Younes Mokrab
A5016998478- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Genomic variations and chromosomal abnormalities
- Ion channel regulation and function
- Epigenetics and DNA Methylation
- Bioinformatics and Genomic Networks
- Cancer Immunotherapy and Biomarkers
- Lipid Membrane Structure and Behavior
- Cancer Genomics and Diagnostics
- Cardiac electrophysiology and arrhythmias
- Diet and metabolism studies
- Genetic Syndromes and Imprinting
- Protein Structure and Dynamics
- Cancer-related molecular mechanisms research
- Functional Brain Connectivity Studies
- Electrochemical Analysis and Applications
- Genetics and Neurodevelopmental Disorders
- Ferroptosis and cancer prognosis
- RNA and protein synthesis mechanisms
- Forensic and Genetic Research
- Congenital heart defects research
- Neuroscience and Neuropharmacology Research
- Chronic Obstructive Pulmonary Disease (COPD) Research
- Immunotherapy and Immune Responses
- Single-cell and spatial transcriptomics
Weill Cornell Medical College in Qatar
2021-2025
Qatar University
2024-2025
Eli Lilly (United Kingdom)
2015-2024
Qatar Airways (Qatar)
2021-2024
Hamad bin Khalifa University
2021-2022
Sidra Medical and Research Center
2016-2022
University of Oxford
2008-2016
Eli Lilly (United States)
2014
University of Cambridge
2004-2011
National Institute of Biomedical Innovation, Health and Nutrition
2011
We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled TCGA. Across types, we identified six immune subtypes—wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant—characterized differences in macrophage or signatures, Th1:Th2 cell ratio, extent intratumoral heterogeneity, aneuploidy, neoantigen load, overall proliferation, expression immunomodulatory genes,...
Despite recent biomedical breakthroughs and large genomic studies growing momentum, the Middle Eastern population, home to over 400 million people, is underrepresented in human genome variation databases. Here we describe insights from Phase 1 of Qatar Genome Program with whole sequenced 6047 individuals Qatar. We identified more than 88 variants which 24 are novel 23 singletons. Consistent high consanguinity founder effects region, found that several rare deleterious were common Qatari...
Cancer immunotherapy is revolutionizing the clinical management of several tumors, but has demonstrated limited activity in breast cancer. The development more effective treatments hindered by incomplete knowledge genetic determinant immune responsiveness. To fill this gap, we mined copy number alteration, somatic mutation, and expression data from Genome Atlas (TCGA). By using RNA-sequencing 1,004 cancers, defined distinct phenotypes characterized progressive transcripts previously...
Objective The uptake carrier organic anion-transporting polypeptide 1B3 (OATP1B3, gene SLCO1B3) is involved in the hepatic clearance of xenobiotics including statins, taxanes, and mycophenolic acid. We thought to assess SLCO1B3 coding region for yet unidentified polymorphisms analyze their functional relevance. Methods used DNA ethnically diverse individuals polymerase chain reaction, determined by sequencing or temperature-dependent capillary electrophoresis. then created variant OATP1B3...
Abstract Clinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report genome-wide association study with 45 clinically relevant traits from the population of Qatar using whole genome sequencing approach discovery set 6218 individuals and replication 7768 subjects. Trait heritability more similar Qatari European populations ( r = 0.81) than Africans 0.44). identify 281 distinct...
Abstract Clinical implementation of pharmacogenomics will help in personalizing drug prescriptions and alleviate the personal financial burden due to inefficacy adverse reactions drugs. However, such is lagging many parts world, including Middle East, mainly lack data on distribution actionable pharmacogenomic variation these ethnicities. We analyzed 6,045 whole genomes from Qatari population for allele frequencies 2,629 variants 1,026 genes known affect 559 drugs or classes also performed a...
Genome sequencing of large biobanks from under-represented ancestries provides a valuable resource for the interrogation Mendelian disease burden at world population level, complementing small-scale familial studies. Here, we interrogate 6045 whole genomes Qatar-a Middle Eastern with high consanguinity and understudied mutational burden-enrolled national Biobank phenotyped 58 clinically-relevant quantitative traits. We examine curated set 2648 genes 20 panels, annotating known novel...
Abstract Arabic populations are underrepresented in large genome projects; therefore, the frequency of clinically actionable variants among Arabs is largely unknown. Here, we investigated genetic variation 14,392 whole genomes from Qatar Genome Program (QGP) across list 78 genes (v3.1) determined by American College Medical Genetics and Genomics (ACMG). Variants were categorized into one following groups: (1) Pathogenic (P), (2) Likely pathogenic (LP), (3) Rare uncertain significance with...
Arab populations are largely understudied, notably their genetic structure and history. Here we present an in-depth analysis of 6,218 whole genomes from Qatar, revealing extensive diversity as well ancestries representing the main founding genealogical lineages Qahtanite (Peninsular Arabs) Adnanite (General Arabs West Eurasian Arabs). We find that Peninsular closest relatives ancient hunter-gatherers Neolithic farmers Levant, founder experienced multiple splitting events 12-20 kya,...
Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by impaired social and communication skills, restricted interests, repetitive behaviors. The prevalence of ASD among children in Qatar was recently estimated to be 1.1%, though the genetic architecture underlying both greater Middle East has been largely unexplored. Here, we describe first genomic data release from BARAKA-Qatar Study-a nationwide program building broadly consented biorepository individuals with...
Predicting cognitive decline using MRI measures of brain volume is challenging. Normative models capture the evolution biomarkers over time in a healthy group, quantifying an individuals deviation from that norm. Here, we improve precision normative for hippocampal volume, key biomarker, by integrating multi-threshold polygenic scores (PGS) genetic predisposition to its variability. We built Gaussian Process Regression (GPR) on genetic, imaging, and demographic data 23,997 UK Biobank (UKBB)...
The Hv1 proton channel is evidently unique among voltage sensor domain proteins in mediating an intrinsic 'aqueous' H+ conductance (GAQ). Mutation of a highly conserved 'gating charge' residue the S4 helix (R1H) confers resting-state 'shuttle' (GSH) VGCs and Ci VSP, we now report that R1H sufficient to reconstitute GSH without abrogating GAQ. Second-site mutations S3 (D185A/H) (N4R) experimentally separate GAQ gating, which thermodynamically distinct initial final steps, respectively,...
In a clinical setting, DNA sequencing can uncover findings unrelated to the purpose of genetic evaluation. The American College Medical Genetics and Genomics (ACMG) recommends evaluation reporting 59 genes from clinic genomic sequencing. While prevalence secondary is available large population studies, these data lack Arab other Middle Eastern populations. Qatar Genome Program (QGP) generates whole-genome (WGS) combines it with phenotypic information create comprehensive database for...
Alcohol dehydrogenase 1B (ADH1B) is a primate-specific enzyme which, uniquely among the ADH class 1 family, highly expressed both in adipose tissue and liver. Its expression reduced obesity increased by insulin stimulation. Interference with ADH1B has also been reported to impair adipocyte function. To better understand role of adipocytes, we used CRISPR/Cas9 delete human stem cells (ASC). Cells lacking failed differentiate into mature adipocytes manifested minimal triglyceride accumulation...
The guanidino-group modifying enzyme (GME) superfamily contains many drug targets, including metabolic enzymes from pathogenic microorganisms as well key regulatory proteins higher eukaryotes. These enzymes, despite their diverse sequences, adopt the common alpha/beta propeller fold and catalyze modification of (methylated) guanidino groups. Our structural superposition structure-based alignment for GMEs have identified residues that are involved in catalysis substrate binding. We shown...
Membrane protein function and stability has been shown to be dependent on the lipid environment. Recently, we developed a high-throughput computational approach for prediction of membrane protein/lipid interactions. In current study, enhanced this with addition new measure distortion caused by proteins bilayer. This is illustrated considering effect tail length headgroup charge integral MscS FLAP, voltage sensing domain from channel KvAP. Changing chain lipids alters extent but not pattern...