<p>In theory, almost any base in the human genome may mutate, so you have billions of variants to go. Ok, this is not so useful.</p>

<p>A related and potentially useful question is: given a human, what is the fraction of his/her variants seen in the the previously sequenced samples? For a Wright-Fisher population, there is an analytical answer: x% of variants on a haplotype has frequency below x%. Replace "x" with "1": 1% of variants on a haplotype have frequency below 1%. The 1000 genomes project concluded that 99% of SNPs at frequency 1% or higher have been called by the project. If we all came from a Wright-Fisher population, 99% of of SNPs have been called in 1000g. Given that the project also calls SNPs at lower frequency, nearly all SNPs in a newly sequenced sample are present in 1000g.</p>

<p>The above is a theoretical analysis. In practice, there are two major complications. First, we are not a Wright-Fisher population. Due to recent population expansion, each haplotype harbors more new mutations than the Wright-Fisher model would predict. Given a known population history, it is actually possible to numerically compute $f(x)$, the fraction of variants with frequency below x (for Wright-Fisher, $f(x)=x$). I don't have this result, though. Second, 1000g and many other genome projects didn't call SNPs in repetitive regions and missed a significant portion of high-frequency indels and structural variations. With Illumina, you can only call ~30% of long deletions callable with PacBio data, but we only have a dozen of PacBio human genomes in public. There are still a lot we don't know.</p>

CC BY-SA 3.0
2018-01-22T00:16:47.497Z
2018-01-22T00:16:47.497Z
user172818
<p>Given all the genome variation information we have accumulated from resequencing human genomes up until now (early 2018), how much variation is left that hasn't been sequenced?</p>

<p>EDIT: given one of the answers, and the fact that 99% of the SNPs at 1% or more are found, is there a quantitative measure of remaining variation?</p>

CC BY-SA 3.0
2018-01-21T23:37:43.470Z
I don't think this is answerable. Do you mean single nucleotide variants? Copy number changes? In healthy individuals only? Only living individuals? All possible variants? Pretty much *anything* is possible. . .
terdon
CC BY-SA 3.0
2018-01-22T09:02:08.653Z
Please clarify "variation". If you limit this to single nucleotide polymorphisms only and to variants above a certain frequency threshold, as the answer you have received has done, then it might indeed be answerable.
terdon
<genome><snp><human><variation>
remaining human genome variation that hasn't been sequenced?
# remaining human genome variation that hasn't been sequenced?

(Asked by: username_0 on 2018-01-21)

Given all the genome variation information we have accumulated from resequencing human genomes up until now (early 2018), how much variation is left that hasn't been sequenced?

EDIT: given one of the answers, and the fact that 99% of the SNPs at 1% or more are found, is there a quantitative measure of remaining variation?

**Tags:** genome, snp, human, variation
> **Comments:**
> **username_1**: I don't think this is answerable. Do you mean single nucleotide variants? Copy number changes? In healthy individuals only? Only living individuals? All possible variants? Pretty much *anything* is possible. . .  
> **username_1**: Please clarify "variation". If you limit this to single nucleotide polymorphisms only and to variants above a certain frequency threshold, as the answer you have received has done, then it might indeed be answerable.  

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## 1 answers

### Answer by username_2 on 2018-01-22. Score: 5

In theory, almost any base in the human genome may mutate, so you have billions of variants to go. Ok, this is not so useful.

A related and potentially useful question is: given a human, what is the fraction of his/her variants seen in the the previously sequenced samples? For a Wright-Fisher population, there is an analytical answer: x% of variants on a haplotype has frequency below x%. Replace "x" with "1": 1% of variants on a haplotype have frequency below 1%. The 1000 genomes project concluded that 99% of SNPs at frequency 1% or higher have been called by the project. If we all came from a Wright-Fisher population, 99% of of SNPs have been called in 1000g. Given that the project also calls SNPs at lower frequency, nearly all SNPs in a newly sequenced sample are present in 1000g.

The above is a theoretical analysis. In practice, there are two major complications. First, we are not a Wright-Fisher population. Due to recent population expansion, each haplotype harbors more new mutations than the Wright-Fisher model would predict. Given a known population history, it is actually possible to numerically compute $f(x)$, the fraction of variants with frequency below x (for Wright-Fisher, $f(x)=x$). I don't have this result, though. Second, 1000g and many other genome projects didn't call SNPs in repetitive regions and missed a significant portion of high-frequency indels and structural variations. With Illumina, you can only call ~30% of long deletions callable with PacBio data, but we only have a dozen of PacBio human genomes in public. There are still a lot we don't know.


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