One Genome through a Lifetime

Age 21: WGS stored

Sarah is a healthy woman, who undergoes whole genome sequencing (WGS) as her 21st-birthday present gifted by her parents. Her WGS data was stored without analysis or clinical interpretation at the time.

Age 28: Carrier screening

As Sarah gets married and plans to have a family at the age of 28, she considers reproductive carrier screening to reduce the chance of her and her partner having a child with genetic disorders. Her WGS data is interrogated for carrier status of more than 1000 recessive and X-linked conditions. Following screening, they proceed to have 2 healthy children.

Age 35: BRCA1 mutation found

At the age of 35, Sarah learns about her family history of breast cancer. Several of her paternal aunts have died from breast cancer. Sarah is concerned about her own risk and wants to do everything she can to protect her health. She seeks genetic counselling, and requests to have her WGS data analysed for mutations in high-risk breast cancer predisposition genes. The results show a disease-causing mutation in the BRCA1 gene. This result places Sarah in the high-risk category for developing breast and ovarian cancer.

With this information, Sarah and her doctor are able to create a personalised plan for her health. She decides to undergo regular screenings and surveillance, including mammograms and MRI's, aiming to detect cancer early when it's most treatable.

Age 36: Preventive surgery

The following year upon screening, Sarah is found to have early breast cancer in her right breast. Due to her BRCA1 genetic status, Sarah is at an increased risk of additional cancers in either breast, as such she is offered bilateral mastectomy with breast reconstruction as a treatment option. Sarah is able to make an informed decision based on her genetic status and elects to have this surgical procedure that not only removes her breast cancer but also significantly reduces her future breast cancer risk. 

Genomic profiling of her breast cancer cells is undertaken following breast surgery. The results show mutations in the PI3K/AKT/mTOR pathway, informing the choice of targeted treatment if needed for Sarah in the future, for example, if Sarah develops a relapse of breast cancer elsewhere.

Pharmacogenomics variants are also analysed from her WGS data, to predict her response and metabolism of more than 200 therapeutic drugs. The results are used to guide the dosage of her adjuvant chemotherapy as well as tamoxifen; and to tailor selection and optimal dosing of supportive therapy including antiemetics and postoperative pain management.

In addition to Sarah’s personal health implications, the identification of the BRCA1 mutation has implications to her wider family who can now access the option of predictive genetic testing to inform their personal risk, health management, and reproductive planning.

Age 40+: Mental health, cardiac risks

When Sarah turns 40, she makes an informed decision to undergo risk-reducing bilateral salpingo-oophorectomy to reduce her ovarian cancer risk associated with the BRCA1 mutation. 

Sarah develops Major Depression following the surgery and is commenced, by her psychiatrist at point of care, on an anti-depressant that is compatible with her pharmacogenomics profile. Sarah shows good response to the first antidepressant prescribed and is able to achieve remission in the first 4 months of depressive symptoms.

Age of 55

At the age of 55, Sarah develops chest pain and shortness of breath. She undergoes a variety of tests which are not conclusive in reaching a diagnosis. Her doctor resorts to genetics and arranges to have her WGS data analysed for an underlying genetic cause. 

The results of the genomic analysis reveal that Sarah has a genetic mutation that puts her at an increased risk of developing heart disease and life-threatening heart rhythm. With this knowledge, her doctor is able to tailor her treatment to target her specific risk factors and prevent the onset of heart disease. Sarah is put on a preventive medication to keep her heart rhythm under control and given lifestyle recommendations to reduce her risk of sudden death.

Genomic testing provides Sarah with a more complete understanding of her health and leads to timely and more accurate diagnosis and treatment of her symptoms. It also allows her to take proactive steps to prevent the onset of other diseases.