Predicting Disease

I’ve talked a couple of times on here about next generation sequencing technologies and the potential they hold in diagnostic medicine. Each time though, I’ve tried to stress the issues and obstacles which still face the emerging field and the possibilities it presents. Well a new study coming out of Texas, published this week in The Proceedings of the National Academy of Sciences, is looking at how these obstacles can be addressed to get potential benefits to the patients.

The study combined whole exome sequencing with patients’ medical histories, a three generation pedigree, and genetic counseling and education practices to both evaluate risk for a wide variety of diseases and give patients the information they would need to act on their results. Out of their 81 patients, the researchers linked a personal history of disease with genes known to cause those diseases in 18 patients, and were able to answer questions about family histories of illness and the risks they present for a number of participants. Any participants whose results showed risk for disease were advised to tell their doctor and have the results confirmed with a CLIA (Clinical Laboratory Improvement Amendments) approved lab.

A readout showing the sequence of part of an individual’s genome. (Source:

While the study was able to illustrate how these new sequencing technologies can be brought into a clinical setting and pass real benefits on to patients, it also highlighted a number of deficiencies in the current system. According to the paper, the biggest issue that needs to be addressed is our knowledge of the genetics of disease and the accuracy of our databases. While a good number of genomes have been sequenced, many of the databases that contain them are not accessible to the public. As a result, it is more difficult to effectively screen for all dangerous gene variants, since our number of known variants is inherently limited. At the same time, those databases that researchers actually can access are not 100% accurate. Errors are fairly common in fact, since some sequencing techniques are less thorough than others, which leads to weaker databases. According to the study though, their results are still fairly strong despite the weaknesses of those databases, since they were able to integrate personal and family medical history into their analysis. So by combining a number of different approaches to predicting disease, the group was able to somewhat overcome the pitfalls of genetic sequencing.

The study is also testing out another emerging field with its results: adult genetic screening. Prenatal screening is now accepted practice for a number of common and potentially dangerous genetic diseases and disorders, but these tests are disease specific, not genome-wide. For adult-onset disease though, there is a much wider pool of diseases and thus a much higher number of genes that need to be examined to evaluate risk. This means whole genome sequencing is much more convenient, but could present new ethical quandaries. For example, the paper talks about finding an APO-E gene, which is linked to Alzheimer’s. Learning that you have this gene and thus may develop Alzheimer’s does not lend you new prevention alternatives or treatments. It is, as the paper calls it, non-actionable. So is it ethical to tell a patient they may get a disease they can do nothing about when it is discovered in a routine disease screen? It is worth noting that only 3% of the studies participants were unsure about getting this kind of information, the rest agreeing to accept information that may not actually help them, but only inform them.

I think it’s interesting that such a large percentage of participants decided to take that information. Personally, I think it is because the types of people who are drawn to this emerging field are not necessarily people who are looking to cure a disease or even hold at bay the inevitable decline into illness or senility. They are people who want answers. They want to understand what is happening to them and why, to find some explanation for their own disease or their family’s disease, regardless of whether or not the information can save their life. As these sequencing technologies become more and more refined, and studies like this work to incorporate them into everyday treatment, those explanations will become more accessible and understandable, which will hopefully help a lot of people face their disease more confidently.

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