Genomic medicine: cracking genomes to cure ‘incurable’ diseases

We are on the precipice of realising the true potential of genomics studies. Following completion of the Human Genome Project six years ago, huge strides have been made in understanding how the genome works, shedding light on disease pathogenesis and forging therapeutic efforts. In this article, Pushpanathan Muthuirulan explains how genomic medicine has the potential to transform clinical treatment.


JUST SEVERAL years ago, the use of genomic technologies to better understand and treat genetic disorders was largely out of reach for most researchers and clinicians due to high costs and technology limitations. However, recent advances in more cost-effective, high-throughput genetic sequencing technologies, which facilitated the effective completion of the Human Genome Project (HGP) in 2013, have provided a complete genetic blueprint for building a human being. This has enabled scientists to better understand how the genome works and how differences between individuals’ genomes can influence health and disease. The new era of genomic medicine has opened our eyes, enabling us to understand diverse characteristics of most common and rare human genetic diseases and help inform advances in biomedical research and drug discovery. Thus, the field of genomic medicine is progressing at rapid pace. Genomics will likely become a routine part of clinical practice; expanding the precision medicine effort towards curing ‘incurable’ diseases.

Several genomic diagnostic testing methods have been successfully developed for various cancer types”

Genomic medicine is an emerging field of medicine that utilises an individual’s genetic information as part of wider medical practice. The practice of genomic medicine started largely after the completion of the HGP, which generated an abundance of information on diverse genetic characteristics relevant to an individual’s current and future health. The fundamental premise of genomic medicine is to use genome-wide analyses to potentially match an individual patient’s genetic alterations with a therapeutic drug that targets those alterations. The translation of genomic information into mainstream medical practice has been largely catalysed by the advent of Next-Generation Sequencing (NGS). This offers tremendous possibilities for whole-genome, targeted or whole-exome analyses. It also serves as the most powerful approach for integrating genomic analysis modalities into patient care for diagnostics and therapeutic decision-making.1-3

Generally, human disease may involve thousands of genes across multiple cell types in different regions of the body; hence the tools currently available for diagnosis and treatment would not be sufficient to meet the challenges and complexities associated with the initiation and progression of complex diseases.4 In recent years, genomic medicine has made a profound impact on numerous disciplines including infectious diseases, clinical pharmacology, oncology, cardiology, neurology, genetics, population genomics, evolutionary biology, informatics and public health genomics. However, successful implementation of genomic medicine into clinical practice remains challenging, as it requires overcoming common obstacles encountered during integration of genomic data into routine healthcare systems and implementation of efficient strategies to educate stakeholders about the importance of genomic services in patient healthcare.5,6 One barrier to adoption of genomic medicine includes inconsistent modes of interpreting a patient’s genomic information. For instance, each human carries several hundred potentially pathogenic variants in their genome that contribute to a wide range of diseases; the major challenge in this context is to understand which of these variants are relevant to the patient’s disease. This requires a powerful analytical approach and high-performance computing features alongside input from a clinical scientist for accurate phenotyping and understanding of diseases. Other barriers to successful implementation of genomic medicine into healthcare systems includes ambiguous organisational policies and criteria for use, ethical and economical regulation, lack of knowledge by clinicians to interpret patient genomic testing results and lack of understanding by patients about the implications of the clinical results.1

This article aims to discuss the promises and pitfalls of genomic medicine by focusing on complex diseases, highlighting the importance of implementing genomic medicine into daily clinical practice to individualise risk predictions and treatment decisions.

Genomic medicine in cancer diagnosis

Recent advances in more cost‑effective, high-throughput genetic sequencing technologies have provided a complete genetic blueprint for building a human being”

The genetic changes that accumulate over a person’s lifetime would result in acquired or somatic changes that account for 90-95 percent of cancers that exist today. Cancer genomics is an emerging research area that has enabled scientists to study cancer genomes to understand abnormalities in genes that drive growth and development of different types of cancer. Cancer genomics research has improved our knowledge on the biology of cancer and led to the development of new approaches for diagnosis and treatment. It has also provided deeper insights into the molecular basis of cancer growth, chemoresistance and metastasis. Identification of cancer-inducing genetic and epigenetic changes in a patient’s genome has also facilitated the development of new therapies targeting these changes and helped to identify those patients that may benefit from these therapies. Several genomic diagnostic testing methods have been successfully developed for various cancer types including colorectal cancer, adrenocortical carcinoma, gastrointestinal stromal tumours, thyroid cancer and Burkitt’s lymphoma.7 Cancer genomics has mainly used the latest NGS technologies to map the diverse landscape of genetic alterations in cancer cells, providing a strong foundation for understanding the genetic and molecular basis of this group of deadly diseases. Thus, an increased understanding of genomes in cancer cells would improve diagnosis and accelerate the medical and surgical management of cancer. Genomics and cardiovascular diseases Genomics is rapidly evolving, and it offers tremendous potential to understand complex cardiovascular disease (CVD) conditions, including congenital heart syndromes, valvular diseases, inherited cardiomyopathies, hypertensive syndromes and heart failure. An increasing number of genetic variants, epigenetic changes and environmental factors have been linked to CVD, making it vital to develop an effective and accurate system to understand the mechanism of diseases. Integrating genomic information into healthcare systems would provide insights into specific pathogenetic pathways to help guide diagnosis and therapies for individualised treatment.8 The implementation of genome-driven personalised cardiology into healthcare practice would shed light on CVDs at both the molecular and cellular level, thus yielding more clinical benefits. In recent years, most CVD defects have been identified by high-throughput genomic technologies that would offer customisable approaches to prevent, diagnose and manage the disease. Recent advances in novel sequencing technology, epigenetics and transcriptomics approaches, along with unprecedented co-operative efforts, could potentially eradicate CVDs, thus improving human health and wellbeing.9 Thus, the rapid accumulation and integration of genomic information into healthcare holds great promise for generating insights into the complexity of CVDs.

Infectious disease genomics

Advances in NGS technologies are contributing significantly to the development of more effective, precise and personalised therapies for the treatment of infectious diseases.10 They are also serving to strengthen our knowledge on how interactions between pathogen and human genetic factors could potentially contribute to differences in individual immunologic responses. There is also growing interest in the application of genomics to infectious disease management and epidemics, which are among the most significant global public health threats.11 Rapid and high‑throughput sequencing of pathogen genomes would provide deeper insights into disease outbreaks, disease transmission, emerging drug resistance and drug target identification for newer therapeutics. In addition, understanding the novel interactions between host and microbe would reveal individualised host-microbiome profiles that could be integrated with other genetic technologies (eg, CRISPR) to enhance precision medicine.12,13 The main challenge regarding implementation of genomic medicine in infectious disease management is lack of efficient, innovative data management and analysis methods. Successful implementation requires computational resources and bioinformatics expertise to accommodate and analyse the large amounts of biological data in a meaningful way.14 Currently, genomic research is improving our knowledge on infectious disease pathogenesis and immune response, which will help guide future drug development and treatment strategies.

Integrating genomics into evolutionary medicine

The application of genomics in evolutionary biology was suggested several years ago and is already providing useful insights into the cause of disease. In evolutionary genomics, comparing genomes across different species enables scientists to infer those genes or gene regulatory elements that are important for basic biological processes to have been maintained over the course of evolution. For instance, identifying genes that are present in humans but not its closest mammalian and primate relative will help scientists to uncover the genes that are unique to human beings. However, the successful integration of genomics into evolutionary medicine is yet to happen. There are certain obstacles hindering the development of evolutionary genomics medicine and considerable challenges in predicting phenotypes from genotypes.15 In recent years, genome-wide association studies (GWAS) have proven successful in detecting associations between genetic variants and diseases. They have also helped researchers to investigate the effects of selection.16 Furthermore, understanding evolutionary processes such as genetic drift, gene overlap, migration, mutation and recombination will provide better understanding of disease-causing regulatory elements and genes in patients and this effort will also greatly facilitate diagnosis and treatment of complex diseases.


Neurogenomics is another emerging area of science that has enabled scientists to understand how the genome of an organism influences the development and function of its nervous system. Neurogenomics integrates both functional genomics and neurobiology to understand the nervous system from a genomic perspective. Defects in the formation of neurons during development can cause mental retardation and thereby decline the cognitive function in the brain, leading to memory loss. Neurogenomics aims to understand the molecular changes that occur within the brain during cell development, senescence and diseases.17 Thus, identifying the molecular defects in brain cells will provide new avenues to overcome neurological disorders and help us understand the mechanistic basis of disease association.


Genomic medicine has tremendous potential to provide novel diagnostics and therapeutics for patients suffering from complex diseases. The implementation of genomic medicine into clinical healthcare systems presents significant challenges that will likely require the efforts of joint initiatives to be successfully addressed.

About the author

Pushpanathan Muthuirulan is currently a Research Associate at Harvard University studying the developmental and genetic basis of human height variations using functional genomics approaches. Previously, he worked as a Postdoctoral Researcher at the National Institutes of Health, where his research focused on developing state-of-the-art technologies using CRISPR-Cas9 and super‑resolution microscopy to map neural circuits that involves visual motion information processing in Drosophila. His expertise lies in omics technologies, drug discovery, neuroscience and developmental and evolutionary genetics.


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