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Exome Sequencing Identifies Potential Risk Variants for M endelian Disorders at High Prevalence in Q atar
Author(s) -
RodriguezFlores Juan L.,
Fakhro Khalid,
Hackett Neil R.,
Salit Jacqueline,
Fuller Jennifer,
AgostoPerez Francisco,
Gharbiah Maey,
Malek Joel A.,
Zirie Mahmoud,
Jayyousi Amin,
Badii Ramin,
AlNabet AlMarri Ajayeb,
Chouchane Lotfi,
Stadler Dora J.,
Mezey Jason G.,
Crystal Ronald G.
Publication year - 2014
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.22460
Subject(s) - mendelian inheritance , exome sequencing , biology , exome , genetics , penetrance , population , allele frequency , allele , 1000 genomes project , mutation , gene , single nucleotide polymorphism , genotype , medicine , phenotype , environmental health
Exome sequencing of families of related individuals has been highly successful in identifying genetic polymorphisms responsible for M endelian 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 M endelian diseases. We sequenced the exomes of 100 individuals representing the three major genetic subgroups of the Q atari population (Q1 Bedouin, Q2 Persian‐South Asian, Q3 African) and identified 37 variants in 33 genes with effects on 36 clinically significant M endelian diseases. These include variants not present in 1000 G enomes and variants at high frequency when compared with 1000 G enomes populations. Several of these M endelian variants were only segregating in one Q atari subpopulation, where the observed subpopulation specificity trends were confirmed in an independent population of 386 Q ataris. Premarital genetic screening in Q atar tests for only four out of the 37, such that this study provides a set of M endelian 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.