It's probably the most valuable thumb drive I'll ever have, and I couldn't believe I had misplaced it. It contains the blueprint of who I am: My genome. Or at least, all the ways my genes differ from other people's. It turns out, in the grand scheme, we're all very, very similar, genetically: It's in that last one-tenth of 1 percent where we find all of human variation — those things that make us special: athletic abilities not so much in my case , frizzy hair unfortunately for me … and in some cases, a predisposition to disease.
I had set out in August to have my genome sequenced, mainly out of curiosity. There was no problem I was trying to solve or specific answer I was seeking. That puts me in the minority of people who have their genomes sequenced today. As my geneticist, Harvard Medical School's Dr. Robert Green, likes to tell me, I'm among a group of medical pioneers.
This made me feel very cool of course, but having your genome sequenced is a scary thing. What if I learned something dreadful? What if I was destined to get a disease that has no cure? What if I carried mutations that could burden my future children with something awful? Did I really want to know? Obviously, given my hunt for the thumb drive, the answer is yes. Our ability to map our own genes will be a bigger and bigger part of our medical care even in just the next decade.
President Barack Obama has announced a Precision Medicine Initiative to accelerate what's possible using this genetic information. And already, gene sequencing is making major impacts on cancer care, diagnostics and drug development. But it's still controversial how much genome sequencing is necessary, or even very useful on a personal level.
Huge questions loom about cost, privacy and our own abilities to handle this kind of knowledge about ourselves. Because sequencing healthy people isn't a common medical practice, it's not all that easy to do. I participated in a program called Understand Your Genome, provided by sequencing company Illumina.
CNBC paid for the sequencing. Illumina also connected me with Green, my geneticist whose visits were covered by my insurance. In truth, I wasn't sure how I would feel. I hoped my response would be a productive one, a kick in the pants to maximize the time I had, or, later in life, be better prepared for something like Alzheimer's.
But in actuality, it's more likely I was banking on the fact that it was exceedingly unlikely I'd be predestined for something like early-onset Alzheimer's, given how rare it is in general and the fact that it had never turned up in my family. But as I discovered, it was also unlikely I'd learn something particularly useful, or "actionable," as geneticists describe it, a dominant mutation that would predispose me to a treatable cancer or heart disease, for example.
We have two copies of each gene; one from our mom, and one from our dad. A dominant mutation is one where only one copy is needed for its effects to be shown; a recessive one requires two copies. According to Green, only about 1 to 2 percent of people get an "actionable" result. That's in part, I learned, because we're still very much in the early days of interpreting our own genetic information, and in part because our genes don't determine everything about our lives.
It seemed to me those few would certainly feel it was worth it. But, he said, "there is even debate about if you find those few, are you really going to help them, because it hasn't been proven that you can change something and change their outcome. If it feels like genome sequencing raises more questions than it answers, that's due to a yawning gap between what sequencing technology enables us to discover, and how much we actually understand about the information we get back.
Because genome sequencing is so young, we only have a decade and a half of historical data from which to draw conclusions. Our understanding of all the implications of our genetics hasn't caught up yet to the power of sequencing technology.
So while up to 2 percent of people may get a finding they can do something with, 20 percent have some kind of dominant mutation without any sign of disease, Green said.
That means they have a mutation researchers suspect would be tied to disease, but it hasn't actually manifested, and it's unclear if and how it will.
My report would come back with a section titled "Variants of Unknown Significance" — mutations for which there is limited evidence of relevance to disease, but which can't confidently be counted out. I turned out to have two, listed as "suspicious," in terms of whether they were likely to cause disease. Not the most reassuring word to find on your genome sequencing report. But that's a function of how much we know about genes and disease.
The Broad is a nonprofit research institute that is, among other things, one of the world's largest genome-sequencing centers. But since much less DNA is sequenced, whole-exome sequencing is at least currently cheaper than whole-genome sequencing.
Another important driver of the costs associated with generating genome sequences relates to data quality. That quality is heavily dependent upon the average number of times each base in the genome is actually 'read' during the sequencing process. Producing truly high-quality 'finished' sequence by this definition is very expensive; of note, the process of 'sequence finishing' is very labor-intensive and is thus associated with high costs.
In fact, most human genome sequences produced today are 'draft sequences' sometimes above and sometimes below the accuracy defined above. There are thus a number of factors to consider when calculating the costs associated with genome sequencing. There are multiple different types and quality levels of genome sequences, and there can be many steps and activities involved in the process itself. Understanding the true cost of a genome sequence therefore requires knowledge about what was and was not included in calculating that cost e.
In reality, there are often differences in what gets included when estimating genome-sequencing costs in different situations. Below is summary information about: 1 the estimated cost of sequencing the first human genome as part of the HGP; 2 the estimated cost of sequencing a human genome in i. The HGP involved first mapping and then sequencing the human genome. The former was required at the time because there was otherwise no 'framework' for organizing the actual sequencing or the resulting sequence data.
The maps of the human genome served as 'scaffolds' on which to connect individual segments of assembled DNA sequence. These genome-mapping efforts were quite expensive, but were essential at the time for generating an accurate genome sequence. It is difficult to estimate the costs associated with the 'human genome mapping phase' of the HGP, but it was certainly in the many tens of millions of dollars and probably hundreds of millions of dollars.
Once significant human genome sequencing began for the HGP, a 'draft' human genome sequence as described above was produced over a month period from April to June The HGP then proceeded to refine the 'draft' and produce a 'finished' human genome sequence as described above , which was achieved by Of note, generating the final human genome sequence by the HGP also relied on the sequences of small targeted regions of the human genome that were generated before the HGP's main production-sequencing phase; it is impossible to estimate the costs associated with these various other genome-sequencing efforts, but they likely total in the tens of millions of dollars.
The above explanation illustrates the difficulty in coming up with a single, accurate number for the cost of generating that first human genome sequence as part of the HGP. Such a calculation requires a clear delineation about what does and does not get 'counted' in the estimate; further, most of the cost estimates for individual components can only be given as ranges.
The truth is likely somewhere in between. The above estimated cost for generating the first human genome sequence by the HGP should not be confused with the total cost of the HGP. The originally projected cost for the U. But the latter number represents the total U. Further, this amount does not reflect the additional funds for an overlapping set of activities pursued by other countries that participated in the HGP.
As the HGP was nearing completion, genome-sequencing pipelines had stabilized to the point that NHGRI was able to collect fairly reliable cost information from the major sequencing centers funded by the Institute. Since the completion of the HGP and the generation of the first 'reference' human genome sequence, efforts have increasingly shifted to the generation of human genome sequences from individual people.
Thus, the generation of a person's genome sequence is a notably different endeavor than what the HGP did. Not so much. That could be because no one has figured out a sexy marketing campaign for whole genomes yet.
Or, more likely, because there are already much cheaper options on the market that will tell you something but not everything! Today, slightly more than a million people have had their whole genomes sequenced. Compare that to the 17 million estimated to have had their DNA analyzed with direct-to-consumer tests sold by 23andMe and Ancestry.
Genotyping targets short strings of DNA that scientists already know have a strong association with a given trait. So say, for example, scientists discover a new gene that increases your risk of developing brain cancer. Whole genome data on the other hand, once you have it, can be queried with computer algorithms whenever a new genetic discovery gets made. Customers also have to go through a doctor to order the Veritas whole genome test.
But anyone opting for whole genome sequencing right now should be aware that the science is only partially cooked, says Robert C. For one thing, consensus on what different genetic variations mean for disease risks changes over time, as new information comes in.
To get ahead in that regard, Veritas wants to integrate genetic data into the everyday. A quick query could save you some nasty side effects.
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