These authors contributed equally to this work.
Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar
Article first published online: 10 NOV 2013
© 2013 WILEY PERIODICALS, INC.
Volume 35, Issue 1, pages 105–116, January 2014
How to Cite
Rodriguez-Flores, J. L., Fakhro, K., Hackett, N. R., Salit, J., Fuller, J., Agosto-Perez, F., Gharbiah, M., Malek, J. A., Zirie, M., Jayyousi, A., Badii, R., Al-Nabet Al-Marri, A., Chouchane, L., Stadler, D. J., Mezey, J. G. and Crystal, R. G. (2014), Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar. Hum. Mutat., 35: 105–116. doi: 10.1002/humu.22460
Contract grant sponsors: Qatar Foundation and Weill Cornell Medical College – Qatar; National Science Foundation (#0922432); NIH T32 HL09428.
Communicated by David S. Rosenblatt
- Issue published online: 18 DEC 2013
- Article first published online: 10 NOV 2013
- Accepted manuscript online: 10 OCT 2013 11:56AM EST
- Manuscript Accepted: 25 SEP 2013
- Manuscript Received: 21 FEB 2013
- Qatar Foundation and Weill Cornell Medical College – Qatar
- National Science Foundation. Grant Numbers: #0922432, NIH T32 HL09428
- exome sequencing;
- diagnostic biomarkers
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.