There were four talks at the workshop that I went to yesterday. All of them were good - I was in what was essentially a classroom listening to talks for close to four hours and didn't once get drowsy, a very good sign. I wrote about one of them yesterday, one was from Jennifer Becq from Illumina, largely about exactly how fast they can go from taking a sample to finding variants in a persons genome - thinking finding the mutations that might be responsible for someones cancer. It's very fast, as in less than a week. Very cool stuff they're doing there. And one was from Fiona Nielsen of DNAdigest, the people who were running the workshop. They've got some nice ideas about how to make it easier to share data, increasing the power of all the data that is currently locked up in various public institutions.
The stand out talk of the workshop for me though, was from Mette Nyegaard of Aarhus University. There is an extended family with a genetic predisposition towards deafness. Some of the family are born deaf. Some become deaf when they are six. Some become deaf in their twenties. She started off with linkage analysis to identify where in the genome the problem is - she started with 50 known genes and 80 loci (where the general area is known but not the actual gene is located) involved with hearing loss. Her analysis narrowed this down to 1 loci. Which was a nice start.
There were multiple false starts with candidate genes being misidentified - sequencing and analysis eventually knocking out various contenders. There were some interesting bits in here that I don't fully understand, I need to read up on her work, but there were candidate genes that looked iffy, which once sequenced were shown to be completely normal - there was a pseudo gene duplicated from the same gene, in the same region that was making it look damaged. And another one that appeared to be responsible but then turned out to be present in the greater population with no ill effect.
She finally tracked it down to a 18 base pair deletion which had initially been interpreted as a frame shift mutation. That 18bp deletion though appears to be a sorting signal responsible for moving the protein from the cell surface to the lysosome (where it would normally be degraded). Even with all the work she's done, it's not guaranteed that this signal is the cause of the deafness. This is the only likely candidate in the coding region of the loci. If this doesn't pan out - then it will be off to look at the regulatory regions of the loci, to see if there's anything abnormal there.
The next step is apparently an animal model (the signal part of the protein is highly conserved across many species) . Which could be tricky - another reason to be impressed is that none of this research has been externally funded in any way shape or form. It's taken a long time because of that. Animal models however require money. Imagine though if she did get an animal model, you could get a time course of expression in the cells in the ear where the problem occurs. And then possibly go further than identifying the mutation that causes the problem, but the process behind it.
Sigh. I don't really feel like I've done justice to her talk here, it was yesterday and I need coffee. I'm going to have to do some reading. It was a thoroughly good talk though. I'd like to try and make this clearer, but it'll have to wait. The conference proper starts today. And I have a sneaking suspicion that as of tomorrow I'm going to be inundated with things I'd like to write about.