Over the past twenty years, the field of genomics and its application in healthcare have drastically changed. The decoding of personal genomes, once a costly process, conducted only in large research institutions, has now become widely accessible. This progression is largely due to the decreased costs of genome sequencing technologies, especially with the advent of next-generation sequencing.
This increased accessibility has sparked numerous large-scale projects, aiming to use genetic data to enhance healthcare services. By marrying technology with biology, we’re now seeing initiatives on a population scale for whole genome sequencing. These efforts aim to crack the genetic codes of various populations, leading us closer to understanding the genetic underpinnings of various diseases and potential cures.
Personal Genomics And Personalised Medicine
Personal genome sequencing stands as a powerful tool. It enables us to fine-tune treatments based on individual genetic profiles and predicts a person’s susceptibility to certain diseases. This push towards personalised medicine could be groundbreaking, potentially revolutionising our approach to healthcare and treatment.
- Understanding Genetic Testing: In the past ten years, we’ve seen major improvements in genetic testing. Nowadays, it’s not just one gene that gets tested, but many at the same time. A method called whole exome sequencing, for instance, lets us look at around 1% of our entire genome, which includes several areas where proteins are made.
- Applications of Genetic Testing: These advanced tests give us loads of information, not just about one part of our genetic material, but all of it. This wealth of information can help scientists identify genetic diseases, figure out how we might react to certain medications (pharmacogenomic assessments), determine if we’re carriers of certain diseases, and even trace our family tree.
- Dealing with Incidental Findings: One interesting byproduct of these comprehensive tests is that they can sometimes reveal unexpected genetic abnormalities. These are known as incidental or secondary findings. However, not all of these surprise results are useful or relevant to the person being tested. This has sparked a conversation among scientists about whether people should have access to these findings.
Understanding Incidental and Actionable Genetics
The American College of Medical Genetics and Genomics (ACMG) made a proposal back in 2013. This recommendation was for labs that were running whole exome or whole genome sequencing. They suggested that incidental findings – unplanned discoveries in a test that was not initially ordered for that purpose, but can be quite significant – that relate to certain health conditions and diseases should be shared with the individual. This is because this information could potentially be helpful to them.
- Consultations and Conditions Covered: The ACMG didn’t just make this recommendation out of the blue. It was the result of year-long discussions with a variety of stakeholders. The conditions which they decided to include in their recommendation were genetic cancer syndromes (like familial breast and ovarian cancers and familial gastrointestinal cancers), along with common cardiac and metabolic diseases.
- Expansion of the List and Population-Based Studies: Over time, the ACMG has continued to add more conditions to this list. The most recent version, published in June 2023, covered 97 disorders and 81 genes that span conditions like cardiovascular and metabolic disorders and cancer. But the ACMG isn’t the only group studying these incidental findings. Researchers worldwide are looking at the frequency of incidental and actionable genetic information in their populations. They’re doing this by analysing the data from large-scale genome-sequencing programs being run in many countries.
- Prevalence Estimates and Findings in the Indian Population: Estimates vary, but the general consensus is that this type of information is found in about 1% to 3% of people. It’s worth noting that this rate can vary among different populations and different versions of the genes in the secondary findings. In India, for example, these studies have highlighted two diseases that are often overlooked – cardiac channelopathies and familial hypercholesterolemia. The rate of these conditions in the Indian population is estimated to be about 1 in 100 and 1 in 150, respectively.
Genomic Sequencing And Lifespan
Researchers have recently carried out an in-depth study of over 57,000 genomes from Iceland’s population. Their findings indicated that about 1 in 25 people in the group might carry genetic variants that could be acted upon to potentially enhance their lifespan.
- Variants and Lifespan Reduction: These individuals with actionable genetic variants, however, exhibit a reduced average lifespan by one year compared to those without these variants. Moreover, a striking observation is that 10% of these individuals with actionable variants have a considerably shorter lifespan.
- Impact of Cancer-Related Genotypes: When adjusted for the type of disease, it was noted that individuals with actionable genotypes related to cancer had three fewer years of life on average. Especially within this group, 10% of individuals died about eight years earlier on average.
- Implication of BRCA1 and BRCA2 Genes: The major contributing factor to this reduced lifespan was found to be the presence of BRCA1 and BRCA2 genes. The mutations in these genes are known to elevate breast cancer risk.
- Potential of Genome-Sequencing: As genome-sequencing becomes increasingly accessible and affordable, the potential for widespread population-scale sequencing and newborn screening initiatives is on the horizon. This would allow a significant portion of the population to gain crucial insights into their health, empowering not only individuals but healthcare systems to take proactive, precise, and effective steps in disease treatment and prevention.
Source: You had your genome sequenced and found something – now what? (The Hindu, January 1, 2024)