NF52, do you know of any online AD mouse databases? It would be best to not reinvent the wheel if this can be avoided. It was only recently that I heard of research into what might be our specific family AD gene. I suppose that the lab then starts by designing some CRISPRed mice.
I actually was quite surprised how easy it was to find this suspected variant.
I took an exome file; loaded it up to the CADD site and then it reported back a few thousand variants of interest.
There might have been about 200 fairly high CADD readings, and possibly about 50 very high readings.
The big problem with the CADD software is they did not include MAF, so this made it somewhat tricky.
Though I was able to find this data.
What was interesting was that there was a frameshift mutation with a CADD over 30.
This seems to be the one. Super rare and published research linking it to AD.
I can now go online and find a whole bunch of reality with this same segment.
I am moving to full genome sequencing, so I think it would be a good time to start
pushing some relatives to also confirm that they have this variant.
It would probably be an easier sell if I could direct them to a $50 high read exome sequence, though I am unsure whether
these are on the market. The current alternative wold be ~$300 whole genome sequence which for some would be pricey.
It might be worthwhile thinking about how our forum could help enable others to go through this research. Perhaps we could give the instruction for those to follow, ask them to provide epsilon 4 gentoype, polygenic score and then post their CADD results on a thread on APOE4; if possible we could allow people to do this anonymously without recording their IP address. I find it exciting that
we might be able to help unravel the genetics of AD through such an effort. This could be even more powerful if multiplex AD families uploaded their results. The variants of interest might quickly become obvious.
The million AD snowflakes was more of a personal dread. APOE e4s have been so fortunate to have an entire political lobbying arm based upon the tens of millions of epsilon 4 carriers. There are a select few illnesses that have a bypass budget (cancer, AIDS and AD). It is a rare thing in politics to have bipartisan agreement on anything; yet there is for AD.
My concern though is that at some point this magic might run out. For all of the thousands of others of medical problems it did.
Specifically, what happens as we move away from the core shared feature of amyloid and tau? The newest GWAS that you cited, included synaptic function etc.. The problem that might arise is that there might be a whole bunch of such additional brain vulnerability pathways that branch out into endless complexity.
Thank you for the SNP!
Yes, I could be absolutely swamped when they drop that 100 gigabit file on me.
It is hard to imagine not being swamped with 100 gig.
I expect that the majority of those who receive their full genome scan after about a week curl up
into the fetal position and go on a chocolate binge. How could it possibly make any sense?
That is where the polygenic software etc. will be helpful.
Most of the variants probably will have minimal relevance.
However, when yo add them up into a PGS then an IQ estimate might emerge etc..
This is a step into the future.
It is one of those look in the mirror moments that one would rather avoid.
How smart am I?
How mentally stable?
Society will be genetically organized by these results.
Unselected school rooms might not be sustainable even over the next 5 years as full genome sequencing goes
mainstream. The future is approaching -- fast.
I have some idea from my own awareness, but what does my genome say?
It is a profound time of personal discovery that has never been possible until now.
In previous times when people tried to know themselves they were not able
to have some objective readout that gave polygenic scores on every feature of their being.