New Genome Map Tries To Capture All Human Genetic Variation (technologyreview.com) 13
An anonymous reader shares an excerpt from MIT Technology Review: Today, researchers announced yet another version of the human genome map, which they say combines the complete DNA of 47 diverse individuals -- Africans, Native Americans, and Asians, among other groups -- into one giant genetic atlas that they say better captures the surprising genetic diversity of our species. The new map, called a "pangenome," has been a decade in the making, and researchers say it will only get bigger, creating an expanding view of the genome as they add DNA from another 300 people from around the globe. It was published in the journal Nature today. People's genomes are largely alike, but it's the hundreds of thousands of differences, often just single DNA letters, that explain why each of us is unique. The new pangenome, researchers say, should make it possible to observe this diversity in more detail than ever before, highlighting so-called evolutionary hot spots as well as thousands of surprisingly large differences, like deleted, inverted, or duplicated genes, that aren't observable in conventional studies. The pangenome relies on a mathematical concept called a graph, which you can imagine as a massive version of connect-the-dots. Each dot is a segment of DNA. To draw a particular person's genome, you start connecting the numbered dots. Each person's DNA can take a slightly different path, skipping some numbers and adding others.
One payoff of the new pangenome could be better ways to diagnose rare diseases, although practical applications aren't easy to name. Instead, scientists say it's mainly giving them insight into some of the "dark matter" of the genome that's previously been hard to see, including strange regions of chromosomes that seem to share and exchange genes. For now, most biologists and doctors will stick to the existing "reference genome," the one first produced in draft form in 2001 and gradually improved. It answers most questions researchers are interested in, and all their computer tools work with it. The reason a reference genome is important is that when a new person's genome is sequenced, that sequence is projected onto the reference in order to organize and read the new data. Yet since the current reference is just one possible genome, missing bits that some people have, some information can't be analyzed and is usually ignored. Researchers call this effect "reference bias" or, more simply, the streetlamp problem. You don't see where you don't look.
Officials with NIH said they hoped the new update to the genome map would make gene research more "equitable." That's because the more different your genome is from the current reference, the more information about you could be missed. The existing reference is largely the DNA of one African-American man, although it includes segments from several other people as well. "If the genome you want to analyze has sequences that are not in that reference, they will be missed in the analysis," says Deanna Church, a consultant with the business incubator General Inception, who previously held a key role at NIH managing the reference genome. "In reality, the notion that there is a 'human genome' is really the problem," she says. "The current version is the simplest model you can make. It made sense when we started ... But now we need better models."
One payoff of the new pangenome could be better ways to diagnose rare diseases, although practical applications aren't easy to name. Instead, scientists say it's mainly giving them insight into some of the "dark matter" of the genome that's previously been hard to see, including strange regions of chromosomes that seem to share and exchange genes. For now, most biologists and doctors will stick to the existing "reference genome," the one first produced in draft form in 2001 and gradually improved. It answers most questions researchers are interested in, and all their computer tools work with it. The reason a reference genome is important is that when a new person's genome is sequenced, that sequence is projected onto the reference in order to organize and read the new data. Yet since the current reference is just one possible genome, missing bits that some people have, some information can't be analyzed and is usually ignored. Researchers call this effect "reference bias" or, more simply, the streetlamp problem. You don't see where you don't look.
Officials with NIH said they hoped the new update to the genome map would make gene research more "equitable." That's because the more different your genome is from the current reference, the more information about you could be missed. The existing reference is largely the DNA of one African-American man, although it includes segments from several other people as well. "If the genome you want to analyze has sequences that are not in that reference, they will be missed in the analysis," says Deanna Church, a consultant with the business incubator General Inception, who previously held a key role at NIH managing the reference genome. "In reality, the notion that there is a 'human genome' is really the problem," she says. "The current version is the simplest model you can make. It made sense when we started ... But now we need better models."
A better idea. (Score:3, Interesting)
First off, the ONLY reason a reference human genome is even needed is because sequencing technology sucks. if Illumina's reads weren't short, we won't even need a reference genome. That's why I really prefer to use ONT even though their cost and error characteristics are annoying for now. We need that tech developed. Anyway, do we really need to combine individuals to make a "reference" human genome that nobody has? What we need to do instead is to select random mediocre idiot humans (I suppose Craig Venter does qualify) and sequence their genomes (preferably males). The important thing is that we need to characterize all of those volunteer's phenotypes and features. Does he get alzheimers. Is he diabetic? What's his IQ? Does he wear glasses. Out of that pool we should use the most characterized person as the reference. What happens now is that people look at a gene and assume it's normal without even checking Clinvar because it matches the reference.
Re: (Score:1, Troll)
They are all clearly inferior to Mr. 95548 who could do a much better job from his secret lab in his Mother's
Re: (Score:3)
Well, considering the the first genome to be sequenced was that of Craig Venter I'm not sure just what criteria were used to select samples. I don't think you can make any reasonable assumptions. They *could* have been carefully selected to be different, or they could have been "folks that were easy to get sample from".
I didn't check the article to see how many capoid samples they had, or Ainu, or.... There are lots of remote groups that are likely to have a few genes that differ from those of most other
Re:A better idea. (Score:4, Interesting)
"Do you honestly think that the people chosen for the current study weren't vetted within an inch of their lives, and picked using the most sophisticated sampling techniques available? "
Yes I honestly think that, because most of the samples are from the 1000 genomes project which is anonymous and only cares about the geographic/ancestral background of the individuals. If you don't believe me try to find out any health information about those individuals.
Graph (Score:2)
Re: (Score:3)
I found this article that explains it a little better than "connect the dots". https://www.statnews.com/2016/... [statnews.com]
Chuck Norris updates his DNA every 5 minutes (Score:3)
So good luck trying to index it all.
diverse individuals? (Score:2)
How can an individual be diverse? I think they are trying to says "diverse group".
Wokeness is really messing with our language.
Re: (Score:2)
FWIW, every person is has a diverse genetic code. The copying isn't without errors. That's one reason the gene-line cells reproduce so rarely. (And I'd bet without checking that most of the mutations originate in the male line. Because of copying errors.)
Re: (Score:2)
>How can an individual be diverse?
It's how straight white people in HR, marketing, and PR now refer to non-white or LGBT individuals.
Wait a decade, it'll have become offensive and something new will have replaced it.
Humans Surprisingly Genetically Homogeneous (Score:4, Interesting)
...the surprising genetic diversity of our species
Humans are surprisingly homogeneous [wikipedia.org] when it comes to genetics. It is thought that this is due to Toba catastrophe [wikipedia.org] that is thought to have reduced the human population to 1-10,000 breeding pairs. Other species typically show far more genetic variation than humans.
"all" variation? (Score:2)
While it's certainly a good idea to broaden the genome map from a single reference model to 'here's a centroid of that model, with +/- variations" it's pretty damn audacious - if not to say arrogant and practically impossible - to say we have "all".
Certainly there's a pareto point where there's a cloud of variations that LIKELY covers maybe 80% of the statistically-predicted potentially survivable variation. That map will be fascinating and interesting and useful.
But no damn way it will be anywhere close t
Slashdot readers could ... (Score:2)