The Quest for Humanity’s Genetic Blueprint

Thursday - May 18 2023, 17:59 UTC - 1 year ago

A new study published in Nature is taking the first step to broaden the scope of our understanding of the human genome through the Human Pangenome Reference Consortium (HPRC), capturing the genomes of 47 people from Asia, Africa, the Americas, and Europe. This pangenome is a library of genetic histories of people around the world and can help scientists hone in on genetic links for diseases that current reference genome might not be able to.

Think of the first draft of the human genome as a book. Published just past the turn of the century, the human genome paved the way for transformative therapeutics. Gene editing and gene therapies now battle previously untreatable diseases. Comparing the A, T, C, and G genetic letters with those of our closest evolutionary cousins is unveiling the roots of our evolution and intelligence.

But what, or who, does "our" refer to? .

Due to technological constraints, the current reference genome was assembled from chunks of sequenced DNA from a handful of people, mostly of European and African descent. Although invaluable for hunting down genetic diseases, the "book of humanity" hardly encapsulates the genetic diversity of people around the globe.

A new study published in Nature is taking the first step to broaden its scope. Roughly a decade in the making, the study captured the genomes of 47 people from Asia, Africa, the Americas, and Europe. The herculean effort sequenced a total of 94 genomes, one for each set of chromosomes for each person.

The end result is the first draft of the human "pangenome"—a collection of genetic data from each individual carefully compiled into a single reference. Rather than a book, the new data structure is now a library, capturing the rich genetic history of humans around the world.

"This is like going from black-and-white television to 1080p," said Dr. Keolu Fox at the University of California, San Diego, who was not involved in the study.

The study is part of the Human Pangenome Reference Consortium (HPRC), an ambitious international project launched in 2019 to capture the diversity of our species into a comprehensive reference dictionary. Far from an academic pursuit, a diverse reference helps scientists hone in on genetic links for diseases, regardless of ancestry.

"It’s an exceptional advance… It’s making the picture of human genetic variation more accurate and more complete," said Dr. Mashaal Sohail at the National Autonomous University of Mexico, who was not involved in the study.

--- The Quest for Humanity’s Genetic Blueprint --- .

The first draft of the human genome was a triumph. But with eight percent of details missing, it also contained bias.

In genetic studies, scientists often match up patients’ genomes to the reference genome to hunt down disease-causing DNA variants. But similar to checking typos using a dictionary, the process suffers if the dictionary is incomplete, or if it only contains one version of a word’s spelling (American "humor" versus British "humour," for example).

Without a full diverse DNA atlas, it’s difficult to decipher genes linked to rare diseases—especially when multiple genes are involved, or if the answers are buried inside complex DNA structures unique to a certain population.

Then there’s the problem of diagnosis and therapeutics. Cancer predictors, for example, may not work as well for those of Asian and African heritage, because they were developed using a largely European genomic reference.

Well aware of these hiccups, scientists have been adding to the first draft for decades, with the most recent update GRCh38 released in 2017. Although containing DNA from 20 people, the database is dominated by one person with over 70 percent contribution. Last year, another group released a map that tried to even the contribution of each person.