For several years, scientists have looked to the intricacies of the human genome for answers surrounding the mystery of disease and illness. During this insight-driven exploration, they uncovered genes and the unit of heredity itself – the DNA.
The elucidation of this compound’s (DNA) three-dimensional structure by molecular biologists, James Watson and Francis Crick in 1953 from crystallographic data produced by Rosalind Franklin and Maurice Wilkins, built the foundation of genomics, which would in turn lead the radical revolution of universal healthcare through precision medicine almost 60 years later.
The first discovery of the DNA followed by the birth of genomics a few decades later has spurred on various subsets of scientific fields, such as genome sequencing, pharmacogenomics, proteomics, and bioinformatics, to name a few, which all feed into its mighty interdisciplinary operation.
Genomic sequencing in particular has evolved rather rapidly in the last few years, in most part, due to the expeditious nature of technological improvements, a most astounding feat contrary to its staggering progression in the earlier stages of its inception.
In recent years, precision medicine has exposed the flaws associated with a one-size-fits-all approach to treatment and proposed a more personalized style of healthcare for all. By tailoring treatment and medication to the specific genetic makeup of subpopulations, it is possible to decipher their predisposition to diseases, detect and more accurately diagnose these risks, guide prevention and prevent recurrence of future conditions.
Successfully tailoring treatment to individual genetic makeup would cause a revolution of medical care, but requires the discovery of the relationship between rare variation in the human genome and their resulting impact on individual health and mendelian disease.
Each step in the path to better appreciating the elements of the genome and its interwoven interactions has led to increased sensitivity in approaches to interrogate individual genomic variations from insights revealed by its disciplinary branches.
Technologies like Chromosomal microarray (CMA), a first-line genetic test, and Whole Exome Sequencing (WES), a technique that uses next-generation sequencing (NGS) technologies, have both respectively redefined genomics in the past few years by offering increased resolution for genome-wide detection of copy number variants (CNVs), and thorough simultaneous interrogation of almost all 20,000 human protein-coding genes for rare variations known or suspected to be causes of disease. On the other hand, Whole Genome Sequencing (WGS) which involves sequencing the entire genome, both coding and non-coding proteins of the DNA, offers an even more comprehensive analysis by enabling identification of structural rearrangements, detecting non-coding variants, as well as disorders caused by repeated sequences of DNA (DNA repeat) and mitochondrial mutations.
Whole genome sequencing offers applicable insights from a unique vantage point that can be translated into:
- Personalized plans to treat disease based not only on the mutant genes causing it, but also other genes in a patient’s genome.
- Less toxic treatment options for chemotherapy since therapy is tailored to patients’ cancer genotyping results which identify mis regulated genes.
- Insights highlighting previously unknown genes and mechanisms that could possibly be contributing to a disease state which traditional genetic testing could overlook.
- The effects lifestyle or environmental changes contribute to genetic predispositions.
- Insights derived about drug efficacy or adverse effects of drug use on an individual or population’s system.
More robust genetic investigations such as Whole Exome Sequencing and Whole Genome Sequencing are recognised as more preferable options, especially where the range of suspected causative genes is wide. This method avails to the healthcare system an extensive survey of the genomic information of individuals which can be used to provide customised, immediate and future medical care.
Limiting research to only the most accessible regions of the genome introduces an observational bias that genome-wide analyses do not accommodate. Due to its unbiased approach of analysis, presupposition of a particular gene, variant, or locus, as etiologic for a given condition is not acknowledged, as all genes and their associations are taken into consideration.
Understanding variation within the human genome to differentiate normal variants from those that cause diseases is challenging, as every human genome contains millions of genetic variants compared with the reference sequence, and most diseases have a genetic origin.
However, the application of new technologies in genomics relevant to a host of conditions ranging from cancer, rare diseases to mendelian diseases, enhances the understanding of disease conditions and their molecular mechanisms, and therefore the capacity for personalised interventions for all populations of the world.
With the addition of its most recent molecular sequencing platforms from Illumina, such as the NovaSeq 6000, 54gene aims to delve deeper into the regions of the genome to better understand the origins and causes of diseases prevalent on the African continent and gain insight into practical approaches to improve healthcare and treatment across the world.
2. The rise of the genome and personalised medicine. Helen K Brittain, Richard Scott, Ellen Thomas