Human Pangenomics: Promises and Challenges of a Distributed Genomic Reference

Abstract

A pangenome is a collection of the common and unique genomes that are present in a given species. It combines the genetic information of all the genomes sampled, resulting in a large and diverse range of genetic material. Pangenomic analysis offers several advantages compared to traditional genomic research. For example, a pangenome is not bound by the physical constraints of a single genome, so it can capture more genetic variability. Thanks to the introduction of the concept of pangenome, it is possible to use exceedingly detailed sequence data to study the evolutionary history of two different species, or how populations within a species differ genetically. In the wake of the Human Pangenome Project, this review aims at discussing the advantages of the pangenome around human genetic variation, which are then framed around how pangenomic data can inform population genetics, phylogenetics, and public health policy by providing insights into the genetic basis of diseases or determining personalized treatments, targeting the specific genetic profile of an individual. Moreover, technical limitations, ethical concerns, and legal considerations are discussed.

Keywords: bioinformatics; evolution; human genomics; pangenome; pangenomics; personalized medicine; phylogenetics; public health; selection; structural variation.

Figure 1

Example of core and accessory genome from three sequenced samples.

Figure 2

Example of a comparative and a graph interpretation of the pangenome based on three sequenced individuals. Symbols correspond to genomic elements belonging to the core, shell or cloud genome as shown in Figure 1. Colors represent elements in the same position. Individual 1 (Ind1) shows a duplication of the third genomic element, which is different than the one carried by the other individuals and is, therefore, part of the cloud genome.