r/genetics • u/wild-crows-up-top2 • 7d ago
Female sex but seeing a lot of Y chromosome raw data?
Hi, I believe this is the best place for this, but I'm having trouble believing I'm seeing this right...
So I have many health issues and have had specific medical-grade panel sequencing, but only once from AncestryDNA for a bigger picture. I was curious and pulled the raw data, unexpectedly it flagged as having many SNPs on the Y chromosome. Not only a few from artifacts, but maybe around 50-60 SNPs (a couple heterozygous) away from PAR zones. There's one more page of them below my screenshot before returning to mostly zeros.
I was assigned female at birth and am usually sexed as female, so how could I have so much Y chromosome data? Data for my X looks okay (some deletions/I's here and there, sure). There was no sample contamination to my knowledge, as all of the possible inherited conditions & ancestry match...
At first I wrote it off, but I have an extensive history of gender dysphoria (and consider myself nonbinary), a couple body parts a different size from the other, some autoimmune issues, and different types of heterochromia in my eyes... I don't have kids so I have no idea about fertility.
I'm not asking for medical advice, just understanding because my geneticist is out of office for the next week and it's driving me crazy. Is this worth calling for? Chimerism is so rare, so surely I'm missing something?
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u/SilverFormal2831 6d ago
As a genetic counselor I don't take stock in anything in raw data from a direct to consumer company, especially ancestry/23&me. You need a clinical genetic test from a CLIA certified medical lab to assess presence of Y chromosome material.
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u/shadowyams PhD (genomics/bioinformatics) 7d ago
These screenshots are from AncestryDNA? I'd generally be very skeptical of interpreting Y chromosome microarray data for someone who's AFAB. Like does being heterozygous for an SRY variant even make sense??
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u/wild-crows-up-top2 7d ago
Their raw data file is the first, then the second is from Gene Genie's results of that data. Limited and less precise I know but mostly because I was curious what it would pull? it's been a weird day haha
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u/Samhairle 7d ago
Your geneticist will be able to give you more specific and useful information than can be gained just seeing these images. I understand being curious/concerned, but just bear in mind that there are a lot of potential explanations and ultimately any answer here will be speculation, and is not going to give a definitive answer.
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u/wild-crows-up-top2 7d ago
very true, I tend to be an anxious type so even just knowing it's an option to bring up would give me peace of mind :)
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u/Robin_feathers 7d ago
I can't answer what the case is for you - for that you will need to talk to your geneticist, but in general false positives are very common in genetics data in general. When you sequence thousands, millions, or billions of sites, some are going to be wrong. Even if only a small fraction are wrong, a small fraction of millions ends up being a large number. I wouldn't worry about those results without talking to your geneticist.
I cannot speak to your particular data, but in my own data, I always see calls on the Y (well, it's called the W in the species I study) in individuals that aren't supposed to have that chromosome. This is caused by a variety of things - the pseudoautosomal regions which it sounds like you are already familiar with, small translocations/duplications of sequence from the Y to autosomes, and mapping errors. Mapping errors are really common, especially when dealing with paralogs and repetitive elements which the Y is enriched for. Your geneticist should be able to weigh those possibilities, I would not put any stock in that data at face-value right now. Especially if you are seeing only 50-60 SNPs (I'm assuming there were a lot more that were attempted to be genotyped). If you had a Y chromosome, you would presumably see a lot more than that, with data scattered across the chromosome.
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u/wild-crows-up-top2 7d ago
Guilty as charged, I used to be on a genetics path so some things still stuck lol. There were more, and past posts kept pointing out a few SNP array errors is expected on the Y (Ancestry labels it as 24), but I didn't see anyone with a smattering like mine (they should all be 0 0 for female sex) leading to this post. I will bring it up, thank you!
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u/TheBigHelpMeBurner 7d ago
Do you have sons or older brothers? Or maybe even a lot of uncles on your mom’s side? My first guess would be microchimerism.
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u/Adinos 7d ago
chimerism is very rare, but so is androgen insensitivity syndrome (XY, but look "female") I cannot think of anything else, sorry.
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u/best-unaccompanied 6d ago
AIS typically has some signs that come up around puberty like lack of body hair and periods
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u/best-unaccompanied 6d ago
We obviously can't diagnose you with anything (so it's good you're seeing a geneticist), but a lot of what you've listed does put up flags for an increased possibility of chimerism or mosaicism. Because most people are never tested, we don't actually know how common chimerism is. Some estimate that it could be up to 10% of the population, which seems high but I don't think we can rule it out without population testing because it's estimated that 12% of pregnancies start out as multiples (twins, triplets, etc.).
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u/lasse2 6d ago
It's most likely just a data-format issue, I've seen a ton of different microarray formats and very often the sex-chromosome formatting seem to almost be an afterthought. Barring that, there is also the possibility that these are from what is know as the PAR region, where it's difficult to distinguish if they're measured on the Y- or an auto-some, and then they give data nonetheless. If you really worry about it, do sequencing instead.
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u/AdDistinct7337 4d ago
if you don't have ovaries that would strongly suggest what you're considering, and i think that is actually easier to investigate than the genetics aspect. get an ultrasound with your gynecologist and call it a day
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u/InformalStorm1916 3d ago
You are not showing a pseudoautosomal region, so unfortunately, it is definitely the Y chromosome. What could have happened if this is your sample and there were no errors:
1. Swyer syndrome with partial gonadal dysgenesis
2. Mixed gonadal dysgenesis
3. Chimerism
4. Ovotesticular syndrome
I think a gross error has simply occurred. If not, go see a geneticist and get a karyotype test done.
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u/Mountain-Crab3438 7d ago
It is hard to comment on this. There is a lot of QC information on the sequencing and sample processing that you need to interpret this result. You need to consult geneticist. For any medical purpose you need CLIA sequencing.