Ryan is a Ph.D. candidate studying translational human genomics in the Bioinformatics and Integrative Genomics program at Harvard Medical School. He is supported by an award from the Graduate Research Fellowship Program (GRFP) through the National Science Foundation (NSF).
- @Dariloops @Phil_A_Richmond @NatureGenet Admittedly, #1 was the focus of the NG study, not #2, so on that basis I agree different contexts is an important confounder But like your 2015 paper clearly shows, some disruptions have severe consequences that matter more than expression of the run-of-the-mill arbitrary gene
- @Dariloops @Phil_A_Richmond @NatureGenet This is a really useful perspective. To me, this becomes a two part question: 1. What % of TAD disruptions lead to expression differences in any context; vs 2. What fraction of those same disruptions have phenotypic consequences My guess: #1 >> #2, but #2 likely a subset of #1
- @Phil_A_Richmond @NatureGenet @Dariloops Sorry, I was using developmental genes as an example for the most sensitive/critical genes — I am sure there are other groups of genes with important TAD-mediated regulation, but the vast majority of genes probably are not in this category
- Just like genes, by analogy: a select few of them are truly critical for normal development, while ~most can tolerate disruptions without incurring large fitness deficits on the cellular or organismal level