4 ms·
Current estimates are that there’s a roughly 1 in 1000 difference between two individuals purely due to random mutations in the germline (or, put differently, t
by klmr 8y ago
Current estimates are that there’s a roughly 1 in 1000 difference between two individuals purely due to random mutations in the germline (or, put differently, the DNA replication error rate in human cells is about 1 in 1000). This would imply 99.9% expected similarity between two identical twins. However, this is in the germline. Somatic cells accumulate mutations over their life time (since they, too, divide and therefore need to replicate their DNA, and are furthermore exposed to environmental stress). In addition, the tests work off saliva samples which are mixed with all kinds of stuff in the mouth, and degrade slightly during transport. Lastly, there’s an inherent replication variability in the genotyping process (though this is very small).
This back of the envelope estimate suggests that 99.6% similarity for somatic samples of identical twins is not unexpected.
- opportune 8y agoSomething tells me that the 1/1000 error rate you cite isn't truly accurate, or at least doesn't apply to all portions of DNA equally, because in almost every individual that would result in many SNPs with bad consequences since we have so many subsequences coding essential proteins
- adenadel 8y agoThis is not accurate. Coarsely, there are roughly 3 million SNPs (out of 3 billion total haploid bases) per individual. When we talk about individuals "sharing" DNA we mean these variants and not the 99.X% of DNA that we all have in common. When we refer to random mutations in the germline (i.e. de novo variants) current estimates of de novo variants per individual are in the low hundreds. The other factors you discuss are more likely to cause issues. One major one is the error rate of the microarray because of the high number of genotypes being assayed. If the chip has an error rate of 0.1% and 500k tests are performed you would expect 500 mis-calls. I used to work for Illumina, who makes these chips, but I worked on the DNA sequencing side of things so I don't know the actual error rate off the top of my head.
- klmr 8y agoRight, de novo mutation rate is much lower (even lower than what you wrote, just slightly above 1e-8 according to deCODE). The 1/1000 rate is the average difference between two random individuals (not twins), which corresponds to your 3M SNPs per 3B bases.
- adenadel 8y agoYes, but you referred to them as random mutations, which is not the case. They are inherited variants. The DNA replication error rate is nowhere near 1 in 1000.
- klmr 8y agoHence my correction. Without looking it up now, the actual replication error rate is probably close to the deCODE rate for de novo mutations (modulo gamete selection, so probably higher than that).