Most comprehensive map of genomic variants in an Arab population

A new analysis offers the most comprehensive map of large scale genomic variants in the Qatari population.

Global genomic databases provide an insight into genetic differences in populations, but have so far been mostly based on data from individuals of European ancestry; people of Arab ancestry are significantly underrepresented (see BioNews 1293 and 1318). Researchers from King's College London and Sidra Medicine, Qatar, analysed over 6000 Qatari genomes across five major sub-population groups to create the most comprehensive map of large-scale genetic structural variants (SVs) in the Qatari population. The study offers an insight into genetic diversity among Arab populations.

'Structural variants have an important impact on human biology, but they've been largely understudied... We've created the most detailed map of these variants in the Arab population,' said Dr Mario Falchi from King's College London, co-senior author of the study published in Nature Communications. 'This gives us a much clearer view of genetic diversity in the region and paves the way for precision medicine.'

SVs include deletions, duplications or rearrangements of DNA fragments, rather than single-nucleotide variants, which had been the focus of previous Qatari genome studies (see BioNews 1088). The study identified more than 150,000 SVs, including over 12,000 affecting protein-coding genes. Many of the unveiled changes are associated with conditions prevalent in the regional context, such as cardiovascular disease and diabetes. This was demonstrated in the study by linking the genetic data with health metrics from Qatar Biobank, which includes detailed health information from more than 40,000 Qataris.

The high rate of consanguineous marriage in the Qatari population allowed the researchers to examine the health effects of homozygous deletions (inherited from both parents) in protein-coding genes, and reveal essential genomic regions that cannot be lost without compromising survival.

The researchers identified more than 180 deleted, or 'knocked-out', genes, which resulted in loss of specific proteins. Among these genes was CD36, resulting in a lack of the CD36 protein in the bloodstream and altered related blood markers. These findings, relevant to any population, offer rare insights into gene function, yet are difficult to study outside of the consanguineous context.

'Not only have we unveiled the most comprehensive map to date of structural variants from an Arab population, but we have also leveraged extensive biobank traits to link these to health and diseases,' said Professor Khalid Fakhro, chief research officer at Sidra Medicine and lead principal investigator of the study. 'We look forward to expanding these studies to tens of thousands of Qatari genomes in the next phase, and to contribute to global efforts in genetic mapping and population-scale health discovery.'