“From complete genomes to pangenomes:  Expanding our understanding of human haplotype variation”

Abstract

The initial Human Genome Project was a landmark achievement, serving as an essential resource for basic and clinical science, as well as for understanding human history, for over two decades. However, it needs an upgrade due to missing data, inaccurately assembled regions, and its inability to fully represent and identify sequence variants equitably. A single reference map, regardless of its completeness, cannot encapsulate the variation across the human population, leading to biases and ultimately inequity in genomic studies. Recognizing this limitation, the new initiative known as the Human Pangenome Project aims to deliver hundreds of highly accurate and complete genomes. This effort intends to define all bases of each chromosome from telomere to telomere (T2T), ensuring a broader representation of common variants across the human species. Achieving these goals will require the rise of new tools and technology standards for complete genome assemblies and pangenomics, which will have broad and lasting impact on genomic research.