rs1129844 This story is so big... it deserves its own thread!

[BerniF]

Thanks J11 3 strawberry milkshakes coming up

My sister has just completed the 23& me test and we are going to compare also hoping to get my dad to test.

Where else could I get the snp rs1129844 genotyped now that 23&me don't include it?

[J11]

Extra Large!

Yeah, I suppose I got the short end of the stick on this trade.
Knowing that dementia might be delayed by 7 years is worth quite a bit more than 3 milkshakes.

This is great news about other family members getting onboard.
You could work the genetics through.

With your sister's genetics, you might be able to determine your mother's genotype at rs1129844.
If your father genotyped, you could use an online tool to do a quasi phasing.
You might also be able to locate some other near relatives.

Perhaps you could even try something similar to my idea of using 23andme to find more distant relatives
to narrow down where the dementia risk variant might be.

In terms of actually getting this genotyped I am at a loss. I went to http://www.broadinstitute.org/mpg/snap/ldsearch.php
and chose all of the gene chips for rs1129844. None of them reported it!

I have made an inquiry about a special BGI has announced about a $250 50x exome sequence offer. That might be one of the
better bets. However, in our loved one's 65x exome scan the rs1129844 SNP happens right near the end of an exon and only has 10x coverage. Even at this coverage level we got a passing heterozygote call. Yet, if I were you, I would love to have 100x coverage for the SNP. Sometimes with these scans if they can scrimp a bit, they do. Often, they will have one big pile up near the middle of the exon and the coverage tends to become minimal or non-existent at the ends.

I have also asked a sequencer about individual SNP typing. The bean counting was $60 setup fee for each marker, $30 per marker genotyping by sequencing at 2x coverage using bi-directional Sanger sequencing PCR amplified with forward and reverse primer and
$28 per sample for saliva extraction. 2x coverage seems fairly weak, though Sanger sequencing is something of a gold standard. So, sure paying over $100 for a single SNP seems completely ridiculous, probably soon be able to get the entire exome done at high uniform coverage for that price, though the eotaxin SNP does seem especially important.

[BerniF]

Thanks for taking a look J11, I think I'll wait until I can get the entire exome done.

[J11]

BernIf,

You should really think of giving Ancestry.com a try.
I am just so amazed at their product.

You can build your family tree with almost no effort going back at least into the 18th Century.
The last few centuries have been this golden age of record keeping.
It is just amazing!

The idea would be to build up your family tree, and then try and work out how the dementia
was inherited through your family. I am now very excited about the prospect of breaking through to find our family's
risk variant.

The one thing you need to know though, is that for some totally strange reason, Ancestry.com does not connect up the genetics for you.
If you do not genotype with them, they do not allow you to upload your 23andme results. FamilyTree.com, though, does allow uploading.

[J11]

Here's the results from the recently cited Nature article concerning age of onset of dementia among the Colombian PSEN1 mutant carriers.

{The good genotype is listed first and an estimate of the change in age of onset of AD is given as shown in Supplementary Table 3c.}

Nine mutations harbored in

APOE (rs7412, P=5.44 × 10−35), rs7412 T/C versus C/C 9.8 years
GPR20 (rs36092215, P=3.36 × 10−26), A/G versus G/G 7.5 years
TRIM22 (rs12364019, P=8.78 × 10−19), ? seems like there is 0 difference
FCRL5 (rs16838748, P=8.79 × 10−14), G/T versus G/G 7.2 years
AOAH (rs12701506, P=7.26 × 10−12), G/G and G/A versus A/A 5.9 years
PINLYP (rs2682585, P=2.55 × 10−10), A/A versus G/A and G/G 2.6 years
IFI16 (rs62621173, P=1.54 × 10−9), C/C versus C/T 4.6 years
RC3H1 (rs10798302, P=3.80 × 10−8), A/A versus A/G 1.3 years
DFNA5 (rs754554, P=8.32 × 10−6) T/T versus G/T and G/G 10.5 years

This shows us again how important lower prices for genomics technology would be for AD research.
Notice in Supplementary figure 3c that the age of onset information seems to be showing that there is yet more structure in these images that could have been further explored if the price for exome sequences etc. were lower. It would be very interesting to know how much of the variation in age of onset their final model was able to explain.

I really do not understand why this type of research was not done years ago. Knowing when you are likely to develop AD is every bit as important as if you are going to develop AD. There was a startling range of age of onset among the Colombian PSEN1 carriers. For some illness began in their early 30s, for others their 70s. That is a huge huge range! The CRISPR is brought to mind.

[J11]

I found this article interesting.
http://journals.plos.org/plosone/articl ... ne.0144898

I cannot think of any other article that has actually given genotypes for the subjects (see supplementary File S2 Table A).
In almost any Western country this would probably be illegal.

Yet, such disclosures could make for some interesting open access science.
Who knows what someone living in their parents basement might think up!

[hill dweller]

edit

[Stavia]

Love it hill dweller!
Thats kinda my attitude atm. The former not the latter.
Btw your name evokes a hobbit to me. I'm prolly totally wrong.

[J11]

Hill, don't worry when CRISPR comes online you can be whoever (whatever) you want to be whenever you want it!
You would decide your genotype.
Want to be APOE epsilon 3,3?
How about epsilon 3b,3b?

They have already built mice with a built-in CRISPR unit, all that's needed for them is the guide RNA and they live their dreams.
Fascinating!

[Gilgamesh]

3b/3b: J11, you're once again singing my tune!

Hill Dweller: There's a curious logical problem with "first to live forever". But that might not stop your husband. Myself, I have no interest in dying or getting seriously ill in the next few weeks or so. Can't imagine that, a few weeks or so from now, my attitude about the following few weeks or so will have changed (including not being able to imagine that, a few weeks or so beyond that...).

One of Aubrey de Grey's more entertaining videos about longevity:

https://www.youtube.com/watch?v=dt_fP3fCkNo

G