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

Publication Type	Academic Article
Authors	Rodriguez-Flores J, Fakhro K, Hackett N, Salit J, Fuller J, Agosto-Perez F, Gharbiah M, Malek J, Zirie M, Jayyousi A, Badii R, Al-Nabet Al-Marri A, Chouchane L, Stadler D, Mezey J, Crystal R
Journal	Hum Mutat
Volume	35
Issue	1
Pagination	105-16
Date Published	11/10/2013
ISSN	1098-1004
Keywords	Chromosomes, Human, Genetic Diseases, Inborn, Genetic Predisposition to Disease, Genetic Testing, Genetic Variation, Sequence Analysis, DNA
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.
DOI	10.1002/humu.22460
PubMed ID	24123366
PubMed Central ID	PMC3908915