DALIA- a comprehensive resource of Disease Alleles in Arab population

Abstract

The Arab population encompasses over 420 million people characterized by genetic admixture and a consequent rich genetic diversity. A number of genetic diseases have been reported for the first time from the population. Additionally a high prevalence of some genetic diseases including autosomal recessive disorders such as hemoglobinopathies and familial mediterranean fever have been found in the population and across the region. There is a paucity of databases cataloguing genetic variants of clinical relevance from the population. The availability of such a catalog could have implications in precise diagnosis, genetic epidemiology and prevention of disease. To fill in the gap, we have compiled DALIA, a comprehensive compendium of genetic variants reported in literature and implicated in genetic diseases reported from the Arab population. The database aims to act as an effective resource for population-scale and sub-population specific variant analyses, enabling a ready reference aiding clinical interpretation of genetic variants, genetic epidemiology, as well as facilitating rapid screening and a quick reference for evaluating evidence on genetic diseases.

Fig 1. The DALIA homepage.

It provides an easy to use interface for searching and retrieving the compiled information on genetic variants. The ‘Example Search’ section illustrates numerous query formats in which the database can be explored.

Fig 2. Expanded search results.

Each selected search result links to a page containing complete information about the variant, including information about the gene, disease, genome level information as well as allele frequencies and various predictive scores that could help establish pathogenicity. Further, links to various other resources including Pubmed, Clinvar, dbSNP and OMIM are also included for a more complete picture of the variant.

Fig 3. Comparison of allele frequencies.

The figure represents a subset (p-value < 0.01) of all statistically significant variants obtained after applying the Fisher’s Exact Test (S1 Fig). The orange circles highlight variants that were significantly different either within the Qatar or GME subpopulations, or with respect to global population averages ExAC and 1000 Genomes. The populations shown are, in order: Qatari population (QALL) and sub-populations African (AFR), Arab (QARB), Bedouin (QBED), Persian (QPER), and South Asian (QSAS), GME population (GME-ALL), and sub-populations northwest Africa (GME-NWA), northeast Africa (GME-NEA), Arabian peninsula (GME-AP), Israel (GME-Israel), Syrian desert (GME-SD), Turkish peninsula (GME-TP) and Central Asia (GME-CA), ExAC population (EXAC-ALL), sub-populations African/African American (EXAC-AFR), Latino (EXAC-AMR), East Asian (EXAC-EAS), Finnish (EXAC-FIN), Non-Finnish European (EXAC-NFE), South Asian (EXAC-SAS) and Other (EXAC-OTH), 1000 Genomes population(1KG-ALL) and sub-populations African(1KG-AFR), Ad Mixed American(1KG-AMR), East Asian(1KG-EAS), European(1KG-EUR) and South Asian(1KG-SAS).

Fig 4. Signatures of positive selection in the ATP7B gene in the Qatar population.

The figure depicts the iHS scores (top) for all known variants of the ATP7B gene plotted along the length of the gene loci shown below. The subsequent boxes depict all the pairwise Fst scores for the Qatar population as a whole (QALL), as well as all its subpopulations (QAFR, QARAB, QBED, QPER, and QSAS). The array of lines at the bottom represents all known variants along the length of the gene, the exon structure of which is shown beneath it.

Fig 5. Allele frequency heat map.

The figure depicts the variation in allele frequency distribution of all known G6PD pathogenic/likely pathogenic variants across four major datasets—Qatar, GME, 1000 Genomes and ExAC.