Thousands of Qatari genomes inform human migration history and improve imputation of Arab haplotypes

Razali, Rozaimi Mohamad; Rodríguez-Flores, Juan L.; Ghorbani, Mohammadmersad; Naeem, Haroon; Aamer, Waleed; Aliyev, Elbay; Jubran, Ali Mohammad; Ismail, Said I.; Al‐Muftah, Wadha; Badji, Radja; Mbarek, Hamdi; Darwish, Dima; Fadl, Tasnim; Yasin, Heba; Ennaifar, Maryem; Abdellatif, Rania; Alkuwari, Fatima; Alvi, Muhammad Arshad; Al‐Sarraj, Yasser; Saad, Chadi; Althani, Asmaa; Fethnou, Eleni; Qafoud, Fatima; Alkhayat, Eiman; Afifi, Nahla; Tomei, Sara; Liu, Wei; Lorenz, Stephan; Syed, Najeeb; Almabrazi, Hakeem; Vempalli, Fazulur Rehaman; Temanni, Ramzi; Saqri, Tariq Abu; Khatib, Mohammedhusen; Hamza, Mehshad; Zaid, Tariq Abu; Khouly, Ahmed El; Pathare, Tushar; Poolat, Shafeeq; Al‐Ali, Rashid; Al‐Khodor, Souhaila; Al-Shafai, Mashael; Badii, Ramin; Chouchane, Lotfi; Estivill, Xavier; Puthen, Jithesh V.; Suhre, Karsten; Tatari, Zohreh; Clark, Andrew G.; Fakhro, Khalid; Mokrab, Younes

doi:10.1038/s41467-021-25287-y

Cited by 27 publications

(39 citation statements)

References 78 publications

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“…Similarly, the median number of singletons is lower for PAR cluster compared with other subclusters reflects the closely related individual present in this cluster (Table 2). Furthermore, runs of homozygosity (ROH) analysis of the QGP done by Razali et al (2021), identified per population ROH boundary for short, medium, and long ROH. We observed that Peninsular Arabs (PAR) have the lowest median for short ROH after African-based populations.…”

Section: Genetic Ancestry and Diversity Of The Qatari Populationmentioning

confidence: 99%

Qatar genome: Insights on genomics from the Middle East

et al. 2022

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Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is underrepresented in the human genome variation databases. Here we describe insights from Phase 1 of the Qatar Genome Program with whole genome sequenced 6047 individuals from Qatar. We identified more than 88 million variants of which 24 million are novel and 23 million are singletons. Consistent with the high consanguinity and founder effects in the region, we found that several rare deleterious variants were more common in the Qatari population while others seem to provide protection against diseases and have shaped the genetic architecture of adaptive phenotypes. These results highlight the value of our data as a resource to advance genetic studies in the Arab and neighboring Middle Eastern populations and will significantly boost the current efforts to improve our understanding of global patterns of human variations, human history, and genetic contributions to health and diseases in diverse populations.

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Section: Genetic Ancestry and Diversity Of The Qatari Populationmentioning

confidence: 99%

Qatar genome: Insights on genomics from the Middle East

et al. 2022

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“…More recently, a study sequencing whole genomes from 6218 Qatar individuals identified 74,783,226 variants, of which 28% were not present in current databases, mainly 1KG project, Human Origin dataset, and GME [20]. These studies and our analyses highlight the importance of expanding genomic sequencing studies among diverse underrepresented populations, which include variation that has not yet been sampled.…”

Section: Discussionmentioning

confidence: 67%

“…Similarly, Fattahi and his colleagues performed whole-exome sequencing on 800 individuals from eight major Iranian ethnic groups and identified 1,575,702 variants, of which 308,311 were novel (19.6%), compared to current databases, including gnomAD [ 19 ]. More recently, a study sequencing whole genomes from 6218 Qatar individuals identified 74,783,226 variants, of which 28% were not present in current databases, mainly 1KG project, Human Origin dataset, and GME [ 20 ]. These studies and our analyses highlight the importance of expanding genomic sequencing studies among diverse underrepresented populations, which include variation that has not yet been sampled.…”

Section: Discussionmentioning

confidence: 99%

Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome

Ramaswamy

Jain

Naofal

et al. 2022

JPM

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Genetic variation in populations of Middle Eastern origin remains highly underrepresented in most comprehensive genomic databases. This underrepresentation hampers the functional annotation of the human genome and challenges accurate clinical variant interpretation. To highlight the importance of capturing genetic variation in the Middle East, we aggregated whole exome and genome sequencing data from 2116 individuals in the Middle East and established the Middle East Variation (MEV) database. Of the high-impact coding (missense and loss of function) variants in this database, 53% were absent from the most comprehensive Genome Aggregation Database (gnomAD), thus representing a unique Middle Eastern variation dataset which might directly impact clinical variant interpretation. We highlight 39 variants with minor allele frequency >1% in the MEV database that were previously reported as rare disease variants in ClinVar and the Human Gene Mutation Database (HGMD). Furthermore, the MEV database consisted of 281 putative homozygous loss of function (LoF) variants, or complete knockouts, of which 31.7% (89/281) were absent from gnomAD. This set represents either complete knockouts of 83 unique genes in reportedly healthy individuals, with implications regarding disease penetrance and expressivity, or might affect dispensable exons, thus refining the clinical annotation of those regions. Intriguingly, 24 of those genes have several clinically significant variants reported in ClinVar and/or HGMD. Our study shows that genetic variation in the Middle East improves functional annotation and clinical interpretation of the genome and emphasizes the need for expanding sequencing studies in the Middle East and other underrepresented populations.

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“…The Qatari Cohort: The Qatar Genome Program (QGP) [21] is a population-based project launched by the Qatar Foundation to generate a large-scale whole-genome sequence (WGS) dataset, in combination with comprehensive phenotypic information collected by the Qatar Biobank (QBB) [22]. All subjects included in the analysis were of Qatari Middle Eastern Arabian ancestry [23]. In this study, we use a cohort of 14,398 individuals with an average coverage of 30X.…”

Section: Population Descriptionmentioning

confidence: 99%

“…We used data from the gnomAD v3.1 [35] call set, including 1000Genomes project samples and extracted information on the EUR, AFR and SAS superpopulations subset. The EUR subset was used as reference for the Italian samples [36], while the AFR and SAS subsets for the Qatari cohort [23]. We defined two different levels of comparison: at the ancestry level, in which we selected all genes showing concordant selective signals between our study cohorts and their closest ancestry population, and at the population level, in which we selected only genes showing different behaviour between our target population and the reference.…”

Section: Genes Selection and Prioritization Analysesmentioning

confidence: 99%

Poking COVID-19: Insights on Genomic Constraints among Immune-Related Genes between Qatari and Italian Populations

Mbarek

Cocca

Al-Sarraj

et al. 2021

Genes

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Host genomic information, specifically genomic variations, may characterize susceptibility to disease and identify people with a higher risk of harm, leading to better targeting of care and vaccination. Italy was the epicentre for the spread of COVID-19 in Europe, the first country to go into a national lockdown and has one of the highest COVID-19 associated mortality rates. Qatar, on the other hand has a very low mortality rate. In this study, we compared whole-genome sequencing data of 14398 adults and Qatari-national to 925 Italian individuals. We also included in the comparison whole-exome sequence data from 189 Italian laboratory-confirmed COVID-19 cases. We focused our study on a curated list of 3619 candidate genes involved in innate immunity and host-pathogen interaction. Two population-gene metric scores, the Delta Singleton-Cohort variant score (DSC) and Sum Singleton-Cohort variant score (SSC), were applied to estimate the presence of selective constraints in the Qatari population and in the Italian cohorts. Results based on DSC and SSC metrics demonstrated a different selective pressure on three genes (MUC5AC, ABCA7, FLNA) between Qatari and Italian populations. This study highlighted the genetic differences between Qatari and Italian populations and identified a subset of genes involved in innate immunity and host-pathogen interaction.

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Thousands of Qatari genomes inform human migration history and improve imputation of Arab haplotypes

Cited by 27 publications

References 78 publications

Qatar genome: Insights on genomics from the Middle East

Qatar genome: Insights on genomics from the Middle East

Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome

Poking COVID-19: Insights on Genomic Constraints among Immune-Related Genes between Qatari and Italian Populations

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