Burden of Mendelian disorders in a large Middle Eastern biobank.

Background: Genome sequencing of large biobanks from under-represented ancestries provides a valuable resource for the interrogation of Mendelian disease burden at world population level, complementing small-scale familial studies.

Methods: Here, we interrogate 6045 whole genomes from Qatar-a Middle Eastern population with high consanguinity and understudied mutational burden-enrolled at the national Biobank and phenotyped for 58 clinically-relevant quantitative traits. We examine a curated set of 2648 Mendelian genes from 20 panels, annotating known and novel pathogenic variants and assessing their penetrance and impact on the measured traits.

Ancestry-related distribution of Runs of homozygosity and functional variants in Qatari population.

Background: Describing how genetic history shapes the pattern of medically relevant variants could improve the understanding of how specific loci interact with each other and affect diseases and traits prevalence. The Qatari population is characterized by a complex history of admixture and substructure, and the study of its population genomic features would provide valuable insights into the genetic landscape of functional variants. Here, we analyzed the genomic variation of 186 newly-genotyped healthy individuals from the Qatari peninsula.

Qatar genome: Insights on genomics from the Middle East.

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.

The QChip1 knowledgebase and microarray for precision medicine in Qatar.

Risk genes for Mendelian (single-gene) disorders (SGDs) are consistent across populations, but pathogenic risk variants that cause SGDs are typically population-private. The goal was to develop "QChip1," an inexpensive genotyping microarray to comprehensively screen newborns, couples, and patients for SGD risk variants in Qatar, a small nation on the Arabian Peninsula with a high degree of consanguinity. Over 10 variants in 8445 Qatari were identified for inclusion in a genotyping array containing 165,695 probes for 83,542 known and potentially pathogenic variants in 3438 SGDs.

Actionable genomic variants in 6045 participants from the Qatar Genome Program.

In a clinical setting, DNA sequencing can uncover findings unrelated to the purpose of genetic evaluation. The American College of Medical Genetics and Genomics (ACMG) recommends the evaluation and reporting of 59 genes from clinic genomic sequencing. While the prevalence of secondary findings is available from large population studies, these data lack Arab and other Middle Eastern populations.

Discovering Novel Biochemical and Genetic Markers for Coronary Heart Disease in Qatari Individuals: The Initiative Qatar Cardiovascular Biorepository.

Background: We aimed to describe the creation and challenge of a DNA and plasma biorepository (Qatar Cardiovascular Biorepository) with linkage to the electronic health record of cardiovascular risk factors to facilitate discovery of novel genetic and proteomic biomarkers for coronary heart disease in Qatari individuals.

Methods: A prospective case-control study was conducted between October 2013 and February 2018. CHD was defined as a history of an acute coronary syndrome (myocardial infarction [MI]/unstable angina) or coronary revascularization.

Exome sequencing-based identification of novel type 2 diabetes risk allele loci in the Qatari population.

Background: Type 2 diabetes (T2D) susceptibility is influenced by genetic and lifestyle factors. To date, the majority of genetic studies of T2D have been in populations of European and Asian descent. The focus of this study is on genetic variations underlying T2D in Qataris, a population with one of the highest incidences of T2D worldwide.

Targeted sequencing identifies novel variants involved in autosomal recessive hereditary hearing loss in Qatari families.

Hereditary hearing loss is characterized by a very high genetic heterogeneity. In the Qatari population the role of GJB2, the worldwide HHL major player, seems to be quite limited compared to Caucasian populations. In this study we analysed 18 Qatari families affected by non-syndromic hearing loss using a targeted sequencing approach that allowed us to analyse 81 genes simultaneously.

Correction: Type 2 Diabetes Risk Allele Loci in the Qatari Population.

[This corrects the article DOI: 10.1371/journal.pone.

The Qatar genome: a population-specific tool for precision medicine in the Middle East.

Reaching the full potential of precision medicine depends on the quality of personalized genome interpretation. In order to facilitate precision medicine in regions of the Middle East and North Africa (MENA), a population-specific genome for the indigenous Arab population of Qatar (QTRG) was constructed by incorporating allele frequency data from sequencing of 1,161 Qataris, representing 0.4% of the population.

Type 2 Diabetes Risk Allele Loci in the Qatari Population.

Background: The prevalence of type 2 diabetes (T2D) is increasing in the Middle East. However, the genetic risk factors for T2D in the Middle Eastern populations are not known, as the majority of studies of genetic risk for T2D are in Europeans and Asians.

Methods: All subjects were ≥3 generation Qataris.

Genetic testing and genomic analysis: a debate on ethical, social and legal issues in the Arab world with a focus on Qatar.

In 2013 both Saudi Arabia and Qatar launched genome projects with the aim of providing information for better diagnosis, treatment and prevention of diseases and, ultimately to realize personalized medicine by sequencing hundred thousands samples. These population based genome activities raise a series of relevant ethical, legal and social issues general, related to the specific population structure as well as to the Islamic perspective on genomic analysis and genetic testing. To contribute to the debate, the Authors after reviewing the existing literature and taking advantage of their professional experience in the field and in the geographic area, discuss and provide their opinions.

The Molecular Basis of α-Thalassemia in the Qatari Pediatric Population.

α-Thalassemia (α-thal) is widely reported in the Arabian Peninsula as one of the main causes of asymptomatic microcytic hypochromic red blood cells with or without anemia in the pediatric population. This is the first study that provides information about the molecular basis of α-thal in the Qatari population. Qatari school children between the ages of 5 and 15, exhibiting laboratory findings suggestive of microcytic anemia were pooled, and those with a mean corpuscular volume (MCV) of <80.

Increased rate of deleterious variants in long runs of homozygosity of an inbred population from Qatar.

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.

The p.Cys169Tyr variant of connexin 26 is not a polymorphism.

Mutations in the GJB2 gene, which encodes the gap junction protein connexin 26 (Cx26), are the primary cause of hereditary prelingual hearing impairment. Here, the p.Cys169Tyr missense mutation of Cx26 (Cx26C169Y), previously classified as a polymorphism, has been identified as causative of severe hearing loss in two Qatari families.

Consanguinity and hereditary hearing loss in Qatar.

Qatar is a sovereign state located on the Eastern coast of the Arabian Peninsula in the Persian Gulf. Its native population consists of 3 major subgroups: people of Arabian origin or Bedouins, those from an Eastern or Persian ancestry and individuals with African admixture. Historically, all types of consanguineous marriages have been and still are common in the Qatari population, particularly among first and double-first cousins.

Hereditary hearing loss: a 96 gene targeted sequencing protocol reveals novel alleles in a series of Italian and Qatari patients.

Deafness is a really common disorder in humans. It can begin at any age with any degree of severity. Hereditary hearing loss is characterized by a vast genetic heterogeneity with more than 140 loci described in humans but only 65 genes so far identified.

Linkage study and exome sequencing identify a BDP1 mutation associated with hereditary hearing loss.

Nonsyndromic Hereditary Hearing Loss is a common disorder accounting for at least 60% of prelingual deafness. GJB2 gene mutations, GJB6 deletion, and the A1555G mitochondrial mutation play a major role worldwide in causing deafness, but there is a high degree of genetic heterogeneity and many genes involved in deafness have not yet been identified. Therefore, there remains a need to search for new causative mutations.

Exome sequencing identifies potential risk variants for Mendelian disorders at high prevalence in Qatar.

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.

GJB2 and GJB6 genes and the A1555G mitochondrial mutation are only minor causes of nonsyndromic hearing loss in the Qatari population.

Objective: This study reports results from the first survey of the genetic causes of nonsyndromic sensorineural hearing loss (NSHHL) in the Qatari population. DESIGN AND STUDY SAMPLES: Data were collected from 126 Qatari patients (58 males and 68 females) belonging to inbred families (56%), showing an autosomal recessive pattern of inheritance (96%). Fifty-three patients were less than 10 years old, 55 in the age range of 10 to 20 years, while 18 were aged between 20 and 30 years.

Neuronal ceroid lipofuscinosis in Qatar: report of a novel mutation in ceroid-lipofuscinosis, neuronal 5 in the Arab population.

This study sought to genetically define the first family diagnosed with neuronal ceroid lipofuscinosis from Qatar. Onset was in late infancy (3 years), and sequencing in the affected children revealed a novel homozygous c.613C>T change in exon 3 of ceroid-lipofuscinosis, neuronal 5, corresponding to a missense mutation of a conserved amino acid, p.

Lack of association between the Pro12Ala polymorphism of the PPAR-gamma 2 gene and type 2 diabetes mellitus in the Qatari consanguineous population.

Peroxisome proliferators-activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that serves as a master regulator for adipocytes-specific genes contributing to adipocytes differentiation, insulin sensitivity and lipid metabolism. The substitution of proline to alanine at codon 12 of the PPAR gamma 2 gene (Pro12Ala polymorphism) is most widely studied, and the associations with diabetes, obesity, and other clinical parameters have been reported and discussed in several ethnic groups. Among native Qatar ethnicity, however, there is no report about this polymorphism.