A draft Arab pangenome reference

Abstract Human pangenomes provide a comprehensive portrayal of genetic diversity of humans, yet it lacks representation of Arab populations. We constructed the Arab Pangenome Reference (APR) from 43 individuals with diverse Arab ethnicities. Nuclear and mitochondrial pangenomes were constructed utilizing 35.52X High fidelity long reads and 53.54X ultra-long reads. This yielded high-quality contiguous (average N50=106.81 Mb) de novo assemblies that used over 99% of the sequences constructing haplotype phased diploid genome assemblies with 88% exhibited larger genome length (average 3.01 gigabase) than the prevailing human reference GRCh38. We discovered 100.93 million base pairs of novel euchromatic sequences that were not present in recent human pangenomes and in the human genome references (T2T-CHM13 and GRCh38). We identified 10.68 million population-specific small variants, 108,709 structural variants, and 838 genes (13.24% recessive disease genes) duplication from the Arab pangenome. On exploring the mitochondria pangenome, we uncovered 718 bp of novel sequences. Our study provides a valuable resource for future genetic research and genomic medicine initiatives in the Arab populations and other populations with similar genetic backgrounds.