Clinical genetics and genomic medicine in Qatar

Molecular Genetics & Genomic Medicine, 2018

This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Nature Communications, 2021

Clinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report a genome-wide association study with 45 clinically relevant traits from the population of Qatar using a whole genome sequencing approach in a discovery set of 6218 individuals and replication in 7768 subjects. Trait heritability is more similar between Qatari and European populations (r = 0.81) than with Africans (r = 0.44). We identify 281 distinct variant-trait-associations at genome wide significance that replicate known associations. Allele frequencies for replicated loci show higher correlations with European (r = 0.94) than with African (r = 0.85) or Japanese (r = 0.80) populations. We find differences in linkage disequilibrium patterns and in effect sizes of the replicated loci compared to previous reports. We also report 17 novel and Qatari-predominate signals providing insights into the biological pathways regulating th...

2000

2021

Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is under-represented in the human genome variation databases. Here we describe insights from phase 1 of the Qatar Genome Program which whole genome sequenced 6,045 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. Insights into the genetic structure of the Qatari population revealed five non-admixed subgroups. Based on sequence data, we also reported the heritability and genetic marker associations for 45 clinical traits. These results highlight the value of our data as a resourc...

Nucleic Acids Research, 2006

The Arabs comprise a genetically heterogeneous group that resulted from the admixture of different populations throughout history. They share many common characteristics responsible for a considerable proportion of perinatal and neonatal mortalities. To this end, the Centre for Arab Genomic Studies (CAGS) launched a pilot project to construct the 'Catalogue ofTransmissionGeneticsin Arabs' (CTGA) database for genetic disorders in Arabs. Information in CTGA is drawn from published research and mined hospital records. The database offers web-based basic and advanced search approaches. In either case, the final search result is a detailed HTML record that includes text-, URL-and graphic-based fields. At present, CTGA hosts entries for 692 phenotypes and 235 related genes described in Arab individuals. Of these, 213 phenotypic descriptions and 22 related genes were observed in the Arab population of the United Arab Emirates (UAE). These results emphasize the role of CTGA as an essential tool to promote scientific research on genetic disorders in the region. The priority of CTGA is to provide timely information on the occurrence of genetic disorders in Arab individuals. It is anticipated that data from Arab countries other than the UAE will be exhaustively searched and incorporated in CTGA (http://www.cags.org.ae).

Genetic Disorders Among Arab Populations, 2010

This paper looks at some of the studies on genetic disorders conducted in Bahrain. The disorders coverd include: genetic blood disorders, metabolic disorders, chromosomal disorders, including Down syndrome, and cystic fibrosis. The rate of consanguinity in Bahrain and the results of premarital counseling are also discussed.

Human genetics, 2017

In this study, we report the experience of the only reference clinical next-generation sequencing lab in Saudi Arabia with the first 1000 families who span a wide-range of suspected Mendelian phenotypes. A total of 1019 tests were performed in the period of March 2016-December 2016 comprising 972 solo (index only), 14 duo (parents or affected siblings only), and 33 trio (index and parents). Multigene panels accounted for 672 tests, while whole exome sequencing (WES) represented the remaining 347 tests. Pathogenic or likely pathogenic variants that explain the clinical indications were identified in 34% (27% in panels and 43% in exomes), spanning 279 genes and including 165 novel variants. While recessive mutations dominated the landscape of solved cases (71% of mutations, and 97% of which are homozygous), a substantial minority (27%) were solved on the basis of dominant mutations. The highly consanguineous nature of the study population also facilitated homozygosity for many private...

Scientific Reports

Consanguineous populations of the Arabian Peninsula have been underrepresented in global efforts that catalogue human exome variability. We sequenced 291 whole exomes of unrelated, healthy native Arab individuals from Kuwait to a median coverage of 45X and characterised 170,508 singlenucleotide variants (SNVs), of which 21.7% were 'personal'. Up to 12% of the SNVs were novel and 36% were population-specific. Half of the SNVs were rare and 54% were missense variants. The study complemented the Greater Middle East Variome by way of reporting many additional Arabian exome variants. The study corroborated Kuwaiti population genetic substructures previously derived using genome-wide genotype data and illustrated the genetic relatedness among Kuwaiti population subgroups, Middle Eastern, European and Ashkenazi Jewish populations. The study mapped 112 rare and frequent functional variants relating to pharmacogenomics and disorders (recessive and common) to the phenotypic characteristics of Arab population. Comparative allele frequency data and carrier distributions of known Arab mutations for 23 disorders seen among Arabs, of putative OMIM-listed causal mutations for 12 disorders observed among Arabs but not yet characterized for genetic basis in Arabs, and of 17 additional putative mutations for disorders characterized for genetic basis in Arab populations are presented for testing in future Arab studies. Characterising the patterns of genetic variation within and among human populations is crucial to understand human evolutionary history and the genetic basis of disorders 1. Many global genome-wide genotyping and whole-genome sequencing studies (such as the Human Genome Diversity Project 1,2 , the 1000 Genomes Project (1KGP) 3,4 and the UK10K project 5) have been undertaken to catalogue genetic variation. Coding exonic regions, though estimated to encompass only approximately 1-2% of the genome, harbour the most functional variation and contain almost 85% of the known disease-causing pathogenic variants 6,7 ; therefore, several global whole-exome sequencing studies have also been undertaken 8-10. Such large-scale global projects have revealed that human populations harbour a large amount of rare variations which exhibit little homology between diverged populations 3,9-17 , Mendelian and rare genetic disorders are often associated with rare coding variants. Likewise, common markers associated with complex disorders too can vary in frequency across populations 18. Considering that population-specific differences in allele frequencies are of clinical importance, it is fundamental to catalogue them in diverse ethnic populations 19. The Arabian Peninsula holds a strategic place in the early human migration routes out of Africa 20-22. The Peninsula was instrumental in shaping the genetic map of current global populations because the first Eurasian populations were established here 23. The ancestry of indigenous Arabs can largely be traced back to ancient lineages of the Arabian Peninsula 23,24. The Arab population is heterogeneous but well-structured 3,24-26. For example, the Kuwaiti population comprises three genetic subgroups, namely KWP (largely of West Asian ancestry

BMC medical genomics, 2015

The biomedical research sector in Saudi Arabia has recently received special attention from the government, which is currently supporting research aimed at improving the understanding and treatment of common diseases afflicting Saudi Arabian society. To build capacity for research and training, a number of centres of excellence were established in different areas of the country. Among these, is the Centre of Excellence in Genomic Medicine Research (CEGMR) at King Abdulaziz University, Jeddah, with its internationally ranked and highly productive team performing translational research in the area of individualized medicine. Here, we present a panorama of the recent trends in different areas of biomedical research in Saudi Arabia drawing from our vision of where genomics will have maximal impact in the Kingdom of Saudi Arabia. We describe advances in a number of research areas including; congenital malformations, infertility, consanguinity and pre-implantation genetic diagnosis, cance...