Jan 20

Genomics in Medicine

The Gene Sequencing Future Has Arrived


Merriam Webster defines genomics as:

A branch of biotechnology concerned with applying the techniques of genetics and molecular biology to the genetic mapping and DNA sequencing of sets of genes or the complete genomes of selected organisms, with organizing the results in databases, and with the applications of the data (as in medicine or biology)

Many of us have just started to hear about the advances in genomics in some fashion.

These advances are on the leading edge of technology. The growth in this field is happening all around us. This article will provide a little review and then address a few of these advances.. In the interest of simplifying, the complex biochemistry will not be extensively addressed in this writing. We will look at the basics of biochemistry in future articles.

DNA was first discovered in the late 1800’s. Then in 1957, Francis Crick and James D. Watson discovered and described the double helix structure of DNA along with some of the molecular biology and chemistry that are all related. This article is more of a general overview of genomics and some recent advances in the field

When Watson and Crick made these discoveries, they opened a door more powerful than the discovery of nuclear fission, the Atomic Bomb. The consequences of their discoveries and the subsequent science devoted to those discoveries make it the most important discovery humankind has ever made – according to some of the current experts in the field and Watson himself.

The pursuits related to this discovery, the accompanying biochemistry, and many other rapidly growing branches of genetic science, have been going on since that first breakthrough.

The first complete genome sequenced was that of a common bacterium called Hemophilus Influenzae – good old H. Flu. H. Flu is a bacterium with which most of us in the medical field are familiar. It is capable of causing infections from meningitis to pneumonia when it is the agent. Identified years ago, Hemophilus Influenzae is a very familiar and notorious organism. A Nobel laureate, named Hamilton Smith, one of the Human Genome project leaders, had been working on this organism and its DNA for decades because of its prevalence, and it was chosen as the first organism for sequencing because of the high quality DNA libraries he could provide.

In modern genetics, the genome is the entirety of an organism’s hereditary information stored in the DNA, including all of its genes. The plan for sequencing the entire human genome was initialized in 1987 and was funded and planned for 15 years to accomplish the goal. Work started about 1990 and was declared completed in April of 2003. It cost 2.8 Billion dollars. It was a big event, you might remember seeing or reading about it.

The Basics of What We Are Doing

As we began the sequencing of genomes for organisms in our world, discoveries have literally exploded and are driving technological advances as well. Technological advance had to occur to keep pace with the discoveries being made and vice versa. Some of these advances are faster computers, better storage of data, and ever-increasing efficiency in sequencing machines. We have sequenced all types of organisms from viruses, bacteria, plants, animals, and people, to even wine and chocolate. The numbers of completely sequenced organisms in each of these categories is relatively small. The number of organisms we have partially sequenced is large and growing. We also sequence the DNA from nonliving organic remains.

At the peak of the Human Genome Project, we were generating DNA sequences at the rate of 1000 nucleotides per second, around the clock. In February of 2013, a gene sequencer came on the market that could sequence 1million nucleotides per second for targeted sequences. That is a 1000 fold increase in 11years. Moreover, they just keep getting faster and faster and cheaper and cheaper. The speed with which this technology is advancing is literally overwhelming.

We have also fairly recently completed the sequencing for hundreds of cancers which have hundreds of mutations because of simple changes in the sequencing of their DNA which makes a gene stop or change functioning.

The most common of the hereditary cancers are breast, ovarian, prostate, and colorectal. These genomes were chosen first in cancer sequencing because of this commonality. We all have similar DNA but it is not exactly the same, we do not get “exactly” the same cancers, even though we are 99.9% genetically identical. It is that elusive one tenth of the genome we look at for our ancestry, and the remainder for indications of disease. Therefore, the sequencing of an individual’s genome can tell us about that person and their ancestry on a genetic level, and grossly simplified, it tells us which gene changes are causing what expressions in the phenotype (body) or other areas of interest such as the biomolecular pathways.

Sequencing identifies problems related to gene coding such as cancers, a myriad of genetic disorders, susceptibilities, and other unobvious interactions at the biomolecular level. The list is literally almost endless. The good news is that it is also getting cheaper to do it… exponentially cheaper. It is calculated that in the next few years, you will be able to have your complete genome sequenced for around a hundred dollars. The magic money goal for quite a few years has been a complete genome sequence for $1000 and we have now achieved that goal. There are some companies doing very tiny parts now for somewhere under $400. However, there are 6 billion bases to the complete genome, so it is a tiny part. There are markers called SNP’s (single nucleotide polymorphisms) these companies use to tell you if you have a genetic predisposition for a certain health issue, such as heart disease, prostate cancer and many others. The bit they examine does not take into account psyche, lifestyle, pollution or external factors because we do not know in most cases, exactly how these factors affect our genes, we know only that they do. This approach then gives a percentage of risk for certain diseases.

We know that pollution damages the vascular endothelium and this damage causes an inflammation that is the precursor to inflammatory atherosclerosis. Demonstrating of course that we do know quite a bit from our current research, but it is so minuscule in comparison to the numbers of genes that it is essentially nothing numerically speaking. This type of information was not on the gene level of investigation until recently and we are not sure what it means on a gene level but we are getting there.

However, what we currently know, along with the information we are gleaning from genomics, can make a huge difference in someone’s quality of life with the appropriate intervention. It will be immeasurably better as the science of genomics continues to improve.

Will we be able to alter the gene, or gene plate, or some other factor in the process to make us more resistant to pollution, or rather the damage it causes on the endothelial level? Yes, we will… and soon.

What These Pursuits Mean – An Overview

On a grand scale, the ability to understand our genome tells us who we are and where we came from. I mean, who we really are. We all carry all our collective human history from the beginning of humankind in our DNA. In addition, we have established that scientific Eve began in East Central Africa approximately 100,000 to 200,000 years ago. She is Humanity’s genetic mother. We have even sequenced the DNA of the Neanderthals and found that a small percentage of the current population carries their genes. Just imagine, not only are we about to change all of medicine and pharmacology and many other sciences, but we will truly know ourselves, for the first time.

At present, we are beginning to be able to find the gene or gene sequence (plate), isolate the coding problem, and understand to some degree how that change in coding has expressed as a disease. It is an intensive and complex process to identify an anomaly after the sequencing has been completed.

You might remember that there are just four nucleobases… guanine (G), adenine (A), thymine (T), and cytosine (C) (see Fig1 above). Ninety Eight percent of your DNA does not code for active proteins. This leaves two percent holding sequenced information from the nucleobases that produce proteins. These proteins manage essentially everything in the body. If the nucleobase is damaged, mutates, was never present, or was wrong in the first place for whatever reason, there can be disease expression because of a malfunctioning protein the gene processes produced, or did not produce when they should have. At this point, we are very limited in what we can do to adjust or repair one of the nucleobases, but that knowledge foundation is growing exponentially as well. In designer pharmacology at present, the focus is trending toward fixing the malfunctioning protein or process that the damaged sequence has created rather than fixing the nucleobase or even the gene plate specifically. Fixing the nucleobase, at the root level, is the ultimate goal however. Some of this is now being done at the embryonic level for the more known or devastating genetic diseases such as Huntington’s Chorea, Cystic Fibrosis, Sickle Cell Anemia and a long list of others.

The genome is sequenced from cells taken from the embryo and examined for known adverse phenotype expression, or in other words, known genetic disease and its bodily expression.

It is being observed, though not clinically proven that treatments for these diseases, based on genomic medicines are far more effective, in some cases even “curative” in the younger patient. This means that being genomically sequenced and treated after the disease has advanced may improve some aspect or quality of life, but in all likelihood will not save you once the damage is done. This is why there are so many advocates for early sequencing in the scientific and medical community. However, as this science advances age may no longer be a factor.

In 2013, the cost for a genome sequence was about $8,000. We have now achieved complete genome sequencing for $1000. The current cost has now become less expensive than many treatments currently in use. In only a few years (approximately 3-5), the cost will be about $100. As the cost falls exponentially and the information grows exponentially this will become the preferred treatment of the very near future, where almost all types of health issues are addressed at the genomic level, with lifestyle and environment not left out, but their effects on the genome much more understood genomically and maybe even more amenable to change or correction.

Though genomics are essential in many diverse fields, the medical field has been given a significant focus because it means curing or controlling the worst diseases that have plagued us for centuries, not to mention changing aging, selecting optimal traits for our children, and even improving the ones in those of us already here. There will come a future time with the use of this science that we will have to ask ourselves “Are we still H. Sapiens Sapiens, or have we become something else?”


The way we view the practice of medicine, diagnostics, and treatment at the present time, is about to change, drastically, and it is already happening. Instead of just treating the disease symptoms, in its outward expression or “phenotype,” we will be treating and curing diseases at the genomic and biomolecular level. We will change the genes themselves and/or their pathways. This has produced a new limb of the medical science tree populated by “omics.” DNA and RNA and the Messenger RNA use many processes to get the coded information from the gene or gene plate to the RNA that can make the protein, which is active in the person or “phenotype.” Examples of these include transcriptomics, proteomics, and metabolomics. These are all representative of accessible pathways of intervention and are becoming or have become specialty medical and scientific fields of their own.

Alterations in these various genomic pathways are being identified as areas of interest or intervention to change the outcome of disease manifestation in the body.

Chemical modifications in these numerous pathways or proteins can be made pharmacologically. Epigenetics studies the effects of environmental factors on the DNA. DNA changes its coding if influenced by outside factors. This means our DNA changes over time for better or worse depending on innumerable internal and external variables.

Thomas P. Cappola, MD, ScM, and Kenneth B. Margulies, MD put it this way:

“For example, emerging data indicate that in-utero exposure to stresses such as starvation can alter DNA methylation patterns of genes involved in growth and metabolism to affect organ development and future cardiovascular risk. Exposures such as tobacco smoke and air pollution may modulate cardiovascular risk in part by inducing epigenetic changes. Animal models have also demonstrated a substantial role for histone modification in cardiac hypertrophy, and drugs that target histone-deacetylases (HDACs) have been considered as a therapeutic strategy for heart failure.” NIH public access document.

What they are saying is that the histone pathway is a target area for use of a designer drug that would be a treatment for heart failure. Think of the number of pathways at the gene level that regulate our bodies and then picture the applications of targeted pharmacotherapy on the outcome of the diseases whose pathways we understand. We will create drugs whose role is so specific that there are not even side effects with which to contend. We also have to consider the amount of drug necessary, which would be minuscule compared to the amounts we currently use. At present, we are essentially treating the whole body, with large doses of chemicals, to control a symptom or symptoms, and our numerous other systems and organs become treated as well with this shotgun approach. This approach opens the door for countless side effects and the need for endless clinical trials for safety, and we know little about the effects of all these chemicals on the DNA. That is all about to change as you can see if you are able to grasp the potential for a new dawn in the age of medicine and pharmacology.

We will be able to identify gene markers that represent Mendelian or “familial” potential for all diseases, including cardiac disease. Heart disease is still the number one killer in the world.

We will also understand the anomalies of rare genetic diseases that affect the cardiopulmonary system, and what will stop their expression through repairing the DNA or one of the pathways at the embryonic level before damage ever appears. Imagine all of the invasive testing this will also eliminate.

Whole branches of medicine such as the Cardiac Cath lab, Surgery, and all manner of invasive techniques, will be relegated to trauma assessment and repair, or be eliminated because they will no longer be needed for diseases. Branches of genomics are already arising for regrowing limbs, organs, and spinal cord repair. The list of pathways and interventions is almost endless as you can see.

The most common areas of interest in cardiology have continued to be researched for the past fifty years because heart disease has been the most common cause of death. Among these are Coronary Artery Disease and Myocardial Infarction, Heart Failure, Arrhythmias, and peripheral and cerebral vascular disease. Ongoing, genome wide association studies continue in these primary areas as well and variants in the genes and gene plates identified or implicated for these vascular diseases. Our knowledge is growing as more and more sequencing is done and comparative patterns across the population are seen expressed in the genomes of the individuals who are sequenced. We have a growing body of knowledge of specific gene patterns accumulating daily from 10,000 or so workers in these genetics fields. In complement, because of electronic medical records and the internet, along with the growth of gene sequencing ability and technology, this knowledge is being shared and the areas of association repeatedly compared and confirmed. This is the path to therapeutic intervention and real cure. If one knows they have a mutation in a gene plate that is associated with early MI, then we can assign a percentage of risk based on the clinical picture of how completely or partially this gene pattern is expressed. Alternatively, in the case of early sequencing, we can intervene in the embryo before the disease is even manifested. We are learning how to do these interventions at an ever-accelerating pace, but there are several libraries of research to be done. The good news is the speed with which we can do this and the ability to store and share the information we acquire.

In this brief article, I have only been able to lightly touch the surface of the rapidly growing fields in genomics and a minuscule amount of what we are seeing now and will be seeing in the very near future in terms of diagnostics and treatment. I hope it has sparked your interest for this amazing and exploding field. I would humbly recommend accessing all the information you can find on genomics and get your head around it. Not only is it changing the world economy, but also our roles, our jobs, and how we deliver health care. It is also changing the way we diagnose, treat, and care for patients and families. Genomics is happening now.


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