We all know we’re going to die eventually.

Sorry. This is gonna be a cheery one.

But sometimes, in rare and devastating  cases, death comes out of nowhere – out of a clear blue sky, with no warning,  in people who seemed totally healthy. Autopsies are a go-to method for  puzzling out unexplained causes of death, but they don’t always clear up the big  picture of what happened in the body as much as we’d like. Fortunately, with modern scientific  tools, we can zoom in closer, with genetic sequencing to search  for clues about what happened.

Yes, you heard me right,  getting your DNA sequenced can still be useful after you’ve passed away. To help us along in this video, we’ll refer to a fictional example  patient who we’ll call Jay Doe, to visualize when and why  we might want to do this. [intro What happens when we die? To quote Keanu Reeves, the ones who love us will miss us.

They also may want to know what happened. Forensic autopsies are ordered in the case of  suspicious circumstances or a suspected crime, whereas medical autopsies help  to clarify the cause of death in order to give the family closure. Depending on the reason for the autopsy, the procedure can include x-rays, incisions, and taking samples of the organs, all to look for any signs  of what caused the death.

Unfortunately, not every autopsy  ends up with a neat explanation. Our example individual, Jay Doe, was an adult under 45 with no known health risks. There was no forensic autopsy, since there was no reason to suspect foul play.

A medical autopsy offered no  clear explanation for their death. Procedures like this that conclude  without finding a clear cause of death are classified as sudden  unexplained deaths, or SUDs. SUD is an umbrella term that covers  various causes of unexpected mortality, including Sudden Unexpected Infant  Death and Sudden Cardiac Deaths.

And In case your health anxiety  needs to hear it, as is mine, these are very rare, affecting around  11,000 people in the United States under 45 every year. That’s out of a population of  nearly 200 million people under 45. Even though we’ve been doing  autopsies for thousands of years, the result can still end up inconclusive.

And for autopsies done on  young people with sudden death, up to a third might end up  without a definitive result. But around the turn of the 21st century, genetic sequencing gave researchers a new angle t o work on explaining those  sudden, unexplained deaths. Enter the molecular autopsy.

This procedure can give valuable  information to not just medical examiners, but also regular folks like the Doe family. We’ll learn what that is right  after this quick message! This SciShow video is supported by Brilliant, the online learning platform for math, science, and engineering students from  grade 5 through undergrad.

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Koji never gives away the answer. Instead, Koji will ask questions and guide  students to find the answer themselves. To get started with Brilliant’s tutor for  free, click the link below or scan the QR code.

You can upgrade to Premium to unlock all courses. And right now, SciShow viewers can  save 20% off an annual subscription at brilliant.org/scishow DNA sequencing has been a tool of  molecular biologists since the 1970s, but it wasn’t until 1999 that scientists  started using it in post-mortem investigations. These investigations, called postmortem genetic tests, or informally, molecular autopsies, involve sequencing the DNA of the deceased to look   for genetic clues that could  point to the cause of death.

More specifically, scientists use a  technique called whole exome sequencing to read protein-coding regions of the DNA from the deceased person’s  blood and tissue samples. The scientists then look through the genetic  code and categorize any mutations they find based on how likely that mutation  is to have been the cause of death. Molecular autopsies are done  more often on young people, as their cause of death is  more likely to be unclear.

Especially in the case of  certain sudden cardiac deaths, the death may be the first and  only sign of a rare mutation. For example, long QT syndrome  happens when the heart takes   too long to reset itself in between beats, which leads to a super fast, irregular heartbeat. Short QT syndrome is the opposite,  where the reset time is too short.

These conditions can lead to an arrhythmia, where your heartbeat is irregular or inconsistent. This can be harmless, but it  can also be life-threatening, and sometimes people don't show  any symptoms until too late. Plus, while both of these are rare diseases, short QT is so rare that it was only  first described in the year 2000, and we’re not totally sure how  many people actually have it.

So if someone passed away because of short QT, doctors and medical examiners  might not think to look for it. Fortunately, we do know some of the  mutations that cause those problems, which we can find by genetic sequencing. Molecular autopsies have been especially  helpful in identifying genetic defects that affect the electrical  signalling in the heart, including long and short QT syndromes, because electrical defects can’t  be seen in a physical examination.

There are five genes associated with  long QT that researchers can look for, with about 60 locations in the genome  to scope out during a molecular autopsy. And some of those genes may also  be involved in short QT syndrome. So let’s say that Jay Doe’s  molecular autopsy revealed that they had a mutation  associated with long QT syndrome.

There’s plenty of reason why we’d  want to know that, even after death. While these autopsies unfortunately  cannot change the fate of the deceased, identifying those mutations could  help other people get checked and informed of any possible prevention options, including living members of the Doe family. By finding out if they have any of the  mutations associated with sudden death, people can be advised to avoid certain triggers and be given preemptive treatments like  medications or an implanted heart monitor.

So, given all of this life-saving information  that we can get from a molecular autopsy, it might seem odd that this procedure isn’t  performed universally in cases of SUD. Well, first of all, genetics  can’t always tell the whole story. As always, the more data, the better, and with this relatively new method, there is still plenty we don’t know.

One 2023 review reported that molecular autopsies find a possible cause of  death just 25% of the time. That may at least partially  be because diagnostic tools   for molecular autopsies aren’t fully standardized. Even if the autopsy finds a  promising explanatory mutation, it’s important to confirm that the  variant would actually cause the death.

There are some instances where clinical guidelines recommend a molecular autopsy, especially in cardiac cases, but not having a standardized procedure  is actually a pretty big problem. Science is all about being  able to repeat your findings, so having a common method  across the field is crucial. And because it’s not standard, not every medical examiner is collecting and preserving the blood and tissue samples that you need to even perform the  molecular autopsy in the first place.

Plus, even though molecular autopsies  are becoming more affordable, especially with genetic  sequencing getting ever-cheaper, it’s still not nothing – at least a few hundred US  dollars, up to a few thousand. Medicare stopped paying for autopsies in 1986, and doctors don’t really want to ask a  grieving family to pay for an autopsy simply in the interest of the greater scientific good. Finally, we have to consider the potential  harms of conducting a molecular autopsy, especially for the surviving family members.

Medical examiners aren’t always  required to obtain informed consent from the family of the deceased. And one reason this is a problem is  that autopsy reports can be made public, which could put the family’s privacy at  risk by revealing their genetic information. they should be communicated to the immediate  family of the deceased thoughtfully and with actionable follow-up. In the case of negative results, the family should be informed of the  limits we’ve already talked about – that molecular autopsy can’t  always find the answer.

And for positive results, immediate family members should be given access to genetic counseling, where a healthcare professional can  walk them through their personal risk, how to manage it physically and emotionally, and options about informing  the rest of the family. In the case of heart conditions  like long QT syndrome, this could look like regular cardiac check-ups, prescribing certain medications,  or lifestyle changes. A genetic counselor can also help you decide if   you want to get genetic testing  for certain mutations yourself.

If you’re worried, talk to your doctor and they can help you figure out what risk  management plan would make the most sense for you. With more research, we can work towards understanding the  causes of sudden unexplained deaths. Advances in post-mortem gene sequencing can help out regular folks like the Doe family, and even possibly prevent sudden deaths  like Jay Doe’s in the first place. [ OUTRO ]