title: Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar.
abstract: 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.
authors.affiliation: Department of Genetic Medicine, Weill Cornell Medical College, New York, New York.
authors.forename: Juan L
authors.initials: JL
authors.lastname: Rodriguez-Flores
authors.forename: Khalid
authors.initials: K
authors.lastname: Fakhro
authors.forename: Neil R
authors.initials: NR
authors.lastname: Hackett
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Salit
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fuller
authors.forename: Francisco
authors.initials: F
authors.lastname: Agosto-Perez
authors.forename: Maey
authors.initials: M
authors.lastname: Gharbiah
authors.forename: Joel A
authors.initials: JA
authors.lastname: Malek
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Zirie
authors.forename: Amin
authors.initials: A
authors.lastname: Jayyousi
authors.forename: Ramin
authors.initials: R
authors.lastname: Badii
authors.forename: Ajayeb
authors.initials: A
authors.lastname: Al-Nabet Al-Marri
authors.forename: Lotfi
authors.initials: L
authors.lastname: Chouchane
authors.forename: Dora J
authors.initials: DJ
authors.lastname: Stadler
authors.forename: Jason G
authors.initials: JG
authors.lastname: Mezey
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
mesh_terms: D002877:Chromosomes, Human / Q000235:genetics*; D030541:Databases, Genetic; D059472:Exome; D005260:Female; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000453:epidemiology / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D014644:Genetic Variation; D006801:Humans; D008297:Male; D015995:Prevalence; D011780:Qatar / Q000453:epidemiology; D017422:Sequence Analysis, DNA
keywords: Mendelian; OMIM; consanguinity; diagnostic biomarkers; exome sequencing