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Newspaper articles and the NEJM papers themselves seem to say that genes are not that useful in predicting disease. Are the authors saying that research into the genetics of PD is no longer useful? These papers argue -- rightly, I believe -- that new progress will ultimately require the development of next-generation techniques for peering even deeper into our DNA.
This is how we will capture a more complete picture of how genes contribute to diseases like PD. The papers are essentially the summation of a position that has been growing in popularity among researchers for some time now: The genetic basis of diseases like PD is extremely complex, and current genetic research methods must be augmented with new and more powerful technologies in order to explain the full genetic basis of disease.
But the genetic basis is still unclear for the vast majority of cases. No -- and this is a critical point. The scientists are not concluding that genetics plays no significant role in PD. But I keep hearing about genes that are linked to PD. But finding the specific gene changes that explain disease has not been easy.
It may be helpful if we look at how we reached our current understanding, to help clarify what the new position means. In the earliest days of genetic research, scientists studied rare families where disease was clearly being inherited from one generation to the next. A better method was needed to find genes that might contribute to disease in the general population after all, the vast majority of PD cases are sporadic and do not have a clear pattern of inheritance.
Once identified, the race would be on to clarify and refine which genetic change in that region was the real culprit. GWA studies are a powerful technique, but they have a significant limitation: They can identify only SNPs that are fairly common. But if a disease is ultimately caused by many rare mutations found in relatively small groups of people -- as might be the case in PD -- the approach loses its advantage.
So what are the technologies that we need to focus on now to make new progress? Several of the NEJM authors argue that we need to start thinking about the next wave of technology: A few years ago, it would take many labs and vast amounts of funding to sequence all the DNA letters of just a few individuals.
But the technology is rapidly advancing. That will open the floodgates for new studies of the genetic basis of disease. Can you explain how the combination of new research technologies and novel methods for collecting data from patients may open the floodgates?
With a set of complete DNA sequences from multiple individuals, scientists can compare each letter in the code and find even rare mutations that would have been missed with previous GWA study methods. It is within these rare mutations that many scientists now think the key to understanding complex diseases truly lies.
There is certainly still the risk that even if we go deeper, we may come up empty handed. If that happens, it will likely cause a major shift in our thinking about the causes of PD.
But even with identification of a more complete list of gene changes that contribute to disease, the real work comes in understanding how those changes ultimately lead to disease. Do they alter the levels of proteins in a cell or how they function?
And what other genetic or even environmental factors might impact whether a particular genetic mutation actually causes disease or not? All of this requires not only the ability to look deeper in our DNA, but also to know more about people with PD and what defines their disease.
From the angle of how to convert genetic findings into actual therapies, it is this understanding that is really important. What is The Michael J. But we believe that as technology evolves and becomes more affordable, researchers will continue to identify new genetic variations that play a role in disease onset and progression.
On top of all that, we still have a lot to learn about precisely how specific gene changes lead to disease, which is how you then learn to develop therapies. Ultimately, MJFF believes that genetic research will be key to increasing human understanding of PD, and will play an important role in the development of breakthrough treatments.Microsoft Research Lab - New England Internship.
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