In the age of personalised precision medicine, DNA sequencing has greatly accelerated medical research and discovery.

Today, DNA sequencing has become a major player in many areas of research in fields such as medicine, forensic and anthropology. Here are just a few ways DNA sequencing has benefited medical research.

1. Identifying repetitive DNA defects

One of the marvels of DNA sequencing lies in its ability to detect exceedingly rare and unknown medical conditions. One such case is that of Rick Ramon who was diagnosed with a benign tumour located in the top-left chamber of his heart.

Despite several surgeries, the tumour kept recurring and had spread to his pituitary gland, adrenal glands and thyroid glands. Ramon was suspected of having symptoms of Carney complex, a genetic condition caused by mutations in a gene called PRKAR1A.

Yet, standard DNA tests did not reveal any defects in his PRKAR1A gene despite sharing the clinical symptoms of Carney complex.

Researchers then decided to employ whole genome sequencing, which identifies much longer DNA reads.

Where older methods were only be able to identify up to 100 base pairs, long-read allowed for researchers to identify up to 7,000 to 8,000 base pairs.

For the first time, researchers had used the technique to diagnose a patient, and successfully identified the complex mutation in Ramon’s PRKAR1A gene confirming his diagnosis of Carney complex, a condition with fewer than 750 individuals known.

“People use short reads because they’re cheaper,” said Dr. Eric Green, director of the National Human Genome Research Institute at the National Institutes of Health.

“If long-read technology gets advanced enough and cheap enough, people would switch.”

While the confirmation of the diagnosis does not change Ramon’s treatment, it does shed light on the nature on his condition. And it is not just Ramon who will see the benefits of long-read DNA sequencing as this new technique opens the doors to the identification of many possibly unknown diseases. 

2. Detecting an elusive brain parasite

When doctors at the Zuckerberg San Francisco General Hospital could not figure out what was wrong with the 29-year-old Nicaraguan man that had come in for repeated visits – it was DNA sequencing which came to the rescue.

Despite multiple visits to the emergency department and numerous prescriptions amounting to USD580,000 – the patient who had come in suffering from splitting headaches, double vision and ringing in his ears, had not gotten any better.

When an initial diagnosis of encephalitis and tuberculosis did not see any treatment results, the team decided to refer the patient to S.F. General, which employed an experimental test called ‘metagenomic testing’.

By carrying out a DNA sequencing of the patient’s cerebrospinal fluid, the team was able to cast an extremely wide net to detect any known virus, bacteria, parasites and even fungi. With the test complete, the results showed that there were traces of tapeworm DNA – hence, shedding light on the entire situation.

While fairly common in Nicaragua, tapeworm infection of the brain is normally undetectable via traditional means. Fortunately, anti-worm drugs worked very well and the patient ended up with a complete recovery.

S.F. General’s metagenomics studies are just one of the ways that DNA sequencing is aiding in public health namely in identifying unknown diseases. Currently, the goal is to make the test more reliable, affordable and widespread. There are also future plans to expand the testing to include infection of the lungs and bloodstream.

3. Discovering risk genes for Tourette Syndrome

Recently, an international team of researchers successfully identified the first definitive risk genes for Tourette Syndrome.

Previously, Tourette has been often associated with a genetic link owing to the familial link present with the syndrome. Nevertheless, no clear genetic link has been discovered, until now.

Unlike other risk genes which lie in a single variation, Tourette Syndrome consists of various short sections of gene variations which are repeated throughout the chain.

“These variations may involve a large part of the DNA sequence and may even include whole genes. We have only very recently begun to understand how copy number variation may relate to disease,” says Peristera Paschou, Purdue University associate biology professor.

“In the case of this research on Tourette Syndrome, we scanned the entire genome… and through physical analysis, we were able to identify where this variation lies,” she added.

Dr. Jeremiah Scharf, co-senior author of the report, said, “We rarely find variants that are associated at such a high level. This is why this is such a big breakthrough.”

The success of the Tourette Syndrome study will serve to benefit not just itself; but, other studies by extension through the understanding of genetic risks not being confined to single gene disorder. MIMS

Read more:
Revisiting the Human Genome Project and other health studies for a more holistic view of genetic diseases
Canadian doctors identify new genetic disorder in children
Personalised medicine: Tailored to fit each person’s genes