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Cynthia Al Hageh,1,* Stephanie Chacar,2,* Michella Ghassibe-Sabbagh,3 Daniel E Platt,4 Andreas Henschel,5 Hamdan Hamdan,2 Dominique Gauguier,6,7 Yara El Murr,3 Eman Alefishat,8,9 Elie Chammas,10 Siobhán O’Sullivan,1 Antoine Abchee,11 Moni Nader,2,9 Pierre A Zalloua1,9,12 1Department of Molecular Biology and Genetics, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 2Department of Physiology and Immunology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 3Department of Natural Sciences, School of Arts and Sciences, Lebanese American University, Beirut, Lebanon; 4Computational Biology Center, IBM TJ Watson Research Centre, Yorktown Hgts, NY, USA; 5Department of Electrical Engineering and Computer, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 6Université Paris Cité, INSERM UMR 1124, Paris, 75006, France; 7McGill University and Genome Quebec Innovation Centre, Montreal, QC, H3A 0G1, Canada; 8Department of Pharmacology, College of Medicine and Health Sciences, Khalifa University of Science and Technology, Abu Dhabi, United Arab Emirates; 9Center for Biotechnology, Khalifa University of Science and Technology, Abu Dhabi, 127788, United Arab Emirates; 10School of Medicine, Lebanese University, Beirut, Lebanon; 11Sheikh Shakhbout Medical City, Abu Dhabi, United Arab Emirates; 12Harvard T.H. Chan School of Public Health, Boston, MA, USA*These authors contributed equally to this workCorrespondence: Pierre A Zalloua; Moni Nader, College of Medicine and Health Sciences, Khalifa University for Science and Technology, PO Box 127788, Abu Dhabi, United Arab Emirates, Email pierre.zalloua@ku.ac.ae; moni.nader@ku.ac.aeBackgrounds and Aims: The role of Lipoprotein(a) (Lp(a)) in increasing the risk of cardiovascular diseases is reported in several populations. The aim o

Global and local whole genome sequencing of SARS-CoV-2 enables the tracing of domestic and international transmissions. We sequenced Viral RNA from 37 sampled Covid-19 patients with RT-PCR-confirmed infections across the UAE and developed time-resolved phylogenies with 69 local and 3,894 global genome sequences. Furthermore, we investigated specific clades associated with the UAE cohort and, their global diversity, introduction events and inferred domestic and international virus transmissions between January and June 2020. The study comprehensively characterized the genomic aspects of the virus and its spread within the UAE and identified that the prevalence shift of the D614G mutation was due to the later introductions of the G-variant associated with international travel, rather than higher local transmissibility. For clades spanning different emirates, the most recent common ancestors pre-date domestic travel bans. In conclusion, we observe a steep and sustained decline of international transmissions immediately following the introduction of international travel restrictions.

The interplay between the compositional changes in the gastrointestinal microbiome, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) susceptibility and severity, and host functions is complex and yet to be fully understood. This study performed 16S rRNA gene-based microbial profiling of 143 subjects. We observed structural and compositional alterations in the gut microbiota of the SARS-CoV-2-infected group in comparison to non-infected controls. The gut microbiota composition of the SARS-CoV-2-infected individuals showed an increase in anti-inflammatory bacteria such as Faecalibacterium (p-value = 1.72 × 10–6) and Bacteroides (p-value = 5.67 × 10–8). We also revealed a higher relative abundance of the highly beneficial butyrate producers such as Anaerostipes (p-value = 1.75 × 10–230), Lachnospiraceae (p-value = 7.14 × 10–65), and Blautia (p-value = 9.22 × 10–18) in the SARS-CoV-2-infected group in comparison to the control group. Moreover, phylogenetic investigation of communities by reconstructing unobserved state (PICRUSt) functional prediction analysis of the 16S rRNA gene abundance data showed substantial differences in the enrichment of metabolic pathways such as lipid, amino acid, carbohydrate, and xenobiotic metabolism, in comparison between both groups. We discovered an enrichment of linoleic acid, ether lipid, glycerolipid, and glycerophospholipid metabolism in the SARS-CoV-2-infected group, suggesting a link to SARS-CoV-2 entry and replication in host cells. We estimate the major contributing genera to the four pathways to be Parabacteroides, Streptococcus, Dorea, and Blautia, respectively. The identified differences provide a new insight to enrich our understanding of SARS-CoV-2-related changes in gut microbiota, their metabolic capabilities, and potential screening biomarkers linked to COVID-19 disease severity.

The ethnic composition of the population of a country contributes to the uniqueness of each national DNA sequencing project and, ideally, individual reference genomes are required to reduce the confounding nature of ethnic bias. This work represents a representative Whole Genome Sequencing effort of an understudied population. Specifically, high coverage consensus sequences from 120 whole genomes and 33 whole exomes were used to construct the first ever population specific major allele reference genome for the United Arab Emirates (UAE). When this was applied and compared to the archetype hg19 reference, assembly of local Emirati genomes was reduced by ∼19% (i.e., some 1 million fewer calls). In compiling the United Arab Emirates Reference Genome (UAERG), sets of annotated 23,038,090 short (novel: 1,790,171) and 137,713 structural (novel: 8,462) variants; their allele frequencies (AFs) and distribution across the genome were identified. Population-specific genetic characteristics including loss-of-function variants, admixture, and ancestral haplogroup distribution were identified and reported here. We also detect a strong correlation between F and admixture components in the UAE. This baseline study was conceived to establish a high-quality reference genome and a genetic variations resource to enable the development of regional population specific initiatives and thus inform the application of population studies and precision medicine in the UAE. ST

© Copyright © 2020 Daw Elbait, Henschel, Tay and Al Safar. Whole genome sequences (WGS) of four nationals of the United Arab Emirates (UAE) at an average coverage of 33X have been completed and described. The selection of suitable subpopulation representatives was informed by a preceding comprehensive population structure analysis. Representatives were chosen based on their central location within the subpopulation on a principal component analysis (PCA) and the degree to which they were admixed. Novel genomic variations among the different subgroups of the UAE population are reported here. Specifically, the WGS analysis identified 4,161,067–4,798,806 variants in the four individual samples, where approximately 80% were single nucleotide polymorphisms (SNPs) and 20% were insertions or deletions (indels). An average of 2.75% was found to be novel variants according to dbSNP (build 151). This is the first report of structural variants (SV) from WGS data from UAE nationals. There were 15,677–20,339 called SVs, of which around 13.5% were novel. The four samples shared 1,399,178 variants, each with distinct variants as follows: 1,085,524 (for the individual denoted as UAE S011), 1,228,559 (UAE S012), 791,072 (UAE S013), and 906,818 (UAE S014). These results show a previously unappreciated population diversity in the region. The synergy of WGS and genotype array data was demonstrated through variant annotation of the former using 2.3 million allele frequencies for the local population derived from the latter technology platform. This novel approach of combining breadth and depth of array and WGS technologies has guided the choice of population genetic representatives and provides complementary, regionalized allele frequency annotation to new genomes comprising millions of loci.

© Copyright © 2020 Tay, Henschel, Daw Elbait and Al Safar. With high consanguinity rates on the Arabian Peninsula, it would not have been unexpected if the population of the United Arab Emirates (UAE) was shown to be relatively homogenous. However, this study of 1000 UAE nationals provided a contrasting perspective, one of a relatively heterogeneous population. Located at the apex of Europe, Asia, and Africa, the observed diversity could be explained by a plethora of migration patterns since the first Out-of-Africa movement. A strategy to explore the extent of genetic variation of the population of the UAE is presented. The first step involved a comprehensive population stratification study that was instructive for subsequent whole genome sequencing (WGS) of suitable representatives (which is described elsewhere). When these UAE data were compared to previous smaller studies from the region, the findings were consistent with a population that is a diverse and admixed group of people. However, rather than sharp and distinctive clusters, cluster analysis reveals low levels of stratification throughout the population. UAE emirates exhibit high within-Emirate-distance/among-Emirate distance ratios. Supervised admixture analysis showed a continuous gradient of ancestral populations, suggesting that admixture on the south eastern tip of the Arabian Peninsula occurred gradually. When visualized using a unique technique that combined admixture ratios and principal component analysis (PCA), unappreciated diversity was revealed while mitigating projection bias of conventional PCA. We observe low population stratification in the UAE in terms of homozygosity versus separation cluster coefficients. This holds for the UAE in a global context as well as for isolated cluster analysis of the Emirati birthplaces. However, the subtle clustering observed in the Emirates reflects geographic proximity and historic migration events. The analytical strategy used here highlights the complem