Genomic Testing and the Future of Medicine

Introduction

The genetic makeup determines an individual’s characteristics such as height, skin tone, and hair color, or phenotype. Scientists are beginning to assess the basis of various health conditions using genetic testing. Tools and techniques can scan for genetic predisposition of certain diseases, including cancer, neuromuscular, rheumatologic, and infectious conditions. Knowledge about a person’s genetic makeup assists in the early diagnosis and treatment of disease and increases the efficacy of pharmacotherapy.

The future of medicine will likely include genomic testing to drive the detection and treatment of diseases. Advances in epigenetic testing may allow scientists to predict the risk of cancer, heart disease, and other conditions. Genomic testing may catapult healthcare into an era of personalized medicine.

Genomics and the Age of Computers

The marriage between supercomputers and genomics was inevitable and instrumental. The amount of information stored within our genetic code, although finite, is vast. Computers were necessary to assist in sequencing, pattern determination, and modeling. Beginning with the Human Genome Project, the time it takes to completely sequence the human genome decreased from fifteen years to a little more than an hour.

Faster sequencing speeds brought the cost down substantially; Steve Jobs was one of the first to have his genome sequenced at the price of approximately $100,000. Now, this process would cost $100 (Fikes, 2017). Newer methods contributed to the end-to-end sequencing of the human X chromosome, which was otherwise impossible before (Miga, 2020).

In 2012, scientist at the University of Leicester printed the complete human genome. Something that has a combined length of 200 nanometers (1 nm = 10 -9 meters) took 130 volumes to fill with its Cs, Gs, As, and Ts. Computers are capable of storing and accessing information with a speed that was previously unimaginable. Handling and evaluating the vast amount of information could not be possible without them. Artificial intelligence programs may simplify the determination of patterns.

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Pharmacogenomic Testing

Pharmacogenomic or pharmacogenetic testing refers to the study of genes and how they influence the body’s reaction to certain medications. An individual’s genetic layout determines how they look and forms the basis for understanding biochemical pathways, including medication response. Genetics account for the variation in individual side effects, efficacy, and dosing concentrations. Pharmacogenetic testing assists physicians and other healthcare providers in tailoring a treatment plan and drug dosage regimen most suitable for the patient.

An individualized approach in medicine results in better and more favorable treatment outcomes. Currently, pharmacogenetic testing is available for several medications (See Table Below). The tests can be run before starting the treatment or when the medicine produces adverse effects. [1]

DrugsGenes
Warfarin (anticoagulant or blood thinner)CYP2C9 and VKORC1
Plavix (anticoagulant or blood thinner)CYP2C19
Antidepressants, AntiepilepticsCYP2D6, CYPD6, CYP2C9, CYP1A2, SLC6A4, and HTR2A/C
Tamoxifen (breast cancer)CYPD6
AntipsychoticsDRD3, CYP2D6, CYP2C19, CYP1A2
Drugs for Attention Deficit Hyperactivity Disorder (ADHD)D4D4
Carbamazepine (antiepileptic)HLA-B1502
Abacavir (anti-HIV) for hypersensitivityHLA-B5701
OpioidsOPRM1
Statins (familial hypercholesterolemia)SLCO1B1
Drugs for childhood leukemiaTMPT
Table 1: Currently available Genetic tests

Pharmacogenetic testing is a potent predictor of drug interaction and adverse effects. The healthcare industry saves the expenses of ineffective pharmacotherapy and harm from adverse drug reactions. [2]

Genetic Testing to Determine Predilection to a Certain Disease

Genetic testing is not just limited to therapy. Physicians can use testing to predict an individual’s susceptibility. Inheritable genetic variations and mutations determine genetic predisposition to a particular health condition. While some people with a genetic risk factor develop disease following specific environmental exposures, awareness can be helpful.

Varying genetic findings influence the magnitudes of diseases. Moreover, specific genes play a significant role in regulating the onset of illness, while other related genes only play a minor role. For instance, BRCA1 and BRCA2 gene mutations increase the risk of an individual developing breast and ovarian cancer. However, BARD1 and BRIP1 gene mutations do not contribute significantly to the risk of developing breast cancer. Despite having a slight chance for diseases, multiple minor genetic mutations may pose a  cumulative effect. 

In most cases, genetic predisposition does not increase the risk of diseases on its own. Disease develops as an interplay of genetic, environmental, and lifestyle forces. While genetic predisposition is inevitable, lifestyle and environmental risks are vital forces to emphasize disease prevention. Abstinence from alcohol and tobacco, optimal weight, and early and frequent screening, particularly for high-risk individuals, are essential measures to reduce the risk of genetically determined diseases. [3]

23andMe offers DNA testing services for anyone who wants to know more about their ancestry and genetic traits. The Personal Genetic Testing Kit only requires a person’s saliva followed by its shipment to 23andMe lab for detailed analysis. The DNA analysis report returns within 4-5 weeks.

The genomic testing of BRCA1/2 can be useful to determine the risk of breast cancer.
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Epigenetic Testing to Determine the Degree of Risk for Inflammation and other Health Conditions

Epigenetics refers to alterations in gene expression that cause any changes or mutations in the DNA sequence. Environmental and lifestyle factors may lead to epigenetic modification. One of the common forms of epigenetic modifications is DNA methylation. Epigenomes are those substances capable of modifying genetic expression by acting upon factors including DNA and histones. Epigenomes include tobacco, exposure to radiation, dietary factors, toxins, and physiologic changes during aging. An example of epigenetic modifications is in patients with colon cancer. Their cells show DNA hypervariability and hypomethylation. Conditions like rheumatoid arthritis and other autoimmune diseases are associated with epigenetic changes such as DNA methylation. [4]

Assessing epigenetic changes can serve as disease biomarkers. They may aid in diagnosis and serve as a way to monitor the status of a disease and its treatment outcomes. Doctors can sample various specimens, including urine, serum, plasma, breast milk, and fresh, frozen, or formalin-fixed paraffin-embedded (FFPE) tissue. For instance, methylated Septin9 obtained from peripheral blood is used as a biomarker to detect colorectal cancer early in its course. Various techniques, including methylation-specific-MLPA, MethyLight, MS-HRM (methylation-sensitive high-resolution melting analysis), pyrosequencing, miRNA, qRT-PCR, and histones, are used for assessing epigenetic modulators. [5] 

Other Trends in Personalized Care

Personalization of treatment and care plays a crucial role in reducing the burden of disease. Personalized medicine, also known as precision medicine, is tailored according to the individual’s genetic makeup and presenting health status. The optimal microbiome, more importantly, the gut microbiome, determines an individual’s overall health. Antibiotics and other environmental stressors may disrupt the gut microbiome and be responsible for ineffective immunotherapy and chemotherapy. [6]

GI-MAP is an example of a diagnostic tool that can determine pathogenic organisms in the gut by performing a fecal analysis. The test includes an assessment of which organisms, or their associated metabolites, are present in a fecal sample. There is also a DNA analysis to determine the load of organisms. GI-MAP enables the physicians to identify the pathogen responsible for causing the disease. Henceforth, physicians can prescribe medications and administer other therapeutic modalities targeting the specific pathogen. [7]

Conclusion

A personalized approach to diagnosis and treatment, often called precision medicine, offers individuals the possibility of tailored care. This customized medicine yields better treatment outcomes and lessens adverse effects. Genetic testing will likely form the basis of personalized medicine and may become a routine part of screening and evaluating patients in the future.

References

  1.  https://medlineplus.gov/lab-tests/pharmacogenetic-tests/
  2. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3765014/
  3. https://medlineplus.gov/genetics/understanding/mutationsanddisorders/predisposition/
  4. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC3715917/
  5. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6733278/
  6. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6512898/
  7. https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7660239/

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