A personal and population-based Egyptian genome reference

The human genome is composed of 23 chromosomal DNA sequences of bases A, C, G and T -- the blueprint to implement the molecular functions that are at the basis of every individual. Deciphering the first human genome was a consortium effort that took more than a decade and cost about 3 billion dollars. With latest technological advances, determining an individuals entire personal genome at manageable cost and effort comes into reach. Although the benefit of all-encompassing genetic information that entire genomes provide is widely noted, so far only a small number of de novo assembled human genomes have been reported. Even less have been characterized and complemented with respect to population-specific variation. Here we combine long- and short-read whole genome next-generation sequencing data together with the recent assembly approaches for the first de novo assembly of the genome of an Egyptian individual, which we merged with Egyptian variant data into a population reference genome. The resulting genome assembly demonstrates overall well-balanced quality metrics and comes along with high quality variant phasing into maternal and paternal haplotypes. Further, we assayed population-specific variations genome-wide within a representative cohort of more than 100 Egyptian individuals. By annotation of these genetic data and integration with public databases we showcase genetic variants that alter protein sequence and that are linked to allelic gene expression. This is one of a handful of studies that comprehensively describe a population reference genome based on a high-quality personal genome and which highlights population-specific variants of interest. It is a proof-of-concept to be considered by the many national genome initiatives underway. And, more importantly, we anticipate that the Egyptian reference genome will be a valuable resource for precision medicine initiatives targeting the Egyptian population and beyond.