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Big Data App to Explore Genomes for Clinical Relevance, Rare Variants, Drug Response, etc (Free)

nyanko_the_sane

Because everyday is Caturday...
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Hi @kday,

Thanks for all your hard work on this. I have a suggestion.

Perhaps you can add a media print style for the id "tabs-container" adding display: none. This would prevent the navigation tabs from showing on the printed and PDF output.

CSS:
@media print {
      #tabs-container { display: none }
}
 
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@nanonug. That report is completely wrong. I believe the issue is that you uploaded a file generated by 23andMe many years ago using a different genome assembly.

Can you confirm the date in your file by unzipping it and sending me the header of the file. Because if so, you need to download an updated file at https://you.23andme.com/tools/data/download/

I also need to make an error for very old files with a link to download an updated version.
My data is from 2012 (23andme) and I got a bunch of mitochondrial stuff too...similar to nanonugs. Will get a hold of an updated file later and try again. :) *Phew*.
 

kday

Senior Member
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I believe all those MT-DNA SNPs are pretty common. I don't have mtDNA frequencies yet next to mtDNA variants, but I checked a frequency file I have.

As far as the other SNP and your mom, I don't know why. It could be misgenotyped. And things aren't always inherited in the ways you would expect. Nevertheless, this SNP appears to be benign.
 
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I have noticed that all the mitochondrial DNA mutations I have looked up all say "novel" and therefore don't have an associated RS number or population frequency even though many people on this site share the mutation, why would this be?
Are all the tools available to enter my raw data into require payment to look up these genes?
 

wigglethemouse

Senior Member
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I have noticed that all the mitochondrial DNA mutations I have looked up all say "novel" and therefore don't have an associated RS number or population frequency even though many people on this site share the mutation, why would this be?
Do you have 23andMe data? Did you download a latest data file from 23andMe - they get updated from time to time and some errors get corrected. 23andMe has quite a few errors, which the tool in this thread seems to correct for.
 

Moof

Senior Member
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Location
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I have noticed that all the mitochondrial DNA mutations I have looked up all say "novel" and therefore don't have an associated RS number or population frequency even though many people on this site share the mutation, why would this be?
My (limited) understanding is that there are many variants which haven't been characterised yet, as working out whether a given variant has consequences for mitochondrial function is quite challenging. If this is correct (@kday?) there's no point paying for analyses, as there's as yet no reliable information to find.
 
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I have 23andme data and updated within the past couple of weeks. Most of the mitochondria positions have a number starting with an I instead of rs so not certain how to look those up. And there are so many it would be difficult to look them up individually. Some of the mutations are even listed at 6% frequency population but still listed as novel, this kind of seems peculiar to me. I wonder why they make it so difficult to look at these specific genes.
 

wigglethemouse

Senior Member
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I have 23andme data and updated within the past couple of weeks. Most of the mitochondria positions have a number starting with an I instead of rs so not certain how to look those up. And there are so many it would be difficult to look them up individually. Some of the mutations are even listed at 6% frequency population but still listed as novel, this kind of seems peculiar to me. I wonder why they make it so difficult to look at these specific genes.
If you provide some specific examples and links to the data such as 6% frequency you quote maybe some folks can offer advice. Not all variations are damaging or known to cause disease.

Did @kday's tool in the original post in this thread also pick up the variation? There are some posts where @nanonug also had mtDNA problems that @kday commented on..

If you really want to dig further into your mtDNA check out the book on this thread written by a user here
https://forums.phoenixrising.me/threads/my-e-book-“tracing-chronic-fatigue-syndrome-to-mtdna”-will-be-free-wednesday-and-thursday-on-amazon.62359/
 
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Here are some mitochondrial positions that are listed as in the 1 to 10 percentage frequency range but we're listed as novel and I tried to look them up.

ChrM:12501
ChrM:13708
ChrM:4216
ChrM:10550
ChrM:11923
ChrM:15257
ChrM:4048
ChrM:14798
ChrM:12007
ChrM:15452
ChrM:5460
ChrM:14766
 

kday

Senior Member
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Here are some mitochondrial positions that are listed as in the 1 to 10 percentage frequency range but we're listed as novel and I tried to look them up.

ChrM:12501
ChrM:13708
ChrM:4216
ChrM:10550
ChrM:11923
ChrM:15257
ChrM:4048
ChrM:14798
ChrM:12007
ChrM:15452
ChrM:5460
ChrM:14766
For some reason, medical likes to ignore the mitochondrial variants. Surprisingly, there isn't a well curated frequency databases. A lot of variants are just part of your haplogroup/subclade. And some variants are risks for disease that exist within that haplogroup or sublclade.

I plan on adding frequencies for mtDNA variants, because it's confusing how variants with frequencies of 10% are marked as pathogenic.
 

nandixon

Senior Member
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@Brandit, Just to add, there are a little over 16,500 positions in the human mitochondrial genome. Of those, each person only has on average about a couple dozen positions where there are nucleotide variations from the reference genome. I have 40, for example, which is a little more than average just because of my particular maternal haplogroup (J1c2).

Of the 40 variants, 10 are for my maternal haplogroup, 10 are a hodgepodge from other maternal haplogroups, and the remaining 20 are relatively common variants at positions that are easily mutable.

I think that unless a person has a family history of relatives with vision or hearing problems or cardiomyopathy or intellectual disability, etc. (i.e., common mitochondrial disease issues) it's unlikely that person will have a significant mutation in the mitochondrial genome, as they're usually much more damaging on average than in the nuclear genome. So this may be at least part of why there's a certain lack of interest in providing frequency data for mitochondrial variants.

[On another thread there was initially some confusion (including by myself) that there might be some important variants showing up in people's WGS results but that was just because we didn't realize that companies like Dante and Veritas were using the outdated Yoruba mitochondrial genome as the reference standard instead of the newer Cambridge one, and that many positions were needing to be converted from Yoruba to Cambridge. (Yoruba is built into the hg19 reference genome that both Dante and Veritas use; 23andMe switched to Cambridge several years ago.)]
 
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thanks wigglethemouse, that particular mutation that we share is it something that's actionable through supplementation or do we simply have to accept the limitation? I can't tell what the biochemical shortfall is from that position.

Thanks nandixon, to get such a clear picture of your mutations did you do a full exome or genome? Im also a j1c2 and was curious how you located a standard mutation profile for that halo group.

I think some of the more basic clinical analysis of people projecting mitochondrial diseases such as Leber optic was simply grouping a bunch of common mutations so it was nearly impossible to tell if they were involved or a cause.
Some of the more in-depth clinical analysis show a number of spontaneous mutations that was not shared by some of the other family members.

I wonder if you genome yourself 25 years later you end up with more mutations than you initially started with
 

nandixon

Senior Member
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Thanks nandixon, to get such a clear picture of your mutations did you do a full exome or genome? Im also a j1c2 and was curious how you located a standard mutation profile for that halo group.
I did whole genome sequencing (WGS) with Veritas (which I don't recommend) and was provided with a VCF file which I opened up with a large capacity document reader. I then manually converted each of the 40 mitochondrial variants that were present from their Yoruba referenced positions to Cambridge and looked up each one individually. (See, e.g., https://www.snpedia.com/index.php/MtDNA_Position_Conversions)

If my notes are correct, J1 is determined by having a C → T change at mitochondrial position 462 (which is 464 in Yoruba). J1c is determined by having a G → A change at position 228. And J1c2 is finally determined by having an A → G change at position 188. (Positions 188 and 228 each happen to be the same for both Yoruba and Cambridge, so no conversion for those positions is necessary.)
 
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I wonder how these mitochondrial mutations are impacted when they're combined with a nuclear gene mutation that also involves mitochondria such as Rs119103264 mfn2 gene -- 23andme I number i5008699
 

nandixon

Senior Member
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I wonder how these mitochondrial mutations are impacted when they're combined with a nuclear gene mutation that also involves mitochondria such as Rs119103264 mfn2 gene -- 23andme I number i5008699
If the variant for that SNP is showing up for you with @kday's program, can you post a screenshot of what you're seeing? There appear to be some inconsistencies in different databases which is making me think that one might possibly be a miscall by 23andMe. Not sure yet though.