A small number of de novo assembled human genomes have been reported to date, and few have been complemented with population-based genetic variation, which is particularly important for North Africa, a region underrepresented in current genome-wide references. Here, we combine long- and short-read whole-genome sequencing data with recent assembly approaches into a de novo assembly of an Egyptian genome. The assembly demonstrates well-balanced quality metrics and is complemented with variant phasing via linked reads into haploblocks, which we associate with gene expression changes in blood. To construct an Egyptian genome reference, we identify genome-wide genetic variation within a 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 genome references. Thus, the Egyptian genome reference will be a valuable resource for precision medicine.

迄今为止，已经报道了少量从头组装的人类基因组，并且很少有基于人群的遗传变异得到补充，这对于北非尤为重要，因为该地区在当前全基因组参考文献中代表性不足。在这里，我们将长读长和短读长全基因组测序数据与最新的组装方法结合起来，对埃及基因组进行从头组装。该组装展示了良好平衡的质量指标，并通过链接读取到单倍体中补充了变体定相，我们将其与血液中的基因表达变化相关联。为了构建埃及基因组参考，我们在 110 名埃及人的队列中鉴定了全基因组遗传变异。我们表明，埃及人和欧洲人之间等位基因频率和连锁不平衡的差异可能会损害基于欧洲血统的遗传病风险和多基因评分的可转移性，证实了多种族基因组参考的需要。因此，埃及基因组参考将成为精准医学的宝贵资源。