And so on and so forth! ... an interesting read!Yet, the more genomes researchers study, the more evidence mounts that using DNA to predict health risks is anything but precise – for now, at least. These days, nature's longest thread comes off a like a trickster, shape-shifting from person to person, written in a wily language no one fully understands, with at least three billion ways to misread it.
To try to bridge the chasm between reading and comprehension, scientists leading Canada's Personal Genome Project say they have taken the deepest dive possible into human DNA, conducting the most thorough analysis that current computing allows on the whole genome sequences of 56 Canadians who agreed to take part in the unusual and continuing experiment. Their report is published today in the Canadian Medical Association Journal.
Launched publicly in Canada in 2012, the PGP aims to build an open, online database of Canadian genomes for use by researchers anywhere and more than 1,100 Canadians have signed up so far. But by unravelling the entire codes of just the inaugural participants, what the project leaders have found is both promising and perplexing: medically relevant information in each volunteer, but also a vast trove of mysterious quirks and dramatic glitches that none of them expected to see in a cohort of healthy people.
Surprising, too, is that many of the volunteers carry mutated genes that suggest they should be sick, diseased or even near death – but aren't.
Take Participant No. 16, whose genes seem to tell the grim story of an aortic stenosis. The potentially lethal heart defect develops before birth, narrowing the body's main artery just above the valve that connects it to the heart, forcing it to work harder, which can lead to chest pains, heart failure and the risk of sudden death. On paper, No. 16 looks like a time bomb. In real life, he is a healthy 67-year-old who works long hours, skis, trains with CrossFit three times a week and, according to a CT scan, has a normal heart.
Participant No. 27 is another jolt. Missing from about 70 per cent of her blood cells is an entire chromosome, the X sex chromosome, of which women usually have two copies. On paper, No. 27 has mosaic Turner syndrome, a rare disorder that only affects females and can lead to impaired sexual development, short stature, a webbed neck and heart problems. In reality, she is a healthy 54-year-old who had no inkling her DNA harboured such a twist.
Cracks in the code: Why mapping your DNA may be less reliable than you think
Cracks in the code: Why mapping your DNA may be less reliable than you think
Cracks in the code: Why mapping your DNA may be less reliable than you think
ApoE 3/4 > Thanks in advance for any responses made to my posts.
Re: Cracks in the code: Why mapping your DNA may be less reliable than you think
Look forward to reading this, but certainly suggests lifestyle and environment have a big role in any disease.Surprising, too, is that many of the volunteers carry mutated genes that suggest they should be sick, diseased or even near death – but aren't.
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Re: Cracks in the code: Why mapping your DNA may be less reliable than you think
SusanJ wrote:Look forward to reading this, but certainly suggests lifestyle and environment have a big role in any disease.Surprising, too, is that many of the volunteers carry mutated genes that suggest they should be sick, diseased or even near death – but aren't.
Yes, i found it interesting too.
Re: Cracks in the code: Why mapping your DNA may be less reliable than you think
I actually just skimmed it a while back and would like to re-read it, but I think some of the examples they discuss weren't necessarily things that lifestyle impacts. Environment probably, whether that’s additional genetics or something else. Then of course other things like ApoE4 are influenced by both lifestyle and environment.SusanJ wrote:Look forward to reading this, but certainly suggests lifestyle and environment have a big role in any disease.Surprising, too, is that many of the volunteers carry mutated genes that suggest they should be sick, diseased or even near death – but aren't.
Last edited by circular on Fri Feb 23, 2018 10:27 pm, edited 1 time in total.
ApoE 3/4 > Thanks in advance for any responses made to my posts.
Re: Cracks in the code: Why mapping your DNA may be less reliable than you think
Fascinating. I recently became aware of Flossies (Fabulous Ladies Over Seventy) The project from Color is looking at genetic variants in women who have reached 70 without cancer. These are reported as variants of unknown significance which is not reassuring to anybody. http://whi.color.com/Now
Re: Cracks in the code: Why mapping your DNA may be less reliable than you think
circ, this is unfair!
You know how my mind works so well that you knew that this topic would magnetically attract me here.
It's almost like I'm part of your psychops project.
It is like honey for Pooh Bear, or cookies for the Cookie Monster or numbers for Count von Count!
{Am I the only one slightly disturbed by the current generation's lack of more edifying cultural reference points?}
Don't get me started!
Yet, when I read through the article you linked it is hard not to.
Has Canada actually not started a reasonably scaled Biobank project?
That is almost too difficult to imagine!
The Canadian scientific and sociopoliticoeconomic elites are not talking to each other!
It is best not to publicly display such lack of co-ordinations because in the modern
world others need to be sure that rational self-interested behavior is the norm and not the exception.
Not behaving reasonably in one respect increases the perceived risk that other behaviors will
also not be reasonable.
Any nation without a GWAS Biobank on the scale of (at a bare minimum) 1 per 1000 population (preferably closer to 1 per 100 population) can hardly be understood to be modern in any meaningful sense. As the article noted Canada
desperately needs to amp up ("on steroids") the reported scale of what was reported. That is obviously true.
The rate of return on such investment is simply too compelling not to establish such Biobanks.
As a personal example, I was able to find a disease causing variant in my family's exome file
simply through intuition.
I contacted an extended relative who shared a 10 cM match that included a variant in a gene of
known importance for a condition. What are the chances that they also shared this rarish condition?
1 in 300? Of course there are two strands, so perhaps half of that?
Yep, they also shared this rare trait; as do many others in our extended family.
It is fairly amazing. Entire hospitals could close from selecting against this one variant.
I would tend to think that the global heath care system on this variant alone would probably
save tens of millions of dollars per year (minimum) forever. Not bothering to invest the money
in such research would make it the worst possible investment decision (even by government standards!)
since tulips were in vogue. I think the logic should be fairly obvious: Surely, you can't criticize someone for
not doing something. YES, you can!
What is the rate of return on investment for that? I created tens of millions of dollars
of value for eternity without any actual hard cash outlay?
It's almost like I have my own printing press for money!
This one finding alone would financially justify a national biobank program!
There you go circ, there's a million for you!
I just do not know what I could possibly do with all this overflowing wealth and abundance that I have created!
I would encourage anyone else with a family history of some trait/illness of interest to do likewise.
While some more seasoned readers will be all to familiar with my monumental and admittedly epically
unsuccessful attempt to resolve my family's AD genetics, it should be noted that some traits such as
dementia, many commonly occurring cancers, forms of typical heart disease etc. are so highly
prevalent that unraveling the genetics of them in specific pedigrees is likely beyond the
scope of an individual family genetics project. Everyone develops Alzheimer pathology by age 90!
How could the specific family risk stand out from all that noise?
However, any clearly distinct family characteristic should, one might typically expect, allow for rapid isolation of the genetic
cause as occurred in the example I have cited above. Finding such variants should become all the easier as platforms
allow for surveying those within extended families. It is very difficult to imagine that this has not effectively happened yet with the
existing databases. Simple family surveys on Gedmatch Ancestry.com or 23andme would allow for nearly immediate finding of
family specific gene-trait connection. Why hasn't this been done? Using the 23andme database instead to find GWAS variants
of common but minute effect seems a hopelessly flawed strategy. The variants that will have large effects will be found within
extended families.
For a national Biobank, Probably enriching the sample with those who were substantially older than average would make a great deal of sense as might including those who were more burdened with various traits and conditions. In fact, the
non-APOE4 AD community and more broadly the clearly "differently normal" category would probably be one of the best to enrich for.
The traits present in the non-APOE4 AD side of our family are quite remarkable. It seems that we have almost every weird thing out there. I suspect there are doctors who are unaware of some of the things that are going on genetically in my family. The idea here is
that over the last several millennia many fairly odd people have been attracted into my family while the more normal
types who just wanted to quietly live their lives have formed another mating population. Strangely, the abnormal traits
that I refer also includes the Clotho intelligence allele. Interesting ideas just make life too complicated (for some).
This probably should give us all pause before we begin the era of human genetic re-engineering:
Up until this time the people who have likely been the drivers of innovative social and technological change are more than likely the same people who were genetically programmed to do more with their lives than live quietly. A similar observation has been suggested more broadly for the APOE4 community.
You know how my mind works so well that you knew that this topic would magnetically attract me here.
It's almost like I'm part of your psychops project.
It is like honey for Pooh Bear, or cookies for the Cookie Monster or numbers for Count von Count!
{Am I the only one slightly disturbed by the current generation's lack of more edifying cultural reference points?}
Don't get me started!
Yet, when I read through the article you linked it is hard not to.
Has Canada actually not started a reasonably scaled Biobank project?
That is almost too difficult to imagine!
The Canadian scientific and sociopoliticoeconomic elites are not talking to each other!
It is best not to publicly display such lack of co-ordinations because in the modern
world others need to be sure that rational self-interested behavior is the norm and not the exception.
Not behaving reasonably in one respect increases the perceived risk that other behaviors will
also not be reasonable.
Any nation without a GWAS Biobank on the scale of (at a bare minimum) 1 per 1000 population (preferably closer to 1 per 100 population) can hardly be understood to be modern in any meaningful sense. As the article noted Canada
desperately needs to amp up ("on steroids") the reported scale of what was reported. That is obviously true.
The rate of return on such investment is simply too compelling not to establish such Biobanks.
As a personal example, I was able to find a disease causing variant in my family's exome file
simply through intuition.
I contacted an extended relative who shared a 10 cM match that included a variant in a gene of
known importance for a condition. What are the chances that they also shared this rarish condition?
1 in 300? Of course there are two strands, so perhaps half of that?
Yep, they also shared this rare trait; as do many others in our extended family.
It is fairly amazing. Entire hospitals could close from selecting against this one variant.
I would tend to think that the global heath care system on this variant alone would probably
save tens of millions of dollars per year (minimum) forever. Not bothering to invest the money
in such research would make it the worst possible investment decision (even by government standards!)
since tulips were in vogue. I think the logic should be fairly obvious: Surely, you can't criticize someone for
not doing something. YES, you can!
What is the rate of return on investment for that? I created tens of millions of dollars
of value for eternity without any actual hard cash outlay?
It's almost like I have my own printing press for money!
This one finding alone would financially justify a national biobank program!
There you go circ, there's a million for you!
I just do not know what I could possibly do with all this overflowing wealth and abundance that I have created!
I would encourage anyone else with a family history of some trait/illness of interest to do likewise.
While some more seasoned readers will be all to familiar with my monumental and admittedly epically
unsuccessful attempt to resolve my family's AD genetics, it should be noted that some traits such as
dementia, many commonly occurring cancers, forms of typical heart disease etc. are so highly
prevalent that unraveling the genetics of them in specific pedigrees is likely beyond the
scope of an individual family genetics project. Everyone develops Alzheimer pathology by age 90!
How could the specific family risk stand out from all that noise?
However, any clearly distinct family characteristic should, one might typically expect, allow for rapid isolation of the genetic
cause as occurred in the example I have cited above. Finding such variants should become all the easier as platforms
allow for surveying those within extended families. It is very difficult to imagine that this has not effectively happened yet with the
existing databases. Simple family surveys on Gedmatch Ancestry.com or 23andme would allow for nearly immediate finding of
family specific gene-trait connection. Why hasn't this been done? Using the 23andme database instead to find GWAS variants
of common but minute effect seems a hopelessly flawed strategy. The variants that will have large effects will be found within
extended families.
For a national Biobank, Probably enriching the sample with those who were substantially older than average would make a great deal of sense as might including those who were more burdened with various traits and conditions. In fact, the
non-APOE4 AD community and more broadly the clearly "differently normal" category would probably be one of the best to enrich for.
The traits present in the non-APOE4 AD side of our family are quite remarkable. It seems that we have almost every weird thing out there. I suspect there are doctors who are unaware of some of the things that are going on genetically in my family. The idea here is
that over the last several millennia many fairly odd people have been attracted into my family while the more normal
types who just wanted to quietly live their lives have formed another mating population. Strangely, the abnormal traits
that I refer also includes the Clotho intelligence allele. Interesting ideas just make life too complicated (for some).
This probably should give us all pause before we begin the era of human genetic re-engineering:
Up until this time the people who have likely been the drivers of innovative social and technological change are more than likely the same people who were genetically programmed to do more with their lives than live quietly. A similar observation has been suggested more broadly for the APOE4 community.