Source
r/AskReddit•
prionattack

What's the best way to go about getting genetic testing? 23AndMe? Complete Sequencing?

We have been trying to figure out what caused a member of my family's mental retardation - we thought Fragile X, but according to a specialist, if he doesn't have enlarged testicles, then it's not Fragile X. The specialist is testing for XXY/Kleinfelter's syndrome, but that wouldn't explain the fact that this family member has a maternal uncle who seems to have the same condition.

Because this guy is on disability and can't really live on his own (he's reasonably high functioning, but he's over 40 and starting to have trouble - anxiety, arthritis, heart problems, etc.) he's on state medical care, which is only available if he drives an hour to see a primary care doctor, or 4+ hours for any specific test.

The state won't pay for any genetic testing (the test for Fragile X alone is $1700) as he's 40 and it's not likely to change anything, but we're concerned about the possibility of passing these genes on, as well as looking for a way to get him on disability - if we know what the problem is, it's a lot easier to make the case that he can't live on his own - "anxiety" and mental retardation don't cut it, apparently. There are other family members that have severe anxiety problems, muscular control issues, neurological symptoms, etc. but it's not easy to connect the dots without definitive testing - everyone has a few "quirks", after all.

I've been trying to figure out what information 23AndMe gives you, and I've been looking through genome sequencing options, but I'm lost. I have some bioinformatics training, and friends who are quite capable of running sequence alignments, etc. against reference genomes.

What's the best way to proceed here? Is there a DIY way to sequence a genome? Is there a no-bullshit company that will give me the sequences? I need this to be as cheap as possible, as my family will have to pay out of pocket.

TLDR: What's the best way to get a genome sequence to figure out the cause of a family member's mental retardation?

Posted Apr 19, 2012, 3:18 PM UTC

511
abeetzwmoots•

23 & Me is well worth it. They have sales around Xmas & the spring.

2
prionattackOP•

Does it give you specific information about every gene you want to know about? It seemed like the "subscription" service was kinda bull, and that they were just looking for SNPs. My biggest concern is that this isn't a SNP issue, but rather a chromosomal deletion or something like that, where SNPs wouldn't help out at all.

I'm also concerned about the fact that you don't actually get the real data - just the watered down nuggets that 23AndMe wants you to have.

1
sasky_81•

Not worth it in this case, when looking for specific medical information.

1
karlrocks23•

My genetics professor always said that it's not the best idea to get genetically sequenced, because if/when something is found it skyrockets life insurance. There's no DIY way to properly sequence unless you have state of the art equipment and a lotta cash. Not to mention the 3rd level training that's needed to properly carry out the procedure. Companies are going to dominate and make this market enormous in a few years, there's already billions being invested into this technology. (13bn in the human genome project) So if you really want it done, and done properly, you'll have to pay up. But if you know some people you should make use of those options first. :)

2
prionattackOP•

Life insurance isn't a big issue - this guy doesn't have dependents, and there is a bit of family savings to deal with burial costs, etc. I think he may also have some life insurance - his father set things up very well, given that he only had a short time to prepare (he was diagnosed with a heart condition and died 5 years later).

1
sasky_81•

If your family member has a maternal uncle with a similar feature, the suspicion would be some type of X-linked mental retardation. Are there are women on the same side of the family that might have a milder presentation? That is not essential, but it would be more evidence.

What type of specialist ruled out Fragile X? If at all possible, he should see a geneticist. They are skilled at picking up on symptoms / features that might point in a specific direction. Fragile X doesn't fit really well with an older relative having symptoms though - it is possible, but because of a genetic phenomenon known as "anticipation", the condition typically appears in one generation. Nothing is universal, though.

There are genetics labs out there that offer testing for a huge group of genes on the X chromosome that cause mental retardation. This testing is prohibitively expensive ($14,000) or something like that. If you see a geneticist, especially one at a university or teaching hospital, they may be able to get some testing done on a research basis. Not a guarantee, but they deal with this type of situation a lot, and most will try their best to get the appropriate testing done. If it is a deletion / duplication issue with chromosomes - this might get diagnosed with a test for XXY. Chromosomal abnormalities aren't usually treatable, but it does provide an answer.

23 and Me will almost certainly not give you the answer you are looking for. It is not a diagnostic test in any way, shape or form. It is mildly interesting, but for a legitimate medical concern such as this - you would be wasting your money.

2
prionattackOP•

Thank you for the info - that's what I suspected.

It is entirely possible that the affected man's mother has milder symptoms (particularly the crippling anxiety), but it's hard to tell, because she has extreme dementia and has for as long as I've known her. Her brother is the one with the problem as well, which is why I initially thought Fragile X, as the premutation means that females tend to have fewer symptoms.

The doctor they saw (as far as I know, at least) was at a university medical school, and was the head doctor at a fragile X clinic. I don't think she was a geneticist, though. I really don't like second-guessing doctors, but Kleinfelter's syndrome really doesn't fit at all, and so I'm a bit bothered by the mode of inquiry.

I'm not really sure where to go from here, mostly because the testing is soooo expensive that I can't see them ever paying for it, but there are so many questions that could easily be answered by that same testing.

Honestly, if the testing you're talking about is $14K, I'd just as soon pay $5000 and get his entire genome sequenced by Illumina, then run BLAST myself to see what he has.

1
sasky_81•

Do you mind if I ask what your training is?

Does ilumina turn over raw data, or just provide an interpretation? Most clinicians are hesitant to sequence genomes or exomes, simply because it usually doesn't give an answer. You would likely need to sequence several other family members to get an answer, if it is out there.

1
prionattackOP•

I am a statistician, but I was a bioinformatics PhD student for a year before deciding to leave the bio-part behind. I understand how the algorithms work, though. Ilumina seems to give you the sequences without any interpretation as far as I know. I'm pretty sure they're genomes, not exomes, from what little I read online. Fragile X and Kleinfelter's syndrome are both reasonably "big" on the genome scale - there's a sequence of CG repeats (or something like that) that's entirely missing in Fragile X, if I recall correctly, and Kleinfelter's is the presence of an entire extra X chromosome - big stuff.

Obviously any other mutations out there that could cause this would require comparison genomes, which we couldn't easily get from anyone other than one of this guy's siblings (and his descendents) - the others are rather skeptical of science and afraid to find out what kind of mental retardation it is because they don't want to know whether they're at risk of passing it on.

1
sasky_81•

For Fragile X, it is actually an expansion of the CGG repeats, not a deletion. Kelinfelter's is an extra X chromosome. Fragile X might show up on chromosomes. If a doc in a Fragile X clinic didn't think that was likely - they should have a good handle on the finer features of the disease. Both of these might show up with chromosomes, depending on what tests they ordered.

Genetics and genetic testing can be a frustrating endeavour. What is your end goal? Just a diagnosis for peace of mind, or something for better health coverage? Keep in mind that even if you come up with something from the raw data - it is likely going to need to be repeated and interpreted by a board certified geneticist. Most insurance agencies or government bodies aren't going to accept a home diagnosis.

1