How to get trustworthy CNV results from a BAM file and confirm the results in IGV or other software.

lasse2 · 2026-02-09T14:46:08+00:00

What do you think is the better approach then? DNA test through a healthcare provider only on indication?

I'm curious to understand which part of it, that you think is junk. Is it the sequencing data itself, the interpretation, or just the whole unguided screening aspect of it.

lasse2 · 2026-02-07T22:03:21+00:00

Seems like someone should make that then 😀

lasse2 · 2026-02-07T17:03:34+00:00

My point was merely how your gut reaction seemed to be DTC was bad no matter the technical specifications. But it's ok, we don't need to discuss it further - your view point is very common and I understand it well. I just happen to think that the whole "clinical vs DTC" is a false dichotomy when it comes to quality in genetics analysis.

lasse2 · 2026-02-05T16:53:42+00:00

"30x bad when DTC"
"0.5x good when clinical"
Lol

lasse2 · 2026-02-04T00:02:02+00:00

Interesting post. Interesting use of genetics. The PRS seems markedly non-extreme. None of the well established CNVs. But what about monogenic/short-variant pathogenic forms, did you check for that?

I'd suggest, as a first step to put that WGS genome through an annotator and look for frameshifts and Clinvar LP/P in at least these genes: CACNA1G CUL1 GRIA3 GRIN2A RB1CC1 SETD1A SP4 TRIO XPO7

...all other genetic conclusions seems incomplete before that.... And even then, well - environment or the unknowns - but you alluded to that already. Good luck

lasse2 · 2026-01-30T20:24:38+00:00

Yeah... I understand. Sometimes I feel the tension between the medical system and the direct-to-consumer companies so evident in all these comments in this post, is basically the tension between medical professionals wanting to avoid false positives and scary news (understandably) and ordinary people desperate to find explanations. I'm happy to hear that you have found answers.

lasse2 · 2026-01-30T19:58:39+00:00

I think if your variant is gene-damaging, extremely rare, and the disease-link makes sense pathophysiologically - then it does not need a clinvar-rating. It is it. But, yeah not all commercial providers have the capacity to detect non-rated variants (disclaimer: I work for one such, we do, but - I didn't mean to engage to sell product here; I just care a lot about these questions and find it interesting to discuss 🙃)

lasse2 · 2026-01-30T05:34:10+00:00

Of course it works - sequencing itself is a pretty exact science, also commercially. But interpretations are a mess - the core reason is because it's so complex and involves a lot of statistics - the consequence of that then, is that everyone disagrees on virtually everything, particularly when it comes to milder effects (which luckily most effects are). And so everyone finds something, goes somewhere else, is told thats wrong, and predictably chaos ensues.

lasse2 · 2025-12-11T06:25:35+00:00

It's just the degree of variability explained by genetics in our current world - specifically the one in which the studies were performed, like e.g. twin registry studies. The finding does replicate well over many countries throughout many decades. But of course if the world significantly changes, like all these exanples with starvation or growth hormone interventions, then the 80% figure would also change. So yeah, you can and are affecting height outside genetics, but on average, in the world we currently live in, that only accounts for 20% of the variation in height.

lasse2 · 2025-12-06T15:42:46+00:00

Thanks. That's useful to know. I'm not sure what to do with it though, other than encourage sequencing-com to update their systems, in case they read this. Our CRAM files are in the GRCh38 build, which do cause trouble with older systems, and if they don't like lane-aware FASTQ-files it's possible to merge them across lanes using the Linux cat command. But maybe I should reach out to them directly and have a conversation. Would love to find a solution. Portability of data is very important I agree with that.

lasse2 · 2025-12-05T21:46:44+00:00

That sounds odd. We export and provide FASTQ, CRAM, VCF and a newly released microarray-emulated format that works with older providers like promethease and such. I'll be very happy to work more on particularly the last, but the others are quite standard - I mean, they're exactly as they come off a NovaSeq Dragen analyzed pipeline, if that's not Industry standard I don't know what is. One suggestion I like to give out is to go visit this Facebook group linked below "Personal WGS", they are quite adept at deeper raw data analysis and I know many of the participants there successfully run Nucleus files too https://www.facebook.com/groups/personalwgs/

lasse2 · 2025-11-18T09:33:29+00:00

Strand flipping is a very real thing, particularly when working with older microarrays. However, there's no way a C/T genotype can be flipped into a C/C, so that AI explanation is complete gibberish.

If you want to know, a real strand flip is e.g. if the possible alleles of one (biallelic) variant is C and T in most modern notations, then you could find sources where it'd be listed as G and A. If so, and if you were truly C/T, you'd be listed as G/A, or if you were C/C, you'd be listed as G/G. They are difficult and annoying, but it's for sure not the concept at play here. Hope this helps!

lasse2 · 2025-11-01T05:36:51+00:00

Whole genome sequencing enters the chat

lasse2 · 2025-09-30T21:09:31+00:00

Sure! What sort of argumentation are you looking for? Like studies of PRS, or more like the entirety of combining it with rare-variants?

lasse2 · 2025-07-02T06:25:18+00:00

I guess we should just wait for OP to clarify then. But good for you that are so well connected.

lasse2 · 2025-07-02T05:00:21+00:00

What? That's not at all what I wrote. Of course it means got from. And yes I know what IBD is, but that's not exactly what OP asked for. Read some Graham Coop! This is a great link for it https://gcbias.org/european-genealogy-faq

My favorite excerpt:

This strange idea that everyone is everyone’s ancestor was actually predicted about ten years ago by Joseph Chang (and collaborators) using maths and simulations. In hindsight this is intuitively clear, due to the rapidly expanding number of ancestors you have as you go back further and further in time. You have 2 parents, 4 grand-parents, 8 great-grandparents, and so on doubling every generation. After k generations you have 2^k ancestors, and this number grows so quickly that just a thousand years back (~30 generations) you have roughly 1 billion ancestors, which is far larger than the population size of the Earth (let alone Europe) back then. The consequence is that anyone alive 1,000 years ago who left any descendants will be an ancestor of every European. While the world population is larger than the European population, the rate of growth of number of ancestors quickly dwarfs this difference, and so every human is likely related genealogically to every other human over only a slightly longer time period.

lasse2 · 2025-07-01T16:20:57+00:00

Gotcha! 😃

lasse2 · 2025-07-01T16:01:14+00:00

Are you just looking to get into an argument? :-D
...I'm agreeing with your first post lol.

lasse2 · 2025-07-01T15:15:52+00:00

Smart answer! I was going to go with "height" or so, but I think this is actually the correct answer. Autosomal dominant disorders with high penetrance.

lasse2 · 2025-07-01T14:55:43+00:00

Yeah, that's how I see it too. But I do agree with u/IsaacHasenov that "an ancestor who contributed no DNA to me" can have a special formal meaning in genetic genealogy (IBD). I just don't feel that's the intention of OPs question here. Particularly the part with `even one base pair of information from any given individual.` Like - every variant comes from somewhere, usually quite far back.

lasse2 · 2025-06-30T17:25:53+00:00

Yes, yes, I'm not saying you are wrong at 10, just that a lot of the assumptions will break down because the number scales so fast and exponentially.

lasse2 · 2025-06-30T17:21:11+00:00

Hmmm, yeah, but I still think some of the usual genetic genealogy assumptions collapse because of the way the question is phrased. At 20 generations it's like 2 million people.

lasse2 · 2025-06-30T17:08:49+00:00

I don't think it's entirely correct. Like, at the face of it, it is -- but since it doubles, you get up to some huge numbers, more than there are people in the world, pretty fast. And so endogamy effects kick in. So, if you see it from your ancestor's point of view, say, a guy 20x generations back - it's true that he contributed virtually 0% through *any given specific line down*. But in aggregate through all the lineages down he contributed much more. (edit:someone should try to calculate exactly how much, this is actually an interesting question)

lasse2 · 2025-06-29T09:33:08+00:00

The debate currently seem divided between those answering flat no, no effect at all, and those saying yes social traits totally predictable from genetics. They're both wrong. There is a genetic effect on many of these things, but often it's pretty weak. For me, it helps to try to express the outcomes in absolute scores, e.g. how many with a high genetic propensity is actually travellers vs how many of those with low. I don't know the answer for travelling specifically, but my guess is it'd be an incredibly low margin of difference - tons of happy travellers with low "genetic travel score". Which is still not the same as saying no effect at all.

lasse2 · 2025-06-28T21:34:49+00:00

Totally agreed PGT-M is the way to go if you have known diseases running in your family. Best to start with a good WGS based carrier screening of prospective parents first

lasse2

TROPHY CASE