Karen Miga Fills In the Missing Pieces of Our Genome

[Alvin2]

Karen Miga Fills In the Missing Pieces of Our Genome

Driven by her fascination with highly repetitive, hard-to-read parts of our DNA, Karen Miga led a coalition of researchers to finish sequencing the human genome after almost two decades.

In 1990, an international team of scientists began an ambitious attempt to sequence the human genome. By 2001 the Human Genome Project (HGP) had prepared a rough draft, and in April 2003, the draft sequence was declared finished. But Karen Miga, a geneticist now at the University of California, Santa Cruz and the associate director of the UCSC Genomics Institute, knew that while the work might have wrapped up, the sequencing was far from complete.

When the draft genome was published in 2001, how much was actually finished?

The very first draft sequence was an incredible resource, but it intentionally ignored the more complex, densely repetitive regions of our genome. Later efforts to get to a more finished state had about 8-10% still missing, and we kept hitting a technological wall to reach completion. In part this was due challenges in sequencing the repeats, but it is important to remember that even if the sequencing was perfect, we would still be faced with the obstacle of correctly putting those pieces together.


I feel like I am one of a small group of scientists who have been standing on our soapboxes for many years, saying, “Hey, our current maps are incomplete, and completing our maps will be important to our understanding of genome biology.” I suspect that many will be surprised to learn this, due to the very public celebration of the “finished” human genome in 2003. We were celebrating the completion of the parts of our genome that were technologically feasible at the time. It wasn’t really clear to the public how much of our genome was left unresolved and unexplored.

So it’s not like the T2T preprint genome is just topping off the previous human genome reference with a last few details. It’s more like there’s a whole chunk of our genome that operates in a different way just becoming available to us, and we have only begun to scratch the surface of that. The next 10 years should be very exciting, and I look forward to the future discoveries in these newly revealed regions.

https://www.quantamagazine.org/karen-miga-fills-in-the-missing-pieces-of-our-genome-20210908

 

[Alvin2]

I wonder if there will be any ME implications.
And if so how do we figure that out?

 

[Inara]

I think in research there is widely knowledge about "missing gaps" in the human genome data that we have today, at least that is my impression. I was regularly told that "we can only find what we know with today's technology, so we might miss sth.", or "we can't say, maybe we know in 5 years". That our understanding of DNA is incomplete is sth. I also regularly hear in the periodic paralysis field, where ca. 30% of patients have no known mutation. 30% is pretty much.

 

[Alvin2]

I think in research there is widely knowledge about "missing gaps" in the human genome data that we have today, at least that is my impression. I was regularly told that "we can only find what we know with today's technology, so we might miss sth.", or "we can't say, maybe we know in 5 years". That our understanding of DNA is incomplete is sth. I also regularly hear in the periodic paralysis field, where ca. 30% of patients have no known mutation. 30% is pretty much.

30% is almost 1 in 3

I recall Dr Davis saying they didn't find any specific mutation that causes ME, though that tryptophan bit they are working on is found in 75%(?) of the population but only 1-2% get ME.

I did post about this in the ask Dr Davis thread but if @Janet Dafoe doesn't respond perhaps we need to contact Dr Miga ourselves?
Though i am not up to this, can anyone else take it on?

 

[Hip]

I wonder if this relates to the RCCX Genetic Module Theory? The RCCX region of the human genome is a largely unexplored area. Some info is found in this post.



Though some historical context is necessary when trying to looking at possible genetic factors behind chronic diseases:

The rationale for undertaking the expensive human genome project (the project to map out the human genome) was that it was believed genes would explain all nearly human diseases. Whether it was heart diseases, cancers, neurological illnesses or immunological disorders, it was thought at the time that genetic factors were the likely cause.

The human genome project was finally completed in 2003. Unfortunately after its completion, it was soon realized that genetic factors were NOT the long sought after causal explanation of all the chronic diseases that afflict humanity.

Billions had been spent on the human genome project in the hope of understanding why diseases appear, but from the disease perspective, the human genome project turned out to be an expensive fiasco. Of course, it's great that we do have the human genome mapped (or at least mostly mapped), but it has taught us very little about the causes of chronic disease. It has turned out that genes are NOT the main causal explanation for chronic diseases, although genes may play a role.

So it is back to the drawing board, in terms of trying to figure out what causes chronic diseases.



Prof Paul Ewald often talks about the human genome project's failure to uncover chronic disease etiology. He has been trying to get people to understand that we need to be looking at other possible causal factors. In his view, it is germs, not genes, which are the likely main driving cause of chronic disease.

This makes sense, because most people were healthy before they caught their chronic disease. So something must have changed in their body to cause this disease. In science, every effect has a cause. The acquisition of a persistent pathogen in the body may well be that factor which turns a healthy body into a diseased one, says Ewald.

Prof Ewald argues that evolution is such a powerful force, than any disease-causing gene which reduces an animal's chances of reproduction would have been eliminated from the gene pool millions of years ago.

The only exceptions are bad genes which have some compensating positive benefit. He gives the example of sickle cell disease genes, which are common in Africa. These are bad genes which do lead to disease. But the same genes provide a very important compensating benefit: they protect against malaria, a common infection in Africa.

 

[SWAlexander]

Here is one example that could be a part of ME/CFS.
As far as I know, IL (Interleukin) plays a big part.

This chart shows all my genetic IL (Interleukin) and how they are connected to what possible illness.
(download and enlarge pic. for clear definition.) Not sure how good the screen print resolution shows up.

 

[SWAlexander]

30% is almost 1 in 3

I recall Dr Davis saying they didn't find any specific mutation that causes ME, though that tryptophan bit they are working on is found in 75%(?) of the population but only 1-2% get ME.

I did post about this in the ask Dr Davis thread but if @Janet Dafoe doesn't respond perhaps we need to contact Dr Miga ourselves?
Though i am not up to this, can anyone else take it on?

I tried many different ways to contact Dr. Davis without results. I tried to help to find details about ME/CFS.
I offered my med history, MRI, CT, and Pet scans, very extensive bloodwork and my DNA. The reason I did this is that I have a marker for “Muscle Composition” “Genetic result TT - genetic muscle composition is uncommon in elite power athletes.”

 

[Pyrrhus]

I also regularly hear in the periodic paralysis field, where ca. 30% of patients have no known mutation. 30% is pretty much.

This is purely anecdotal, but every ME patient I know who suffers from periodic paralysis (N=6) has no known mutation. Some of them have questioned whether their periodic paralysis is a symptom of ME.