Forum:What Next After Snp Identification

Question

[AP]

Hi everyone,

I have recently enrolled in PhD in bio-medical genomics. I have understood that by doing NGS on large scale of disease samples we can predict the putative disease causing SNPs or genes responsible. But I am not getting whats next. After the identification how will it help in future disease curing? What is the next step once we find the gene/SNP responsible? What is the end point of these studies? It will be nice if someone can explain me this.

[Alex Paciorkowski]

This is a very general question, probably better as a forum discussion.

[swbarnes2]

Not exactly...you only hope that you can connect specific SNPs to health outcomes and/or responsiveness to possible treatments. The reality of that kind of study is that lots of what people find and report will fail to be validated in larger studies.

Answer 1

[Martin Dinov]

Pharmacogenomics is one useful side of using results from things like NGS and GWAS. This refers to using genetic markers to predict an organism's response to a drug. We identify one or more SNPs or alleles as being statistically correlated with a given phenotype - in the case of pharmacogenomics, this is some biological response/measurement that corresponds to some drug treatment. This is useful in more accurately gauging the amount of a drug that a person is likely to need for an effective dose. But many (most?) GWAS for example look at SNP-to-disease association. In that case, if we find that some SNPs are very strongly associated, we first ask look at where those SNPs are. If they are in exonic regions, we might then look at whether the respective genes have known gene-gene (or protein-protein) interactions. Gene annotations also help, as they can tell us additional already-known details about the SNP or gene. Using annotations and known gene-gene (or P-P) interactions, we can additionally supplement network analysis. Such network analysis might reveal that some SNP (which is in an otherwise seemingly uninteresting region) is actually acting as an enhancer of some important gene elsewhere, perhaps in a multi-step metabolic pathway. In short, we can look at and analyze the results from NGS (or GWAS) in any number of ways, with the ultimate goal of finding new mechanistic explanations behind the phenotype we're interested in. Without the pointers and hints that such studies give us, we often don't know what to look at and what kind of drugs to make to treat diseases.

[AP]

Thanks Martin for the explanation

Answer 2

[Pavel Senin]

I think that they call that Pharmacogenomics - the study of ways the genetic makeup affects one's response to drugs and how to tailor those.

[AP]

Thanks for the comment and the link.

Answer 3

[Emily]

I'm slightly concerned that you're a new PhD student and there isn't someone in your group who you can discuss this with. Really, your supervisor should be talking to you about your long-term goals and the purpose of your research.

Try and speak to your supervisor as much as you can. Pop into the office whenever you have questions about this kind of thing. If s/he is away a lot, find out when s/he is in the office and book appointments. Do you have a senior PhD student / post-doc / research assistant in your group who you can talk to about these things day-to-day? If your supervisor won't help you, and you don't have another group member to help you, you should speak to your graduate studies committee because it is a serious problem if you're not getting the proper support.

I think it's great that you've found BioStar at this stage of your career and that you'll be able to use us as a sounding board. We're all glad to help. But your supervisor really ought to be there for you.

[Pavel Senin]

It depends on the school policy, it may be too early to pick an adviser.

[Emily]

What about a personal tutor or director of studies? Whatever the policy at your University - you should not be starting out on your PhD without somebody with whom you can discuss this stuff.

[Pavel Senin]

I do see your point, but sometimes it may be not even necessary. For example, when I was studying math, we went through a lot of complex things but never discussed Banach's space connection to a real life. OP can clarify the situation, but I wouldn't blame the school.

[Emily]

It's not about what you study in lectures (you can't cover everything), it's about having somebody available to discuss things with. If the University doesn't have this, they are failing their students.

[AP]

Dear Pavel and Emily,

I am sorry for being late in reply. I am still undergoing lab rotation, not yet finalized which lab I will join. Thats why I ask my query into this forum.

Answer 4

[Ying W]

In contrast to the Pharmacogenomics answers already given, another area of research from SNPs is on understanding the mechanism of what is deregulated. With pharmacogenomics. one uses SNP markers and patient response to drugs to give insight into which drugs work better for certain patients. One could instead focus on what the SNP is doing to the cells to gain insight into how the disease is occurring. For SNPs that are coding and create a missense or nonsense mutation, it is obvious that the gene with the SNP is affected, however, for SNPs in non-coding regions, these SNPs could be affecting enhancers and identifying downstream affected genes is more complicated (need to use techniques like 3c). Ideally, one could link the gene(s) affected by the SNPs to some pathway and show that deregulation of this pathway is what causes/contributes to the disease and thus future drug screens/studies should focus on repairing the pathway. This approach is more of a mechanistic or basic research approach.