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Comment by hartator | Hacker News Reader

Very few companies even scan your entire DNA. 23andMe analyzes for example maybe less than 1 or 2%.

It's way less than that. They scan SNP's, of which there are about 10 million in total. So only 0.3% of the human genome varies between all of us. I think they only do the 602,000[1] most common SNPS, which is only 0.02% of the genome though they might do a few more.

A SNP is a Single Nucleotide Polymorphism, ie places in the genome which vary from the reference human genome by change of one base pair. [1] https://www.snpedia.com/index.php/23andMe_v4_differences

Presumably most (98% isn't it) of our DNA is the same thought, right?

About 98% of our DNA does just makes an ordinary human body with normal systems.

So we're only interested in the 2% that can vary.

Or whatever the actual numbers are.

I think 23andme's genotyping is about 1% coverage compared to whole-exome sequencing, which itself sequences the ~1% of your DNA that codes for proteins.

It's not that only 2% _can_ vary, it's that each person has about 2% different from the reference genome (and that 2% is different for every single person).

And only a small subset of that 2% is able to cause pathology pathology.

So any diagnosic or risk predictive tests need only check those areas know to result in or increase the risk of pathology.

That's not at all true. For rare, undiagnosed disease we have to sequence the entire genome in order to look for the causative variants. For well understood (common) genetic disease we have small panels, but to say that only a small portion of the genome is informative is not correct. Additionally, there is no way to know a priori which loci will have the variation without sequencing the entire genome.

A single error in the very large part of DNA that shouldn't vary per individual but "makes an ordinary human body with normal systems" means that you don't get an ordinary human body with normal systems.

Many such errors cause non-viable embryos, but if you have survived up to this point, then such a difference is still quite likely to have a meaningful impact to your health and is precisely the part that you'd want to have scanned and verified.

For adult DNA scanning we're not really interested in all the genes vary between all people and code for the color of your eyes, the melanine content of your skin, the shape of your nose or your height - but we are very much interested in, for example, scanning your genes that encode CFTR protein to check if you (or your kids!) will have issues with cystic fibrosis.

It's possible that you don't really have (or your kids are likely to not have) an "ordinary human body with normal systems" - that's what you'd need to find out.

That's right. I'm suggesting the average diagnostic test need only concern itself with those areas of the genome that are know to contain mutations that result in pathologies.

I think you said the same thing but in a clearer way.

I think the problem is that aside from a handful, they are not known. It's like saying you're only going to copy the parts of a program where bit errors are known to cause problems.

>A single error in the very large part of DNA that shouldn't vary per individual

However true, that is irrelevant to genetic diagnostics as they exist today. We have no idea how a random error might impact health aside from very limited known mutations that are sufficiently frequent in the population to enable statistical correlation. We are probably decades away from being able to say, for a random mutation, 'this will lead to a deficiency in the synthesis of protein A which impact the development or working of organ B'. We can't even agree on the proportion of junk DNA.

This is helpful if you have rare symptoms with no currently available explanation - if you get a list of the "unusual" mutations that you have, and correlate it with the same data from the few people worldwide that have the same issue, you get a possibility to improve that condition.

I recall seeing cases of rare genetic disorders that have been diagnosed that way, by online communities sharing data.

http://matt.might.net/articles/my-sons-killer/ is one story that counters "this will lead to a deficiency in the synthesis of protein A which impact the development or working of organ B". For many parts of DNA we do know what protein it makes. For many proteins/enzymes/etc we have some idea about their function in the body - and if we have a test subject missing that protein, then the symptoms will be even more indicative about this, even if the population is tiny (1 in this example!) and doesn't allow for any statistical inference.

This means that if we really want to, we can try to find out the likely effect and possible workaround of a particular mutation, even if we currently don't have a ready-made answer for it.

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