The foundation of every living organism – including the human body – is contained in its genes. This includes the origin and pathway of almost every known disease or abnormality, which is why an advanced and intricate knowledge of genetic makeup is essential for understanding disease, and more importantly – cures.
The Human Genome Project, completed in April 2003, resulted in a comprehensive “map” of the entire human gene complex. It has revolutionized the way scientists and clinicians study human medicine and biology.
The Genome consists of an organism’s entire DNA library. DNA – short for deoxyribonucleic acid – is a molecular building block that provides all the instructions to build and sustain the body and all its functions.
With this information scientists can now study the complex and intricate interactions that direct the physiology and functioning of the human body.
The mainstay of genomics research is the DNA microarray, which allows scientists to examine thousands of genes at once, and study their activity and interactions. Microarrays, also called “gene chips,” are created by arranging gene fragments on a single “chip,” usually a glass, silicon or nylon membrane. The thousands of genes on a single DNA microarray chip together represent large portions of the genome of an organism, and provide a snapshot of the organism’s genetic workings. [1]
The Human Genome project has brought us new diagnostic tools and therapies by aiding scientists in detecting and analyzing genetic abnormalities. Individualized deviations can point to the origin and development of a vast range of diseases, such as cancer. An understanding of the human genome is helping to explain why cancers in some people respond to treatment, while the same treatment may be ineffective for others. It has ushered in the age of personalized medicine, which, though just beginning, will soon allow clinicians to customize drug therapies to an individual’s genetic make-up, a field known as “pharmacogenomics”.
To quote the National Human Genome Research Institute: “…the role of genetics in health care is starting to change profoundly and the first examples of the era of genomic medicine are upon us.” [2]
These below examples of advances in genomics research demonstrate the value of genomics and personalized medicine:
Genomic research has created a new pathway for identifying promising drug targets. For example, The New England Journal of Medicine described one study in which gene sequencing led to the discovery of a mutation specific to melanoma. This led to the development of a drug designed specifically to inhibit that mutation, resulting in tumor regression in the majority of patients in one clinical trial. [3]
Ohio State University researchers and collaborators have identified a tiny gene mutation in human liver cells that affects the level of a liver protein responsible for processing between 45 percent and 60 percent of all medications currently prescribed for patient use. [4] The mutation was shown to significantly determine how the patient’s body would metabolize most drugs, greatly affecting the amount of dose needed for a therapeutic response, or in some instances, warding off a too-high, toxic dose. Identifying this genetic mutation in prospective patients could serve as a bio-marker for how much of a dose to give.
Genomics has also changed epidemiology research – a time-honored method that examines populations to uncover disease trends – bringing us what is known as Genome-wide Association Studies or GWAS. In GWAS studies, scientists scrutinize the genome of populations to identify specific genomic changes that appear to be associated with the disease.
Scientists have been able to locate a genetic variant linked to an increased risk for stroke by examining the genomes of nearly 5,000 people. [5] That study also revealed new details about a key metabolic pathway that underlies cardiovascular diseases.
The results of the study provide a greater understanding of the development of stroke and cardiovascular disease – and unlike animal studies which may reveal possible pathways in animals – these findings are human relevant and far more likely to lead to treatment or cures.
Genomics holds huge promise for the future. As scientists gain a fuller understanding of human genetics and the function of the genome, we will learn more about the intricacies of the most basic components of life, and ultimately, how these elements can yield answers for diseases that still remain uncured.
[1] Genome Resource Facility, London School of Hygiene and Tropical Medicine, “What is DNA microarray technology?” http://grf.lshtm.ac.uk/microarrayoverview.htm#m1, retrieved May 28, 2014
[2] National Human Genome Research Institute, “ Implications of Genomics for Medical Science”
http://www.genome.gov/18016863, web retrieved July 15, 2014.
[3] Hudson, K. L. (2011). "Genomics, Health Care, and Society." New England Journal of Medicine 365(11): 1033-1041. http://www.nejm.org/doi/full/10.1056/NEJMra1010517
[4] Science Daily, May 11, 2010, “Tiny mutation might help indicate proper dosage for half of all drugs,” May 11, 2010, http://www.sciencedaily.com/releases/2010/05/100510161334.htm
[5] National Institutes of Health: NIH News, “Researchers discover underlying genetics, marker for stroke, cardiovascular disease,” March 20, 2014, http://www.genome.gov/27556706