Genome Has Been Sequenced

[spurr]

@ mofeta,

How about they also sequence triploid and tetraploid chromotypes? That would be useful, no?

 

[bonbolos]

sequencing the genome in a haploid or in a tetraploid phase is striclty the same,you'll keep on having the same sequence, just more copies of it.

Having the whole genome using the shotgun technique is more or less useless, the technique being highly hazardous. what's the number of fold ? needs to be sufficiant to be sure the whole genome is actually there and there is enough overlaps.
once it will be sequenced with enough depth and enought individuals, it will be usefull for fundamental research

but for sure it is useless for molecular breeding !

cheers

 

[mofeta]

@ mofeta,

How about they also sequence triploid and tetraploid chromotypes? That would be useful, no?

What bonbolos said. Having more copies of the same thing doesn't help.

What you want is many sequences from many individuals, compare observable traits and their correlation with chunks of genome. A good example of this made the news today, in a story about a major advance in our understanding of motor neuron disease (ALS). The researchers compared the sequences of people from a family with hereditary ALS with those from people without it. They found several mutations that led to a defective protein. They then confirmed by finding the defective protein in autopsy tissues of ALS victims.

Having the whole genome using the shotgun technique is more or less useless, the technique being highly hazardous. what's the number of fold ? needs to be sufficiant to be sure the whole genome is actually there and there is enough overlaps.

I haven't actually looked at what Medical Genomics has posted to the cloud, but I don't think they used old-fashioned low-read number shotgun approach. McKernan is a leader in developing next-generation sequencing techniques that do many many reads of small fragments (producing massive overlap). This is much faster than old shotgun approach. McKernan's next-gen technique is called SOLiD for anyone who wants to Google it up.

once it will be sequenced with enough depth and enought individuals, it will be usefull for fundamental research

but for sure it is useless for molecular breeding !

Yeah this single sequence is of relatively little value to us. You could find genes that are homologues of well known genes in other plants, but the utility of this in breeding is limited (aside from identifying things like the centromere specific histone genes in Cannabis).

With the use of fast next generation techniques, the number of sequences should stack up quickly, and things will become clearer.

BTW, bonbolos, are you a non-native speaker of English? I find your choice of the word "hazardous" interesting.

 

[mofeta]

I failed to mention that they may look for markers to narrow down the parts of the chromosome that are of particular interest (linkage) for their association studies. Maybe not, though. The new techniques of mapping are massively parallel, and make the narrowing down of linkage less and less important (you can do association studies of the whole genome).

linkage = low res (chromosome region)

association = high res (allele)

EDIT: Linkage studies are also useless for traits that are controlled by alleles that aren't always found on the same chromosome region. Alleles that are far apart on the chromosome are more likely to be "shuffled" during meiosis (independent assortment). That's one of the reasons GWAS techniques are so powerful.

 

[mofeta]

Whoops, I just noticed this part right at the beginning, I guess I wasn't paying very close attention:

...and the sequencing was conducted by several service providers, including the latest long read technology from Roche’s 454 sequencing center.

I wondered why they used the competition's technology, so I looked into it and this is what I found:

McKernan says:

“With the goal to sequence multiple Cannabis varieties, we initially took the approach of using short-read next generation sequencing technology on the C. sativa strain. We very quickly realized that this method was not going to provide a clear picture of the genome required to tease out the important biological pathways. This realization caused somewhat of a paradigm shift in the way we approached this project. At this point we moved to triple backcrossed cultivars and longer read technology.”

More:

Surprised in part by the finding that genomic variation between Cannabis strains is over 1%, a figure that is 10 times the variation of human genomes, the team at Medicinal Genomics turned to Roche’s 454 Sequencing Center in Branford, Connecticut to sequence the Cannabis indica strain on Roche’s new GS FLX+ System, the latest advance in long read next generation technology. The researchers obtained roughly 18x genome coverage with the 700-800 base pair long reads, enabling a high-quality draft assembly of this complex plant genome.

“I was stunned by the data quality and more impressively the read lengths of the data coming off the GS FLX+ Instruments,” said McKernan. “With the long reads we can sort out the variation in the strain and phase alleles so that we can make biological sense of the sequencing data. We can assemble some key synthase genes into much longer phased blocks, allowing us to focus more on the biology and less on the computational concerns over collapsed polymorphic assemblies we were seeing with the shorter read systems.”

The fact that one of their competitors had to turn to Roche for the technology to do their project made them very happy:

“We are pleased to see an industry-renowned expert in the field of next generation sequencing recognize the value of the long reads offered with our new GS FLX+ System,” said Todd Arnold, Vice President of Development at 454 Life Sciences, a Roche Company. “This project, along with other work on a variety of large plant and animal genomes, confirms the power of long reads for high-quality assembly and, most importantly, for correlating sequence content with biological significance.”

This bit is interesting also:

...pathways can be optimized in the plant or cloned into other hosts for more efficient biologic production. In addition, it may be possible through genome directed breeding to attenuate the psychoactive effects of Cannabis while enhancing the medicinal aspects.

Info from Roche press release 8/18:

Medicinal Genomics Sequences the Cannabis Genome Using Roche's GS FLX+ System

 

[mofeta]

Here is the data on the elastic beanstalk

Highlights:

• 327x coverage!
• they haven't run it through Celera (open source assembler on Source Forge)
• "The C. sativa strain is more polymorphic than the C. indica strain currently being assembled"
• they already have some contig chunks

This whole thing is blowing my mind! Cannabis is on its way to being one of the best understood organisms! The only other living things that have received as much scrutiny are humans and model organisms like Arabidopsis and Drosophila!

I almost can't believe it.

 

[mofeta]

Any body here own or have access to an 64-bit x86 linux/unix box with >128Gb ram?

 

[guineapig]

Yes this is an important event I would like to say good work to all the scientists involved...

The non-psychoactive cannabinoids I would like to thank you too....

kind regards from guineapig

 

[bonbolos]

cheers for the info, very interesting.

my bad about the shot gun tech, it seems a bit weird they used this old tech i realize now. molecular engeniring is not my speciality!

BTW, bonbolos, are you a non-native speaker of English? I find your choice of the word "hazardous" interesting.

yeap, indeed, misuse of the word.

anyway with such a sequencing (18x genome coverage !) there are many things to do. there is already a little EST library from cannabis transcripts with many genes from the cannabinoid pathway such as polyketide synthases and such (Identification of candidate genes affecting Δ9-tetrahydrocannabinol biosynthesis in Cannabis sativa, MD Marks et al.)

what i would like to see is snp makers liked to phenotypes found by studying interesting segregant crosses (indica x sativa). this would be a real breakthrough for breeding. Need somebody with enough space to grow enough plant and with DNA techs, not yet to be..

This whole thing is blowing my mind! Cannabis is on its way to being one of the best understood organisms! The only other living things that have received as much scrutiny are humans and model organisms like Arabidopsis and Drosophila!

yeah and the 20 most important food crops (rize, corn, wheat, cannola, sugar beat etc etc) !

thanks again for the info and the links, quite impressive !

cheers

bonbolos

 

[GL_Guerilla]

whoa, hold your horses everyone...
doesnt anyone else think this may also be a very BAD thing?
this will give big pharma the opportunity to develop cannibinoid based drugs
that DONT get you high...that are all patented by the drug companies...
the FDA will approve it, and those drugs wont be schedule 1, but cannabis by itself still will be illegal as hell, no accepted med value....while there will be a slew of cannabis-based pharma pills that dont get you high.... that arent even scheduled...
this information in the wrong hands will be deadly.
big pharma and the gov't are about take the "medical" out of "medical marijuana"...
or am i paranoid?

 

[pineolene]

whoa, hold your horses everyone...
doesnt anyone else think this may also be a very BAD thing?
this will give big pharma the opportunity to develop cannibinoid based drugs
that DONT get you high...that are all patented by the drug companies...
the FDA will approve it, and those drugs wont be schedule 1, but cannabis by itself still will be illegal as hell, no accepted med value....while there will be a slew of cannabis-based pharma pills that dont get you high.... that arent even scheduled...
this information in the wrong hands will be deadly.
big pharma and the gov't are about take the "medical" out of "medical marijuana"...
or am i paranoid?

cannabis based drugs that DON'T get you high are EXACTLY what modern medicine needs. there are so many medicinal compounds in this plant that can/should be isolated. Old sick people just want to get healed, not high. deadly? are you on drugs? making medicine from cannabis that doesn't get you high is healing, not deadly.

is there something wrong with making medicine from cannabis? would you prefer people stay sick and big pharma/govt do nothing?

 

[GL_Guerilla]

The plant should be used as a whole, the same reason marinol doesnt work will be the same reason why these other cannabinoid drugs probably wont work as intended, or perhaps have side effects...we dont understand the complex relationship between all the cannabinoids in this plant....therefore, i doubt isolating any one cannabinoid will work as intended.

and that's not really the issue I have,
the issue I have is that they will legalize these cannabinoid based drugs, while the plant on a whole, will probably remain illegal, sched.1...

 

[pineolene]

The plant should be used as a whole, the same reason marinol doesnt work will be the same reason why these other cannabinoid drugs probably wont work as intended, or perhaps have side effects...we dont understand the complex relationship between all the cannabinoids in this plant....therefore, i doubt isolating any one cannabinoid will work as intended.

and that's not really the issue I have,
the issue I have is that they will legalize these cannabinoid based drugs, while the plant on a whole, will probably remain illegal, sched.1...

YOU may not understand biochemistry... but that doesn't mean educated professionals don't understand biochemistry. By comprehending the genome "we" can breed strains that lack THC, making it possible to heal people without getting them high, aka making medicine. Your doubt isn't even based on this, you are worried about chemical extraction of single compounds. I am talking about whole plant extracts that lack THC. Do you see the gigantic difference?

So you would prefer to hold back cannabis based medicine for everyone because federally we can't smoke pot legally? Seems pretty selfish and immature to me. Don't you think medicine comes before recreation? You know you can move to one of the many medical marijuana states and help yourself out.

 

[OLDproLg]

COOL!!!!!

the more our plant becomes more an more popular
the more it will be excepted,i hope people find cures!

 

[quitelost]

Thought many common hemp strains have very high CBD and low THC? Is CBD not the one of the cannabinoids with the most accepted medical value? I still don't understand why these hemp stains, arn't more widely studied, they are legal in much of the world. Possible because they can't be patented.

I think this is an interesting development but GL_Guerilla has a point in my opinion, genetic science and engineering is highly under-regulated. Studies like this open up the possibility for private pharma firms to patent cannabinoid strains or preparations and continue to support the oppression of those whom wish to grow their own meds or produce medicine on a smaller scale. Cannabis and cannabis based drugs have been used for more than 6000 years as medicine, bred by thousands of different people from different cultures. Personally don't think its right for big pharma to patent these preparations and sell them to the sick for $1000+ a month and I believe companies such as GW pharma are already doing this.

I didn't see anyone in this thread suggesting that investigating cannabis or cannabinoids is bad in itself. It's just that big pharma has a very spotty history to say the least, especially in the case of medical ganja. I don't think its fair to flame GL_Guerilla for mentioning this when he was just trying to bring another perspective to the discussion.

However I disagree with his claim that cannabis should only be used as a whole. This idea of whole or nothing is a perspective shared by many herbalists and practitioners of traditional medicine probably because even with modern techniques its extremely hard to replicate the synergy of compounds in these natural medicines.

This study and others like it are important, hope we can continue to express our opinions and knowledge regarding this without personal attacks...

 

[quitelost]

Furthermore cannabis is already a safe medicine used by millions that are forced to consume black-market, commercial quality garbage including in dutch coffeeshops and U.S. medical dispensaries. I personally know of many people whom benefit from cannabis as a medicine but are scared of excessive and dangerous police tactics, judicial sanction, discrimination, black-market prices and low quality. Not to mention the countless mildly ill to chronically ill to critically ill or persons with disability’s whom confront this reality everyday as they self medicate under prohibition.


Does the average medical user anywhere in the world knows what pesticides and herbicides were applied to the product they're consuming or what is mixed into the different batches of commercial hash many people consume? I think not because there is no transparency or regulation.

If history tells us anything big pharma is going to, lobby to kill all competition, patent everything it can and push prices sky-high. In this game big pharma's largest competitor is the medical cannabis industry. None of these other cannabinoids have been studied as well in humans as THC and CBD which are in all cannabis. I'm under the belief that the endocannabinoid system is not very well studied or understood.

Cannabis is a treatment that is safe, effective for millions and has been used for Millenia. it is well studied, cheap and easy to grow almost anywhere. It is probable these firms are going to charge extremely excessive prices until the patent runs out. Plus attack medical cannabis, as they have for years, but with more fervor than ever-before to protect their new brands. 15% of the U.S. is impoverished not everyone can just “move to Cali man” or pay these insane prices from blackmarketters or Pharma. I live outside the U.S. as do most medical users.

How can we expect Big Pharma to do adequate study on these cannabinoids before rushing them to market if they don't do so with other drugs? Who knows what the long term affects of these other cannabinoids could be at higher concentrations than those in cannabis or outside the synergistic equilibrium of natural cannabis?

 

[GreenintheThumb]

Thought many common hemp strains have very high CBD and low THC? Is CBD not the one of the cannabinoids with the most accepted medical value? I still don't understand why these hemp stains, arn't more widely studied, they are legal in much of the world. Possible because they can't be patented.

They can be patented...

I think this is an interesting development but GL_Guerilla has a point in my opinion, genetic science and engineering is highly under-regulated.

GMO is pretty damn highly regulated in my country...

Studies like this open up the possibility for private pharma firms to patent cannabinoid strains or preparations and continue to support the oppression of those whom wish to grow their own meds or produce medicine on a smaller scale. Cannabis and cannabis based drugs have been used for more than 6000 years as medicine, bred by thousands of different people from different cultures. Personally don't think its right for big pharma to patent these preparations and sell them to the sick for $1000+ a month and I believe companies such as GW pharma are already doing this.

Most medical patients end up spending $1000+ for herbal cannabis a month and all that money goes into someone's pockets. Someone who did no real work or any R&D that I can see unlike GW pharma.

However I disagree with his claim that cannabis should only be used as a whole. This idea of whole or nothing is a perspective shared by many herbalists and practitioners of traditional medicine probably because even with modern techniques its extremely hard to replicate the synergy of compounds in these natural medicines.

And as science is able to investigate and unravel the synergistic compounds it'll get easier and easier. This genomic data will further progress. I'm sorry but my sick grandma doesn't want to smoke the Afghani you grew in your dirty basement that you claim is high in CBD.

I think overall this is starting to get off topic.

 

[overgrow00]

So you would prefer to hold back cannabis based medicine for everyone because federally we can't smoke pot legally? Seems pretty selfish and immature to me. Don't you think medicine comes before recreation? You know you can move to one of the many medical marijuana states and help yourself out.

wait a sec...

getting high is medicine to some of us, not just recreation...

besides you can argue it the same both ways. Millions locked up, families suffering, because if will never be legalized... or hundreds of thousands suffering from the need to get high to often... it can go both ways, really... Might seem pretty selfish and immature to some, that somebody would rather allow cannabis to remain illegal just so they can be healed without the side effect of "getting high"...

just think about it from outside the box first...

 

[quitelost]

I think overall this is starting to get off topic.

Much of this thread,discounting the scientific jargon, was members clamoring over the potential good of this and you didn't say anything. Some strong opinions about medical cannabis and herbal medicine were left here for weeks and I think people should*be able to*respond. Plus the original article you posted is in my opinion quite unbalanced regarding medical cannabis. Seems that this text could leave readers with the idea that Pharma has the only answer, there are many questionable quotes I could pull but I will leave others to read and decide for themselves . When others arrive with a different opinion it's "off topic"?

GMO is pretty damn highly regulated in my country...

Many would say the same about where I live but when talking to those involved in agribusiness one finds that this really is not the case.
How regulated is GMO use for feed? GMO testing on plants and animals? GMO imports?Are farmers required to grow sterile crops or are GMO genetics polluting traditional strains in your country? Even if they're sterile what prevents pathogens and other factors from spreading these genetics?What prevents pollen from crossing your borders? What prevents people from ordering GMO on the net and receiving seeds in the mail? I can't clearly respond to your claims without knowing where you live and frankly I'm not interested because I'm not talking about “ your country” we live in a globalized world today.

Most medical patients end up spending $1000+ for herbal cannabis a month and all that money goes into someone's pockets.

You really want me to believe that the majority of medical cannabis users internationally pay more than 700e monthly? I know medical patients in some of the most expensive markets in the world whom don't pay that much, not to mention those in the 3rd world. Also I am here supporting legalization not the black-market that created the high prices.

Someone who did no real work or any R&D that I can see unlike GW pharma.

I don't need to do R&D to know medical cannabis works for millions, much of the research is already out there. I don't need much to locate a hemp strain, pure CBD sample, and a sympathetic Uni student or professor to do some chromatography. I don't need R&D to preform simple extractions of these hemp stains that would result in a extract with very high CBD content. One could then mix this with high quality herbal cannabis or hash at different ratios and the result would be something very similar to a generic version of the GW pharma product at a fraction of the cost.

I'm sorry but my sick grandma doesn't want to smoke the Afghani you grew in your dirty basement that you claim is high in CBD.

When my grandmother was dieing from cancer she received a “conventional” medical treatment in tandem with a traditional medical treatment, her cancer went into remission for years. Which treatment was more effective I do not know. I just believe that all patients like my grandmother should have option to what treatments they want to undergo whether it pertains to herbal medicine/traditional medicine, physical therapy, osteopathic medicine and “conventional" medicine or some combination.

Also I never made any claims about the CBD content of the pakistani strains and crosses I may or may not posses. I don't know where you read this in my writings as the only strains I mentioned in regard to CBD were hemp strains, far from the classic drug cultivars you seem to be bringing up.

They can be patented...

True and I will edit my original post shortly to correct this.


No one has adressed many of the points raised by myself and other members; that cannabis works for millions, that millions face violence and judicial sanction medicating with cannabis, that Pharma has and will continue to attack medical cannabis as they have for decades due to the competition they see in it, that none of the other cannabinoids in cannabis outside of THC/CBD have been sufficiently tested a medically effective doses in humans, that Pharma may rush these products to the market without decent trial as they continually do with their products, that patients have the right to select the type of treatments they feel are effective for them, that the majority of medical users don't qualify for existing products, that the majority of patients can't afford these products, that these drugs are being sold a replacement for cannabis when none has yet come close to this, that people should be able to grow their own meds no matter what and everywhere,.


GreenintheThumb please edit the part of your post that paints me as a sleazy cannabis pimp who wants to push drugs of suspect quality to your grandmother, this was really unjustified.

 

[GreenintheThumb]

Much of this thread,discounting the scientific jargon, was members clamoring over the potential good of this and you didn't say anything. Some strong opinions about medical cannabis and herbal medicine were left here for weeks and I think people should*be able to*respond. Plus the original article you posted is in my opinion quite unbalanced regarding medical cannabis. Seems that this text could leave readers with the idea that Pharma has the only answer, there are many questionable quotes I could pull but I will leave others to read and decide for themselves . When others arrive with a different opinion it's "off topic"?

You're free to your own opinion my friend. I'm not trying to silence you. But I started this thread to speak on genomics, something you aren't touching on with all your anti-pharma talk that I really just don't care about. Start a Big Pharm Is Evil and Going To Patent everything thread if you wish.

Many would say the same about where I live but when talking to those involved in agribusiness one finds that this really is not the case.
How regulated is GMO use for feed? GMO testing on plants and animals? GMO imports?Are farmers required to grow sterile crops or are GMO genetics polluting traditional strains in your country? Even if they're sterile what prevents pathogens and other factors from spreading these genetics?What prevents pollen from crossing your borders? What prevents people from ordering GMO on the net and receiving seeds in the mail? I can't clearly respond to your claims without knowing where you live and frankly I'm not interested because I'm not talking about “ your country” we live in a globalized world today.

Oh...maybe it's an anti-GMO thread you should start?

You really want me to believe that the majority of medical cannabis users internationally pay more than 700e monthly? I know medical patients in some of the most expensive markets in the world whom don't pay that much, not to mention those in the 3rd world. Also I am here supporting legalization not the black-market that created the high prices.

I live in a medical state and the truly sick people still spend that much...don't know what to tell you. The overpriced herb annoys me about as much as the overpriced meds from big pharma.

I don't need to do R&D to know medical cannabis works for millions, much of the research is already out there. I don't need much to locate a hemp strain, pure CBD sample, and a sympathetic Uni student or professor to do some chromatography. I don't need R&D to preform simple extractions of these hemp stains that would result in a extract with very high CBD content. One could then mix this with high quality herbal cannabis or hash at different ratios and the result would be something very similar to a generic version of the GW pharma product at a fraction of the cost.

Sounds like a little R&D project to me...

When my grandmother was dieing from cancer she received a “conventional” medical treatment in tandem with a traditional medical treatment, her cancer went into remission for years. Which treatment was more effective I do not know. I just believe that all patients like my grandmother should have option to what treatments they want to undergo whether it pertains to herbal medicine/traditional medicine, physical therapy, osteopathic medicine and “conventional" medicine or some combination.

Agreed, my point was that many grandmas are weary of herbal medicine that lacks standards...there's a useful piece of the market for "big pharma" to go after and it isn't going to be the death of our favorite herb.

Also I never made any claims about the CBD content of the pakistani strains and crosses I may or may not posses. I don't know where you read this in my writings as the only strains I mentioned in regard to CBD were hemp strains, far from the classic drug cultivars you seem to be bringing up.

My friend I don't know who you are and haven't read any of your other posts and was completely unaware of your pakistani cultivars.

No one has adressed many of the points raised by myself and other members; that cannabis works for millions, that millions face violence and judicial sanction medicating with cannabis, that Pharma has and will continue to attack medical cannabis as they have for decades due to the competition they see in it, that none of the other cannabinoids in cannabis outside of THC/CBD have been sufficiently tested a medically effective doses in humans, that Pharma may rush these products to the market without decent trial as they continually do with their products, that patients have the right to select the type of treatments they feel are effective for them, that the majority of medical users don't qualify for existing products, that the majority of patients can't afford these products, that these drugs are being sold a replacement for cannabis when none has yet come close to this, that people should be able to grow their own meds no matter what and everywhere,.

I came here to talk about genomics and the potential wealth of information there...again much of this seems off topic.

GreenintheThumb please edit the part of your post that paints me as a sleazy cannabis pimp who wants to push drugs of suspect quality to your grandmother, this was really unjustified.

Just trying to get my point across and state that true pharmaceuticals have their place and would help people.

Now back to bioinformatics and genomics please!