Diagnostic Genomics and You

So I decided to take a little time out from writing assorted papers and my thesis today to write  a little about what I’ve spent the last two or so years of my life working on, which is diagnostic genomics. To be honest, this is going to be ranty and relatively low on scientific content, since I’m still working on publishing a lot of material.


So, what is diagnostic genomics? At its core, it’s sequencing large chunks of your DNA all at once, and the assorted interpretation of those findings.

Genetic diseases can manifest in a huge number of ways, and the testing panel that I’ve taken the lead in working up focuses on genetic diseases affecting the heart, central and peripheral nervous systems, and the skeletal muscles in the body. Much more common genetic diseases are Down’s Syndrome, caused by having 3 copies of chromosome 21 (humans have 22 pairs of autosomes, or non-sex chromosomes, plus the X and Y chromosomes, which determine what sex you are), or cystic fibrosis, caused by mutations within the CFTR gene. These two diseases are at the very least, commonly and easily tested for – often while a child is still in the womb.

Hopefully, no-one reading this is, afflicted with, or will have children affected by a genetic disorder. If you are affected, or do have a child affected with a genetic disease, I feel for you, I really do. The diseases I work with can be particularly nasty, often resulting in premature death.

So, you might be asking, what happens if someone is affected by one of these nasty diseases? They’d obviously want a genetic diagnosis, right? Ideally, this is what would happen in every case. Unfortunately, this isn’t so. There are more than 20,000 genes in the human genome, and even though we sequenced the genome fully 14 years ago, we still haven’t reached a point where we can comfortably say, yes, we know what every gene in the body does, or at least can tell which ones are essential to proper human functionality. But don’t fret; we’re working on getting the technology to do this! In fact, I would think that we’re most of the way there.


That’s a bit tangential, though. Let’s focus on how this affects the patients and use a hypothetical example.

Our hypothetical patient is the child of two normal parents with no previous history of genetic disease. They presented at birth with muscle hypotonia (muscle weakness), moderate respiratory insufficiency at birth, and joint contractures (a muscle,  joint, tendon, ligament, or skin deformity that limits movement). A huge number of diseases, genetic and non-genetic can display these symptoms, both of muscle and nerve. From there the clinician taking care of this patient usually will request further tests; for example, a muscle biopsy to see whether there are any pathological features that point to a particular disease.

Of course, the number of tests done will be much more exhaustive than this, but for the sake of expedience, let’s say that the pathological findings from the muscle biopsy point to a disease of one of three genes – the ryanodine receptor (RYR1), or selenoprotein N1 (SEPN1).

Of these two genes, only SEPN1 is easily and cheaply screened. The cost of sequencing RYR1 completely using traditional diagnostic sequencing methods will be at a conservative minimum estimate: $2,160 for RYR1. If a mutation is not found in the SEPN1 gene, it is unlikely that a clinician will recommend the sequencing of RYR1 in its entirety. Even if it is sequenced, there remains the possibility that a mutation won’t be found in it, as the full genetic spectrum of muscle diseases has not been identified yet.

What happens then? Our patient and their family, despite the best efforts of their clinician is left with a diagnosis of what disease they have, but no genetic diagnosis. What if the family wants to have another child? There is no way that they can screen the child in the womb, or even pre-implantation, if they chose to go the IVF route.


This is where diagnostic genomics steps up to the plate.

What it does is leverage the sequencing power of so-called “next generation sequencing” technologies in order to screen a large number of genes at once, at a cost orders of magnitude below traditional methods.

We can sequence the coding sequence of every single gene in the body for less than $1000 nowadays, and this is a huge achievement. The technology is there, but the expertise in interpreting the results has yet to fully catch up to the availability and speed of the machines. Other tests that only sequence a select number of genes where mutations are known to cause disease can be even cheaper. This sort of test is what I’ve been working on.


Let’s go back to our patient. Their clinician has informed them of a new test that can be performed for as little as $500, and will screen almost every known neuromuscular and neurogenetic disease gene. What’s even better is the fact that a positive or negative result can be delivered within two weeks.

THAT, right there is the power of diagnostic genomics. It is the power to screen hundreds of known disease genes at a time and deliver timely, accurate results to large groups of patients. It’s a paradigm shift in the field of genetic testing, and here is where my rant starts.


I don’t care if my panel isn’t the one that’s used. I don’t care if it’s superseded by a better technology or method, as long as most people know of it, and have access to it. I know of three, maybe four diagnostic genetic laboratories in Australia that are doing this kind of testing.


This is not new technology. It has been proven to be accurate and reliable, with software available that makes interpreting the results much easier than it was before. What’s more, results are easily confirmed through other, previously accredited methods. There is a huge amount of inertia in the clinical community that is reluctant to embrace new technologies, even with adequate safeguards against false diagnosis in place. This needs to change, for the sake of the patients. Embrace the genomic testing revolution.

Stay angry my friends.

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