prevention. Drawing from her experience as an oncologist, she highlighted the challenges of treating advanced cancer cases and the need for early identification and intervention to improve patient outcomes.

“We needed something to identify people and treat them before they start to get very advanced conditions,” she said. A/Prof Ngeow likened the search for cancer prevention to the Broad Street Pump cholera outbreak in 1854. To identify the source of infection, a thorough understanding of common diseases was essential. Similarly, in medicine, researchers must first be able to understand normal variation so that they can understand patients who behave outside these norms.

She shared a compelling example of Cowden Syndrome (CS), a cancer-causing genetic condition. Dermatologists first noticed physical symptoms in the patient, Rachel Cowden, that differed from typical breast cancer cases. Through meticulous research involving twelve families, the criteria for this unique condition was mapped and the gene responsible for CS was eventually discovered.

A/Prof Ngeow also shared patients with this condition have an elevated risk of getting different types of cancers such as breast cancer, thyroid cancer, etc. This led to the development of risk-reducing guidelines for managing the increased risk of cancer seen in CS. Researchers and doctors looking after CS families also noticed an increased incidence of autism in patients with phosphatase and tensin homologue (PTEN) germline mutations.

This led to the discovery that PTEN a well-known tumour suppressor gene can also impact on neurodevelopmental outcomes. It is now well accepted that a subset of autism spectrum disorders can be caused by genetic faults and this important discovery is only possible through decades of learning from families with CS and highlights the importance of genomic research.

A/Prof Ngeow shared on the ongoing work which explores the potential of cancer drugs that inhibit specific pathways, and was found to reduce abnormal brain activity in patients with autism. This discovery was made possible because they understood the genetic basis of the condition, allowing a cancer drug to be trialled for a completely different condition, in this case, a neurological one.

In closing, A/Prof Ngeow emphasised the importance of patient observations driving discoveries and subsequent research. Understanding the genetic factors underlying various conditions allows for precise treatments and early interventions. “If you are able to find the Broad Street Pump, you can then make a big difference in terms of treatment and patient care,” stressed A/Prof Ngeow.

Overall, the key takeaways from the forum were:

  • NPM aims to address the Asian genomic gap by gaining insights into factors that contribute to Asian diseases and complement global efforts
  • Genetic testing provides early and accurate diagnosis, allowing patients to receive more precise and personalised treatments to better manage their conditions
  • Insights into patients with rare diseases can offer a deeper understanding of managing common disorders
A student in the audience during Q&A session

The students were intrigued by the real-life examples shared during the forum. A thought-provoking question was raised: “With the current advancements in medicine, is it possible to eradicate diseases before they even start?” While theoretically feasible, it lies in the ethical implementation of such procedures.

Alden, a student from Eunoia Junior College, praised the speakers for going beyond the traditional roles of doctors and contributing to the field through valuable research. Jennifer from Singapore Chinese Girls School expressed her gratitude for the eye-opening insights gained during the forum, strengthening her resolve to pursue a career as a doctor.

The forum left the students, most of whom were keen to take up a medical or STEM career, inspired by the immense possibilities that genomics holds for the future of healthcare.

Interested to learn more about the NPM programme? Visit www.npm.sg

Read more about A/Prof Ng’s and A/Prof Joanne’s CIPs:

This article is contributed by Precision Health Research, Singapore (PRECISE)


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