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Most everyone has, at one point or another, heard of the Human Genome Project. They probably know that its goal was to map the entire genetic code of humanity and they may even know that it put out its final draft, effectively completing the project, in 2003. What they may not know is how incredibly tedious the process of genetic sequencing really is. Or at least, how tedious it once was.

In the wake of the project’s completion, there has been a general call for faster and more efficient means to perform genetic sequencing. This call has been answered by the birth of a field of study called “Next Generation Sequencing.” This new field is devoted to developing new technologies which facilitate so-called “high throughput” techniques, which allow for high input and high output. This could lead to the sequencing of entire genomes within a single day. What would this new type of high volume analysis mean for research? Well let’s take a look at recent study that makes use of this new field’s advances.

The study looks at the genetic basis for Alzheimer’s Disease by comparing individuals who have minor cognitive impairment (MCI) and significant deterioration of the hippocampus to MCI individuals without hippocampal tissue loss. This type of tissue loss is one of the early biological indicators of Alzheimer’s and can be used as a marker to differentiate cognitive impairment as a result of Alzheimer’s from impairment stemming from other causes. As such, comparing the genomes of those individuals with MCI and tissue loss to those without tissue loss could uncover some of the basic genetic mechanisms that drive the heritability and progression of Alzheimer’s. Without the ability to compare entire genomes, studies like this would be limited in scope to specific genes already suspected of a role in the disease, leaving many potentially unknown genes excluded.

The study, reviewed in the latest issue of Nature Reviews Neurology, found and focused on two gene variants (in a caspase recruitment domain gene family and a polymerase, respectively) which were shared by more than half of those individuals with tissue loss but were not found in any of the other study’s participants. It is suspected that these gene variants are linked to the beginnings of MCI in Alzheimer’s patients and screening for them could help to identify the disease in its earlier, pre-symptomatic stages.

Beyond using new sequencing technology to compare entire genomes, researchers also made use of a new form of statistical analysis. By focusing on the “extreme” trait of tissue loss, the analysis is able to draw a stronger connection of causality between the genetic similarities identified in affected individuals and the loss itself. This is in place of the typical study structure, where individuals with tissue loss would be compared to healthy individuals with similar backgrounds. Traditional studies have a serious blind spot as well, with regards to Alzheimer’s, in that individuals considered “healthy” may in fact have Alzheimer’s but not be presenting any symptoms yet, which would seriously skew any genetic analysis.

“Next Generation Sequencing” introduces a whole new range of approaches in genetics. The ability to quickly sequence an individual’s entire genome opens doors to a holistic view of disease mechanics. This study illustrates how such new technology permits a wider and more complete analysis of pathogenesis as it stems from the genetic code and is defined by heritability.

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