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Friday, October 14, 2011
Non "allelic" variation - thinking out loud
(Later Note: I wrote this before I knew what it's called. The term most people use is "Somatic Mosaicism". Apparently this is a pretty well researched topic... so I can go back to all the biologists that looked at me like I was crazy and tell them .... hmm.) Here's a link to a good article on the topic: Original rant below... But let's assume 30 is our number. It's nice and small. And it's good to have a lower-bound. That is only the set of variants that went into the "first cell" (fertilized egg) of an organism. When that egg divides, half the organism has another, different, set of mutations. So 100% of the organism has 30 de-novo mutations and 50% of the organism will have *another* 30 de-novo mutations (30 new ones in that 50%, plus 30 original). But wait, there's more. When those 2 cells divide in half again, you now get 60 new mutations, 30 from each cell. These 60 will be detectible at the "25%" level ... IE: 25% of the final organism will have them. High-throughput sequencing can readily detect variation at the "1%" admixture level. That is, commonly detect variation when as little as 1% of the cells have that variation. So how much variation can we expect, based on a low de-novo mutation rate, detectible at the 1% level? 100%->30, 50% ->30, 25% ->60, 12.5% ->120, 7.25% ->240, 3.12% ->480, 1.6% -> 960 So we can expect about 1000 de-novo variants in a healthy individual, or 32 times the mutation rate. But what if the somatic mutation rate is higher, say, 3000 variants per replication? This may be the case in some organ development. Thus, at the 1% level, would that be 96000 non-inherited detectable variants. I would call that my "upper bound". In real pileup data... I see around 30% "non-allelic" variation. So if, say, you've got 15000 SNPS (a reasonable number), we would expect 5000 "background" snps.....putting the mutation rate at "156.25" (5000/32). That's smack in the middle of the e-coli based estimate. Lots of variant callers filter these out.... but I'm interested in them... i think they may be a lot more important than people think. [View/Post Comments] [Digg] [Del.icio.us] [Stumble] |
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