Could Whole Genome Sequencing (WGS) help me?

[jamienoble]

I have been sick for many many years, i have had a medical investigation going on for 9 years and pretty much all my tests has been normal, at least nothing that can explain my symptoms. I strongly believe that i was born with a disease and then my symptoms became fully developed around the age of 13 or 14. its either that or i got my disease / infection when i was very young and it has stayed in my body ever since and cant be found, that just seems very unlikely to me.

10 years ago i got cured for 6 months when i took Roaccutan (Isotretinoin) against accne. I took Roaccutan for 7 months, a couple of months after i stopped taking it all my symptoms went away and then gradually came back again 6 months later (acne disappeared tho).

I haven't found anyone anywhere who has experienced anything similar, Isotretinoin is known for its negative side effects and can pretty much only cure skin problems and cancer.

 

I have a curable disease that temporarily can be cured by Isotretinoin and it affects the brain, skin colour, body odour, hair and fatigue, that's all i know.

I recently heard about Whole Genome Sequencing (WGS) and its something i feel like i want to do. I have talked to two Swedish gene scientist but they are kinda sceptical that i will find anything of value doing such test.
They told me it could work if i knew what type of disease i was looking for but not in my case. That there are about 50 000 mutations in all of us and several thousands of them can be connected to my problem.

What do you think? Could i find any clue by doing a WGS analysis? What can i do with the data myself? What should i look for?

 

If i decide to do this i would probably do it through this lab: https://www.scienceexchange.com/labs/clinical-microarray-core-ucla 3500 dollar with data analysis

Thanks for the help..

Edited November 23, 2015 by jamienoble

[CharonY]

For actual medical advice you should take to physicians. What I can tell you is that our biological knowledge is currently far too limited to derive diagnostic information from whole genome sequencing. I.e. the only information would be based on known targets which can be done cheaper and faster with conventional tests. So the information you have is quite accurate.

 

There is work on omics-related technologies (such as genome sequencing, proteome analyses, transcriptome analyses etc.) which are aimed to identify physiological traits, including diseases based on this complex data. The problem is that we basically learned that it is much tougher to find a link between molecular information and the physiological manifestation (i.e. phenotype) than originally anticipated. To put that into perspective: in E coli, a simple and arguably the best investigated organism we have no clue what about 25% of the genome is doing. Moreover, from the rest roughly half we only have rough idea but often insufficient experimental evidence. So you may understand that if that is the case, we are having a much harder time with multi-cellular, complex organisms.

[DevilSolution]

Sorry what is your disease and symptoms?

 

There's a big problem in genetics at the moment in so much as we don't fully understand junk DNA. The approximation of genes in our DNA is about 20,000 which is approximately 1 to 1.5% of our entire DNA. Now of the non-coding DNA we know (i think) around 20% of junk DNA is made from old viruses embedding themselves into our code for their own survival purposes. So essentially the remaining 78% or so DNA is neither a gene or legacy DNA. So what is it?

 

Most agree that about 2% is mRNA which are the messenger RNA's that essentially tell ribosomes which proteins to make. Then we have micro RNA which we believe act as triggers for the gene expressions themselves, in fact acting as multi-switch operators for genes, controlling the ribosomes to another extent by telling it how much of a protein to build, when to start building, how long this protein should be etc.....This class of RNA is predicted to be atleast the size of Gene DNA itself if not more.

 

(this class of RNA i think may relate to your condition specifically, if this miRNA is misfiring, it could be mis-triggering gene-expressions, extending proteins or not making them at all)....

 

Finally you get interference RNA, i dont know or understand a great deal about interference RNA other than it acts in a similar fashion to miRNA in that it can control the size of protein creation, I think this type of RNA is called RNAi and when it's used on or in a sequence its siRNA, i'm guessing this is a sub category of miRNA but again i dont really know.

 

 

So to summarize, there may be a explicit gene expression of a disease in your DNA, there could be a problem with a specific mRNA not ending with the right codons or such or there could be a malfunctioning miRNA or set of miRNA (such as siRNA).

 

Unfortunately not a great deal is known about the functionality of miRNA within the bigger picture of the DNA, so this would be hard to identify, especially any misconfiguration of such a complex system.

 

 

 

Also i dont know what process takes place that give ribosomes the soup of amino acids (from food to cell) but there could be an essential missing link in the chain that determains the levels of amino acids in the ribosomes that are trying to express that particular gene.

 

Do you know what biochemical process this chemical "Isotretinoin" has on the cellular level?

 

WGS will be able to tell you whether the disease was dormant or not, im not sure it will tell you whether this chemical triggered the disease or not.

 

 

 

 

NEWS JUST COMING IN, your not the only one!

 

http://www.bbc.co.uk/news/uk-wales-34904556

 

If you do a google search quite a few recent results come up. This actually came on TV not long after i wrote my reply.

 

 

Have you spoken to the company that sells this "Roaccutan" as an acne cure, by the looks your not alone. They will probably have to pull it from the shelves.

Edited November 23, 2015 by DevilSolution

[jamienoble]

My symptoms are: Mental Problems (thinking feels blocked, concentration problems, often forgets words and sentences, nervousness, bad memory, easily irritated), fatigue, pale and ill looking skin colour, bad body and urine odour, dry and lifeless hair.

Just to clarify, i was cured by taking Roaccutan (isotretinoin) not the other way around, all my symptoms went away for 6 months until they gradually came back again around the same time.
It may sound weird but i didn't know i was sick until this happened, i was young and i went to school and felt bad everyday but i never cared. When this happened i realized i have lived all my life as a sick person which i thought was normal. This wasn't because of a depression or hallucination, going from sick to healthy to sick again was extremely clear to me, especially with physical changes happening (skin colour, body odour, hair).

I need to find a clue, another piece of the puzzle to find this disease and that's why i wanted to do this Whole Genome Sequencing.


What would you do in my position? If you knew for 100% you had a curable disease in your body but the medical investigation is going nowhere? Are there any other genetic related tests that i could do instead of WGS?

Thanks for the help..

[CharonY]

The only way forward is to talk to more medical specialists and hope to find one who can do a proper diagnosis. A message board is not the way to obtain medical advice, especially for a potentially undiagnosed condition. People here will make random guesses that, given lack of training and (luckily) access to your medical records will unlikely be relevant.

 

The only thing I can tell you with any amount of certainty is that in its current state genome analysis are not terribly useful as diagnostic tools yet.

[swansont]

!

Moderator Note

 

What CharonY said.

 

This is not the place to get anything resembling a medical diagnosis. Go to a healthcare professional.

 

If you can formulate questions about specific biological/chemical processes that do not involve a diagnosis of any sort, you are free to ask such questions. Participants should also refrain from offering anything resembling a diagnosis.

 

[jamienoble]

Im not asking for medical diagnosis, im asking for potential genetic tests that could help me to find whatever is causing my problems.

What do you think about this genetic test? http://www.illumina.com/content/dam/illumina-marketing/documents/clinical/TransGenBroch_UndIns_1111314.pdf

"TruGenome Undiagnosed Disease Test is a medical test intended to aid in the diagnosis of inherited diseases of single-gene etiology."

 

So if i don't have an "inherited diseases of single-gene etiology" this test would be useless to me?

[hypervalent_iodine]

Going on a fishing expedition is not going to help you, not to mention being prohibitively expensive. The website you linked is a supplier page for the kits needed to perform the test. You would still need to find someone that has the necessary machine and is willing to run your samples. Then someone to handle the data and interpret the results. And for what? You have no idea what you're looking for and chances are, it's not going to come back with anything useful.

 

Speak to your doctor. Be insistent that they help you figure it out. Spending thousands upon thousands of dollars on genome sequencing is a waste of both your time and your money.