Exome Sequencing of Only Seven Qataris Identifies Potentially Deleterious Variants in the Qatari Population

Rodríguez-Flores, Juan L.; Fuller, Jennifer; Hackett, Neil R.; Salit, Jacqueline; Malek, Joel A.; Al-Dous, Eman K.; Chouchane, Lotfi; Zirie, Mahmoud; Jayoussi, Amin; Mahmoud, Mai; Crystal, Ronald G.; Mezey, Jason G.

doi:10.1371/journal.pone.0047614

Cited by 16 publications

(28 citation statements)

References 37 publications

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“…Although there have been many analyses of Chr Y and mtDNA sampled from Arab individuals (Abu-Amero et al 2007Rowold et al 2007), and there have been previous surveys of genetic variation of people within the peninsula and immediately surrounding regions conducted with genotyping arrays (Behar et al 2010;HunterZinck et al 2010;Alsmadi et al 2013;Markus et al 2014;Shriner et al 2014) and deep exome sequencing (Rodriguez-Flores et al 2012, 2014Alsmadi et al 2014), and by individual high-coverage genomes (Alsmadi et al 2014;John et al 2015), the sample of rare and common genetic variation throughout the genome in our sample provides a far more complete picture of how both ancient and recent migration events have contributed to the genetics of the modern peoples of the Arabian Peninsula. For understanding how human migration history has determined the structure of modern genomes, our identification of a cluster of Q1 (Bedouin) as the most distant ancestors of non-Africans is of considerable interest, particularly given the suspected route of migration out of Africa and into the surrounding continents.…”

Section: Uninterrupted Ancestry In Arabiamentioning

confidence: 99%

“…Natives of the Arabian Peninsula can be divided into at least three genetic subpopulations that reflect the historical migration patterns in the region: Q1 (Bedouin), Q2 (Persian-South Asian), and Q3 (African) (Hunter-Zinck et al 2010;Omberg et al 2012;Rodriguez-Flores et al 2012). A panel of 48 SNPs was genotyped by TaqMan (Life Technologies) sufficient for classification into one of the three subpopulations based on >70% ancestry in one cluster in a STRUCTURE analysis with k = 3 used to identify individuals that could unambiguously be placed in one of these three groups (Supplemental Fig.…”

Section: Inclusion Criteriamentioning

confidence: 99%

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Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

et al. 2016

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An open question in the history of human migration is the identity of the earliest Eurasian populations that have left contemporary descendants. The Arabian Peninsula was the initial site of the out-of-Africa migrations that occurred between 125,000 and 60,000 yr ago, leading to the hypothesis that the first Eurasian populations were established on the Peninsula and that contemporary indigenous Arabs are direct descendants of these ancient peoples. To assess this hypothesis, we sequenced the entire genomes of 104 unrelated natives of the Arabian Peninsula at high coverage, including 56 of indigenous Arab ancestry. The indigenous Arab genomes defined a cluster distinct from other ancestral groups, and these genomes showed clear hallmarks of an ancient out-of-Africa bottleneck. Similar to other Middle Eastern populations, the indigenous Arabs had higher levels of Neanderthal admixture compared to Africans but had lower levels than Europeans and Asians. These levels of Neanderthal admixture are consistent with an early divergence of Arab ancestors after the out-of-Africa bottleneck but before the major Neanderthal admixture events in Europe and other regions of Eurasia. When compared to worldwide populations sampled in the 1000 Genomes Project, although the indigenous Arabs had a signal of admixture with Europeans, they clustered in a basal, outgroup position to all 1000 Genomes non-Africans when considering pairwise similarity across the entire genome. These results place indigenous Arabs as the most distant relatives of all other contemporary non-Africans and identify these people as direct descendants of the first Eurasian populations established by the out-of-Africa migrations.

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Section: Uninterrupted Ancestry In Arabiamentioning

confidence: 99%

Section: Inclusion Criteriamentioning

confidence: 99%

Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

et al. 2016

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“…The aim of this study is to analyse a series of inbred Qatari families, mainly belonging to the genetic cluster consistent with Arabian origin or Bedouin [6] , by using the homozygosity mapping process to identify genomic regions that potentially harbour an excess of deleterious mutations. Previous studies [7,8] have demonstrated that in Qatari samples, many predicted deleterious SNPs occur at significantly high frequencies, providing useful information for the epidemiological profile of this population. Moreover, the Qatari population has recently evolved from three tribes from Persia, the Arabian Peninsula, and Oman.…”

Section: Introductionmentioning

confidence: 99%

Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

et al. 2015

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Objective: The aim of this study is to evaluate the fraction of putatively deleterious variants within genomic runs of homozygosity (ROH) regions in an inbred and selected cohort of Qatari individuals. Methods: High-density SNP array analysis was performed in 36 individuals, and for 14 of them whole-exome sequencing (WES) was also carried out. Results: In all individuals, regions characterized by a high (hotspot) or low (coldspot) degree of homozygosity in all the analysed individuals were mapped, and the most frequent hotspot regions were selected. WES data were exploited to identify the single nucleotide variations (SNVs) harboured by genes located within both regions in each individual. Evolutionary conservation-based algorithms were employed to predict the potential deleteriousness of SNVs. The amount of in silico predicted deleterious SNVs was significantly different (p < 0.05) between homozygosity hotspot and coldspot regions. Conclusion: Genes located within ROH hotspot regions contain a significant burden of predicted putatively deleterious variants compared to genes located outside these regions, suggesting inbreeding as a possible mechanism allowing an enrichment of putatively deleterious variants at the homozygous state.

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“…Despite the importance of the Qatari people in the history of human evolution and the importance of this nation in the region and globally, there have been relatively few applications of genome‐wide microarray genotyping [Hunter‐Zinck et al., ; Omberg et al., ] or high‐throughput next‐generation sequencing to study this population [Rodriguez‐Flores et al., ], particularly in comparison with populations that have been sampled as part of major genomics consortiums such as the Human Genome Diversity Project (HGDP) [Cann et al., ], HapMap [Altshuler et al, ], or the 1000 Genomes (1000G) Project [1000 Genomes Project Consortium, ]. As a consequence, there is limited information concerning the genomes of the Qatari people.…”

Section: Introductionmentioning

confidence: 99%

Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

et al. 2013

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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 to 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. Pre-marital genetic screening in Qatar tests for only 4 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.

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Exome Sequencing of Only Seven Qataris Identifies Potentially Deleterious Variants in the Qatari Population

Cited by 16 publications

References 37 publications

Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

Indigenous Arabs are descendants of the earliest split from ancient Eurasian populations

Increased Rate of Deleterious Variants in Long Runs of Homozygosity of an Inbred Population from Qatar

Exome Sequencing Identifies Potential Risk Variants for Mendelian Disorders at High Prevalence in Qatar

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