سجل مستودعي · ncbi-prjeb5139

A systematic analysis of two whole genomes and thirteen exomes from Saudi Arabian tribes

The Kuwaiti population is composed of three genetic subgroups of Persian, Saudi Arabian tribe and Bedouin origin. The Saudi Arabian tribe subgroup traces its origin to the Najd region of Saudi Arabia. By sequencing two whole genomes and thirteen exomes from this subgroup at high coverage (>40X), we identify 4,950,724 Single Nucleotide Polymorphisms (SNPs), 515,802 indels and 39,762 structural variations. Of the total identified variants, 10,098 (8.3%) exomic SNPs, 139,923 (2.9%) non-exomic SNPs, 5,256 (54.3%) exomic indels, and 374,959 (74.08%) non-exomic indels are ‘novel’. Up to 8,070 (79.9%) novel biallelic exomic SNPs are seen in low frequency (minor allele frequency < 5%). We observe 5,462 known and 1,004 novel potentially deleterious nonsynonymous SNPs. Allele Frequencies of common SNPs derived using the 15 exomes is significantly correlated with those derived using genotype data from a larger cohort of 48 individuals (Pearson correlation coefficient, 0.91; p <2.2x10-16). A set of 2,485 SNPs show significantly different allele frequencies as compared to populations from other continents. Two notable variants having risk alleles seen in high frequencies in the Saudi Arabian tribe subgroup are: a nonsynonymous deleterious SNP (rs2108622, CYP4F2 gene) associated with warfarin dosage levels required to elicit normal anticoagulant response; and a 3’UTR SNP (rs6151429, ARSA gene) associated with Metachromatic Leukodystrophy. Hemoglobin Riyadh variant (identified for the first time in a Saudi Arabian woman) is observed in the presented exome data. The profile of the mitochondrial haplogroups derived from the 15 individuals is consistent with the haplogroup diversity seen in Saudi Arabian natives, who are believed to have received substantial gene flow from Africa and eastern provenance. We present the first genome resource for designing genetic studies in Saudi Arabian tribe subgroup.