Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar.

Publication TypeJournal Article
Year of Publication2014
AuthorsRodriguez-Flores JL, Fakhro K, Hackett NR, Salit J, Fuller J, Agosto-Perez F, Gharbiah M, Malek JA, Zirie M, Jayyousi A, Badii R, Al-Marri AAl-Nabet, Chouchane L, Stadler DJ, Mezey JG, Crystal RG
JournalHum Mutat
Date Published2014 Jan
KeywordsChromosomes, Human, Databases, Genetic, Exome, Female, Gene Frequency, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genetic Testing, Genetic Variation, Humans, Male, Prevalence, Qatar, Sequence Analysis, DNA

Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for Mendelian disorders. Here, we demonstrate the value of the reverse approach, where we use exome sequencing of a sample of unrelated individuals to analyze allele frequencies of known causal mutations for Mendelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Qatari population (Q1 Bedouin, Q2 Persian-South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant Mendelian diseases. These include variants not present in 1000 Genomes and variants at high frequency when compared with 1000 Genomes populations. Several of these Mendelian variants were only segregating in one Qatari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Qataris. Premarital genetic screening in Qatar tests for only four out of the 37, such that this study provides a set of Mendelian disease variants with potential impact on the epidemiological profile of the population that could be incorporated into the testing program if further experimental and clinical characterization confirms high penetrance.

Alternate JournalHum. Mutat.
PubMed ID24123366
PubMed Central IDPMC3908915
Grant ListT32 HL094284 / HL / NHLBI NIH HHS / United States
T32 HL09428 / HL / NHLBI NIH HHS / United States