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> you could have a trillion unique variations of the genome It's not really as bad as it sounds. The vast majority of those small mutations must be in the non-

> you could have a trillion unique variations of the genome It's not really as bad as it sounds. The vast majority of those small mutations must be in the non-coding and non-regulating zone, with no effects on the genome's functionality. As the article mentions[1], it's an interesting line of study, but let's not jump to conclusions. [1]: "[...] each neuron may harbor hundreds of somatic mutations. Given the long life span of neurons and their central role in neural circuits and behavior, somatic mosaicism represents a potential mechanism that may contribute to neuronal diversity and the etiology of numerous neuropsychiatric disorders." - http://science.sciencemag.org/content/356/6336/eaal1641 http://science.sciencemag.org/content/356/6336/eaal1641

jboggan 9y ago
One major trend over the past 20 years has also been the realization that "non-coding" regions tend to be anything but, their effects are subtle and still being discovered.
- patall 9y ago
  Nevertheless, it is long being observed that for example in cancer most mutations are passenger mutations. And this is true even more if they come from non-coding regions. Honestly, I am a bit surprised that you claim to have a bioinformatics background and are surprised about somatic variants. I mean, they are observed everywhere in NGS (and used on a daily basis for tracking pluripotent stem cell clonality and other things), there is not much surprising about it anymore.
  - jboggan 9y ago
    My unfinished PhD dissertation was about the topological differences in metabolic pathways expressed by various cancer cell lines in contrast to healthy tissue as a means of targeting metabolic "choke points" for future drugs - I'm not surprised about the existence of somatic variants but I am looking back and realizing how many of us were taking the uniformity of our systems for granted. Even when modeling the differences in a rapidly mutating cancer we always treated the variants as collections of discrete mutations that were uniform across the cluster. Then again this was ten years ago and you couldn't even think of sequencing enough lines to get at a cellular resolution. This really makes me want to pick that back up.
- deleted 9y ago
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- dekhn 9y ago
  This is an argued area, but I think most people would agree that LTRs, which make up the bulk of non coding regions, have effectively zero effect on functional selection. There are many regions which are non-coding which appear to be under selection and play functional roles, but (and this belief only changed after looking into the problem in some detail) most of the LTR regions have no effect.

jboggan 9y ago

One major trend over the past 20 years has also been the realization that "non-coding" regions tend to be anything but, their effects are subtle and still being discovered.

patall 9y ago
Nevertheless, it is long being observed that for example in cancer most mutations are passenger mutations. And this is true even more if they come from non-coding regions. Honestly, I am a bit surprised that you claim to have a bioinformatics background and are surprised about somatic variants. I mean, they are observed everywhere in NGS (and used on a daily basis for tracking pluripotent stem cell clonality and other things), there is not much surprising about it anymore.
- jboggan 9y ago
  My unfinished PhD dissertation was about the topological differences in metabolic pathways expressed by various cancer cell lines in contrast to healthy tissue as a means of targeting metabolic "choke points" for future drugs - I'm not surprised about the existence of somatic variants but I am looking back and realizing how many of us were taking the uniformity of our systems for granted. Even when modeling the differences in a rapidly mutating cancer we always treated the variants as collections of discrete mutations that were uniform across the cluster. Then again this was ten years ago and you couldn't even think of sequencing enough lines to get at a cellular resolution. This really makes me want to pick that back up.
deleted 9y ago
[deleted]
dekhn 9y ago
This is an argued area, but I think most people would agree that LTRs, which make up the bulk of non coding regions, have effectively zero effect on functional selection. There are many regions which are non-coding which appear to be under selection and play functional roles, but (and this belief only changed after looking into the problem in some detail) most of the LTR regions have no effect.