The Human Genome Project: A Decade in the Making

Thursday - May 11 2023, 15:22 UTC - 1 year ago

The Human Genome Project has been announced as "finished" multiple times, but today's announcement of a "pangenome" map of 47 people's genomes is said to better capture the genetic diversity of our species and will only get bigger. The new Pangenome will allow for better understanding of rare diseases and previously unseen "dark matter" of the genome.

The joke about the Human Genome Project is how many times it’s been finished, but not actually.

The first time was in 2000,when Bill Clinton announced the "first survey of the entire human genome" at a White House ceremony, calling it "the most important and most wondrous map ever produced by humankind." .

But the job wasn’t done. A year later, the triumph was announced again, this time with the formal publication of a "draft" of "the genetic blueprint for a human being." .

In 2003, researchers had another go at the finish line, claiming the "successful completion" of the project, citing better levels of accuracy. Nineteen years later, in 2022, they again claimed victory, this time for a really, truly "complete" sequence of one genome—end to end, no gaps at all. Pinkie promise.

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.

"We now understand that having one map of a single human genome cannot adequately represent all of humanity," says Karen Miga, a professor at the University of California, Santa Cruz, and a participant in the new project.

--- Diversity in detail --- .

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 analyzable.