3 ms·
You're assuming that associations to blocks of linked genotype is the end of the story. Yes, an association to a phenotype using data like that sourced from 23
by searine 4y ago
You're assuming that associations to blocks of linked genotype is the end of the story.
Yes, an association to a phenotype using data like that sourced from 23&me only generally points in the direction of the genes and snvs which cause alterations in phenotype, but that is just a stepping stone.
It narrows down the search space to about 1-2% of the genome, which then follow up studies can fine map. Using high resolution data, such as whole-genome or exome sequence, you can then pinpoint protein-coding changes which alter phenotype. This is what a lot of people are doing right now, using the last decade of GWAS results to fine map using WGS.
If you discover exactly how the machine breaks, it is a lot easier to fix it, or at least prevent it from getting broken in the first place.
It is not a simple as flipping one switch, and it is an incremental 'boring' process, but the potential to better understand disease today and in the future is worth its weight in gold.
- dekhn 4y agoThese are organismal phenotypes which have no direct correlate to molecular phenotypes (because they are complex and caused by entirely nontrivial developmental processes). Even if you knew the proteins involved you couldn't craft a realistic model that explained the observed organismal trait from the protein variations using any amount of existing scientific methods. Obviously this isn't true for some diseases, such as simple mendelian diseases caused by single SNP changes. I worked in the field for decades and very little progress has been made mapping genotype to complex organismal phenotypes or appreciating how complex development processes are affected by collections of mutations. This specific research, even if wildly successful, wouldn't really have impact on any significant diseases.