Genetic testing and genomic studies are helping people around the world lead healthier lives and fight disease and infection on a global scale. Exponential advances in high throughput genomic technologies and ‘big data’ analysis have powered large-scale data initiatives such as the 1000 Genomes Project, the 100k Wellness Project, and many others. This explosion of data and technology has enabled development of more rapid and scalable tests that can survey entire genomes and accurately pinpoint genetic changes to a single base pair. As a result, the emerging discipline of genomic medicine, which makes use of personal genomic information to enable more individualized care, is transforming clinical practice.
In its broadest sense, genetic testing refers to direct or indirect analysis of genetic variations and changes in sequence, structure or expression of heritable genes. Depending on the purpose, genetic tests can be carried out on virtually any biological sample that contains intact genetic material, gene products, or related metabolites.
In clinical and regulatory contexts, the term genetic testing is typically reserved for tests that focus on inheritance of a particular trait or single gene—for example, to assess whether an individual has an increased likelihood of inheriting a certain single-gene disorder like cystic fibrosis or Huntington disease. Genetic testing is considered distinct from genomic testing, which involves analysis of changes across a panel of genes or an individual’s entire genome – for example, when assessing a tissue biopsy to determine which genes are driving tumor growth in a cancer patient.
Thousands of human disorders and diseases are now known to result from specific genetic alterations or have a strong genetic component. DNA sequence variations inherited or acquired as a result of diet, lifestyle or environment can determine whether we are susceptible to a particular disease, pathogen or allergen. Our genes also have an impact on how we respond to various medical interventions and treatments, including vaccines, blood transfusions, organ transplantations, pharmaceutical drugs, and cancer therapies—to name just a few.
Genetic testing and genome-wide analyses are therefore informative for diverse applications in human health, and across many disciplines.
This century’s explosion in genetic testing and genome-wide analysis has been fuelled by continued development of more sensitive, rapid and cost-efficient methods of analyzing genetic material. In particular, chip-based microarray approaches and NGS technologies have enabled more affordable and comprehensive genome-wide analyses at increasingly high resolution. As a result, genetic testing is more accessible and more widely used than ever before.
Genetic testing methods of choice vary according to the type of information required, the level of sensitivity needed, and the time it takes to get results. Clinical genetic testing approaches fall into 3 main categories: molecular, cytogenetic and biochemical:
With the emergence of DNA microarray chip technology in the mid-1990s, it became possible to analyze thousands of genetic markers in a single run.
Microarray-based gene expression profiling (GEP) identifies disease-associated changes in gene expression by analyzing differential hybridization of cDNA to panels of target sequences arrayed on a chip. Microarray technology can also be applied to microRNA (miRNA) profiling, for example in cancer classification and earlier identification of carcinoma of unknown primary (CUP) origin.
Completing the first human genome reference sequence took 13 years and around $1 billion. With the latest NGS solutions and advanced bioanalytics, it is now feasible to obtain whole-genome test results in under a day14,15, and the cost of NGS continues to plummet as we enter the era of the $1000 genome16. NGS is without doubt a game changer in genomics and applied fields, including precision medicine and companion diagnostics.
While NGS technologies vary, what they have in common—and what sets them apart from conventional Sanger sequencing as truly disruptive “next generation” solutions—is their ability to run unprecedented numbers of sequencing reactions in parallel on a micro scale that uses far less starting material. The result is significantly faster and more cost-efficient sequencing.
The rapid evolution of sequencing technology in the 21st century has given researchers unprecedented power to understand human health and disease at the biomolecular level, discover better therapeutic targets, and transform clinical care. The following are a few key areas where NGS technology is having significant impact in biomedical research, healthcare and clinical practice.
NGS-driven genomic studies are unlocking a wealth of new pharmacogenomic insights that are being used to turn the old ‘one size fits all’ approach to medicine on its head. Rather than try to tailor treatments uniquely to individual patients, precision medicine makes intelligent use of genomic information to understand and predict how individuals will respond to particular drugs and therapies based on their genetic makeup. As NGS becomes more universally available, more comprehensive genomic data can be collected using WGS and WES methods, and integrated into electronic health records and genomic databases. At the same time, large-scale genomic data initiatives continue increase the amount of genomic information available for pharmaceutical and clinical diagnostic applications.