The Qatar genome: a population-specific tool for precision medicine in the Middle East

Abstract

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population. A total of 20.9 million single nucleotide polymorphisms (SNPs) and 3.1 million indels were observed in Qatar, including an average of 1.79% novel variants per individual genome. Replacement of the GRCh37 standard reference with QTRG in a best practices genome analysis workflow resulted in an average of 7* deeper coverage depth (an improvement of 23%) and 756,671 fewer variants on average, a reduction of 16% that is attributed to common Qatari alleles being present in QTRG. The benefit for using QTRG varies across ancestries, a factor that should be taken into consideration when selecting an appropriate reference for analysis.

Figure 1

Differences in mapped read depth across reference genomes. In order to select the optimal reference for analysis of Qatari genomes and exomes, the mapped read depth was compared between GRCh37 and three alternative reference genomes based on MAAs observed in n=1005 Qatari. Illumina paired-end 100 bp reads for 37* genome sequencing of a female Qatari were mapped using BWA to GRCh37, QTRG1, QTRG2 and QTRG3 reference genomes. The differences between the three Qatari references is that QTRG1 incorporates MAA SNPs, QTRG2 incorporates MAA indels, and QTRG3 incorporates both MAA SNPs and MAA indels. The depth of coverage was measured at (a) across the genome and (b) at MAA sites modified in the QTRG. MAAs, major alternate alleles; SNP, single nucleotide polymorphism.