Background Consanguinity and endogamy are common in the Middle East, resulting in a higher frequency of autosomal recessive (AR) disorders. This consanguinity facilitates discovery of disease causative genes particularly after introduction of the new techniques such as Whole Exome Sequencing (WES). In order to reduce the overall socio-economic burden of such diseases, the development of diagnostic tools and prevention strategies must be a priority. To achieve these goals, the causal genes underlying human genetic diseases should be first discovered. The goal of this study is to identify novel genes causing AR diseases in Qatari population using WES. Methods Genomic DNAs were captured with the Illumina TruSeq library and sequenced with Illumina HiSeq2000. The reads were aligned to the reference genome using BWA. Variants calling and annotation were performed by SAMtools and ANNOVAR, respectively. Novel variants were defined as those having an allele frequency <0.05 in the 1000 Genomes database and predicted to be nonsynonymous substitutions. Results WES was applied on affected individuals of 3 consanguineous families with Mental Retardation (MR: 2 siblings), Peripheral Neuropathy (PN: 2 siblings) and Eye Anomaly (EA: 1 male). The mode of inheritance was assumed to be AR in MR and PN families. This led to identification of 3 and 4 homozygous candidate variants, shared by two siblings, respectively. The mode of inheritance in EA was considered to be AR and/or X-linked that led to the identification of 26 autosomal homozygous and 6 X-linked genes. The function of one of the genes on X-chromosome was related to the patient phenotype. Conclusions These preliminary interesting results highlight the power of WES, to identify potential candidate genes for AR disorders. The identified genes will be considered for functional follow-up investigation and further characterization. However, our results also highlight that the large number of population-specific variants - which may be common polymorphisms in Qatar but are so far absent from public databases - make diagnosis and discovery more difficult than in well-studied Caucasian populations. We urge genetics researchers in Qatar to actively participate in the creation of a local variant database, which will greatly facilitate such future studies.


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