tag:blogger.com,1999:blog-1812431336777691886.post7435421508644856842..comments2024-02-29T03:57:00.088-05:00Comments on The Mermaid's Tale: The tail that doesn't wag: Why?Anne Buchananhttp://www.blogger.com/profile/09212151396672651221noreply@blogger.comBlogger2125tag:blogger.com,1999:blog-1812431336777691886.post-83865478232261127092015-04-30T15:03:45.837-04:002015-04-30T15:03:45.837-04:00Peter,
As far as you go, one would agree that this...Peter,<br />As far as you go, one would agree that this is the general gist of population genetics views of things. But the jury is still out as to the degree to which missing heritability is due to interactions, and the traits being studied are largely post-reproductive and not affecting fitness. Even just additive contributions should be less diverse in the tails of the distribution by the usual, if informal, model assumptions. If very large, individual-specific collections of very rare, mainly very weak, factors are responsible our typical models will not be finding them (and they aren't). Also, things are similar for non-disease traits. I do think that selection by nature and prediction by Francis Collins are similar in terms of allelic or genotypic effects.<br /><br />Interactions need not be simple pairwise ones, however. An allele can interact in a distribution of ways depending on context. Some may put the result in the tail of the trait distribution. Our models just aren't looking for things like that, in my view, and I don't think anything I've said here disagrees with your comments.Ken Weisshttps://www.blogger.com/profile/02049713123559138421noreply@blogger.comtag:blogger.com,1999:blog-1812431336777691886.post-92031786075277582532015-04-30T13:42:17.942-04:002015-04-30T13:42:17.942-04:00Epistasis and dominance effects will prove to be t...Epistasis and dominance effects will prove to be the key in my opinion.<br /><br />The vast majority of studies can only detect the additive effects of a given allele on a trait. If an allele promotes phenotype P on one genetic background, but not on another, then the study will be blind to it.<br /><br />We could have predicted this right back at the start for any phenotype that has significant effects on reproductive success. Natural selection will eliminate any alleles that have significant additive detrimental effects on fitness. It will by definition leave only those alleles where the causal chain is too obscure/indirect to allow selection to operate. These will thus also be too obscure/indirect to be detected in our studies, and too contingent on other factors to be useful for prediction.<br /><br />Short version: If you can use a given gene variant to reliably diagnose or predict a disease, then evolution can, will, and already has gotten rid of it.Peterhttps://www.blogger.com/profile/12559721137290332762noreply@blogger.com