We have Cannabis Whole Genome Sequencing honed to the point where people are using it to untangle the history of the famous Skunk #1 line.

I wasnt around then so I cant speak with any authority on the oral history but I can help people better understand Kannapedia.net
Phylo-Trees can be complicated so lets just take a look at the genetics of THCAS.
There are a few interesting mutations found in early cannabis lines that we will go over.
Ala250Asp
Pro333Arg
Pro542Leu
Ser355Asn
A recently sequenced Skunk line
kannapedia.net/strains/rsp124…
A250D and Pro333Arg are some of the most common mutations.
A250D is found in 12.7% of the NGS data. The C90 data finds this more frequently but less samples have been run through that pipeline.
P333R is found in 18.2% of the NGS data.

Click on the blue %Number
Kannapedia.net will bring up all of the strains (83) that share that THCAS mutation (P333R). Very helpful for sorting out the ancestry of just THCAS.

One can repeat this for A250D and get a list of 58 strains.
Kannapedia.net is a bit light on strains with Skunk in the name so don't take this as gospel trying to build a distributed consensus.

But of interest...
There is a Big Skunk from the Chinese Landrace study. Same THCAS as the JL reference
kannapedia.net/strains/srr147…
The most recent Skunk added to Kannapedia has different THCAS.
P542L. Only 1.8% of the sample have this mutation.
kannapedia.net/strains/rsp124…
8 other strains share this rare mutation. It is close to the end of the gene and its not clear what the function of this mutation is but in general Proline changes should be monitored.
kannapedia.net/strains?NGS=EF…
So other than using these variants as a mechanism to track ancestry, do any of the mutations play a role in THCA production?
It's not clear that individual mutations are having an impact. You must recall, there are at least 2 THCAS in every genome. P542L is heterozygous
A few samples in Kannapedia.net have this variant in a homozygous state. One is an old Hemp line (Tiborszallasie).
kannapedia.net/strains/rsp112…
Sour Tsunami is another one. kannapedia.net/strains/rsp111…
This also happens with A250D. Most strains are heterozygous but some are homozygous for the variant. kannapedia.net/strains/rsp111…
Why do these Homozygous variants matter?
When both copies of THCAS are impacted, their impact on expression is more obvious.
Have a look at CBG lines.
This is a common mutation we see in some CBG lines that knocks out THCAS activity. Often found with homozygous P333R & S355N
This can be seen in
kannapedia.net/strains/rsp114…
There are 8 other CBG strains that have a THCAS gene with these 2 missense mutations. This is rare. Most CBG lines have both CBDAS and THCAS completely deleted. Convergent evolution. Many ways to skin a cat (please don't skin cats).
Of note is the THCV line known as Doug's Varin.
That's odd, as THCV production needs a functional THCAS. But alas, its heterozygous for P333R and S355N. It has a functional THCAS but also a bunk copy of THCAS from CBG lines.
kannapedia.net/strains/rsp112…
In summary, the latest Skunk to enter Kannapedia.net is unique compared to the others but the database needs more Skunks to really draw any conclusions on ancestry. Tracking the THCAS variants alone can be very helpful.

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More from @Kevin_McKernan

Jan 17,
If you read the Corman Drosten retraction demand addendum, you will see we voice concerns over both FN and FPs.

A common newb retort is that the test can’t have both.
On an individual test this is true but on a population level this is false.

pubmed.ncbi.nlm.nih.gov/34741305/
So why do we only hear debate about the FP rate?

I believe this is because the implications of FPs are less severe than the implications of FNs.

FPs you can confirm with another test or just suck it up and quarantine for the ‘greater good’.
FNs, on the other hand, expose the entire track trace system as the scam that it is.

Particularly when they are this high.
Once negative, very few people want to stand in a line with other potentially sick people and pay $50-300 a second shot at quarantine.
Read 4 tweets
Jan 8,
Respiratory viruses have been around longer than any Judge. To assume parasitism and not mutualism is myopic.
45% of our genome consist of viral elements (LINE, Alu etc) and 8% of the genome consists of infectious retroviruses.

ncbi.nlm.nih.gov/labs/pmc/artic…

annualreviews.org/doi/abs/10.114…
Zero virus plans assume viruses that may be pathogenic for some age groups can be mutualistic for others.

ncbi.nlm.nih.gov/labs/pmc/artic…
The advent of NextGen sequencing allowed us to peer into mutualistic viruses, as in the past, expensive sequencing was reserved for exploring pathogens.

pnas.org/content/118/10…
Read 5 tweets
Jan 5,
An octogenarian in diapers is centrally planning 330M people’s health care with disastrous results…

Many citizens like it

Cheer it on

Even argue for more

Not because it is rational but because they need their tribe to form their identity.

Insecurity induced Munchausen’s.
Much talk about Ass Formation.

I prefer the moniker “Munchausen’s by internet”

ncbi.nlm.nih.gov/pmc/articles/P…
This is an interesting read on how Facebook performed a psychological experiment on 860K of its customers without an IRB.

What’s not to like about spreading massive-scale emotional contagion?

Can I get a side of spike protein with that?

pnas.org/content/111/24…
Read 5 tweets
Jan 1,
I like mice…
So does some lab that derived Omicron.

Very good read.
You’ll see how Molnupiravir could not have done this alone.
Random C->U mutations are not elevated in omicron but GC-AT are different in early omicron Vs post outbreak.
Mice host!

sciencedirect.com/science/articl…
GC-AT mutations are a signature of ROS damage that makes 8-OxoG.
ROS is elevated in febrile viral infections.

These authors looked at early omicron Vs post outbreak omicron and see a difference here suggesting omicron had a different host at some point.
Mice fit the bill.
Another kind cat sent me this paper.
Another important point is the Ka/Ks analysis they do (dN/dS).
This shows 6.6X higher selective pressure on spike but not on the rest of the SARs genome.
Mice + selection against spike (vax of MAbs) could do this.

Lab derived.
Read 6 tweets
Dec 29, 2021
Can't Find a C19 test?
Low supply, Fiat Demand...

I am shocked at how expensive these C19 tests are ($100-$300).

And no...The free ones are not free!

They are printing money, diluting yours and paying a heavy price you just can't see.

Diagnostic PCR is usually $30.
Even with 10X higher margins on C19 PCR, there are still droughts after 2 years?

Why?

This is the story of central planning where the market gets run by whimsical gov diktat and pricing signals are destroyed.

When pricing signals are destroyed companies dont know how to plan
Will Biden have an aneurism or an epiphany today and order 500M tests they fumble?

Will schools panic on Omicron and order more school testing of asympto kids who don't get sick?

When you run the market by Fiat, you create artificial demand but you don't create supply.
Read 5 tweets
Dec 29, 2021
I’m in the process of updating this for submission (2,000 downloads before submission)
Several details people have brought up in support of this.

Will walk through them.

osf.io/bcsa6/
1)Some folks at NIH reached out pointed out the work on ribosomal pausing that we missed.
It’s very relevant.

Just the codon change in the FCS is enough to pause the ribosomes and alter 3D structure of spike.
Just 2 codons!

mdpi.com/1422-0067/22/1…
They changed many codons.

2)pseudouridine and N1-methyl should be better spelled out. Xia et al conflates the two and we will spell this out more.
PseudoU wobbles more the methylpseudoU but both significantly alter Tm and thus are ‘stickier’ bases than disrupt translation.
Read 11 tweets

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