An integrated personal and population-based Egyptian genome reference

Abstract

The human genome is composed of chromosomal DNA sequences consisting of bases A, C, G and T – the blueprint to implement the molecular functions that are the basis of every individual’s life. Deciphering the first human genome was a consortium effort that took more than a decade and considerable cost. With the latest technological advances, determining an individual’s entire personal genome with manageable cost and effort has come within reach. Although the benefits of the all-encompassing genetic information that entire genomes provide are manifold, only a small number of de novo assembled human genomes have been reported to date ^1–3, and few have been complemented with population-based genetic variation ⁴, which is particularly important for North Africans who are not represented in current genome-wide data sets ^5–7. Here, we combine long- and short-read whole-genome next-generation sequencing data with recent assembly approaches into the first de novo assembly of the genome of an Egyptian individual. The resulting assembly demonstrates well-balanced quality metrics and is complemented with high-quality variant phasing via linked reads into haploblocks, which we can associate with gene expression changes in blood. To construct an Egyptian genome reference, we further assayed genome-wide genetic variation occurring in the Egyptian population within a representative cohort of 110 Egyptian individuals. We show that differences in allele frequencies and linkage disequilibrium between Egyptians and Europeans may compromise the transferability of European ancestry-based genetic disease risk and polygenic scores, substantiating the need for multi-ethnic genetic studies and corresponding genome references. The Egyptian genome reference represents a comprehensive population data set based on a high-quality personal genome. It is a proof of concept to be considered by the many national and international genome initiatives underway. More importantly, we anticipate that the Egyptian genome reference will be a valuable resource for precision medicine targeting the Egyptian population and beyond.