Genomics of Egyptian Healthy Volunteers: The EHVol Study (original) (raw)
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The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: defining a healthy volunteer cohort
npj Genomic Medicine
The integration of comprehensive genomic and phenotypic data from diverse ethnic populations offers unprecedented opportunities toward advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases are not representative of the global human population, making variant interpretation challenging, especially in underrepresented populations, such as the North African population. To address this, the Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project launched a study comprising 1000 individuals free of cardiovascular disease (CVD). Here, we present the first 391 Egyptian healthy volunteers recruited to establish a pilot phenotyped control cohort. All individuals underwent detailed clinical investigation, including cardiac magnetic resonance imaging (MRI), and were sequenced using a targeted panel of 174 genes with reported roles in inherited cardiac conditions. We identified 1262 variants in 27 cardiomyopathy genes of which 15.1% were no...
A personal and population-based Egyptian genome reference
2019
The human genome is composed of 23 chromosomal DNA sequences of bases A, C, G and T-the blueprint to implement the molecular functions that are at the basis of every individual's life. Deciphering the first human genome was a consortium effort that took more than a decade and cost about 3 billion dollars. With latest technological advances, determining an individual's entire personal genome at manageable cost and effort comes into reach. Although the benefit of all-encompassing genetic information that entire genomes provide is widely noted, so far only a small number of de novo assembled human genomes have been reported. Even less have been characterized and complemented with respect to population-specific variation. Here we combine long-and short-read whole genome next-generation sequencing data together with the recent assembly approaches for the first de novo assembly of the genome of an Egyptian individual, which we merged with Egyptian variant data into a population reference genome. The resulting genome assembly demonstrates overall well-balanced quality metrics and comes along with high quality variant phasing into maternal and paternal haplotypes. Further, we assayed population-specific variations genome-wide within a representative cohort of more than 100 Egyptian individuals. By annotation of these genetic data and integration with public databases we showcase genetic variants that alter protein sequence and that are linked to allelic gene expression. This is one of a handful of studies that comprehensively describe a population reference genome based on a high-quality personal genome and which highlights populationspecific variants of interest. It is a proof-of-concept to be considered by the many national genome initiatives underway. And, more importantly, we anticipate that the Egyptian reference genome will be a valuable resource for precision medicine initiatives targeting the Egyptian population and beyond. All summary data of the Egyptian genome reference is available at www.egyptian-genome.org. The Egyptian genome reference will be publicly available upon journal publication. Main In the last years, several high-quality de novo human genome assemblies (1-3) and, more recently, pan-genomes (4) extended human sequence information and improved the de facto reference genome. At present, many national genome initiatives are established which aim to genetically characterize human populations (5). Population-specific genetic variation as part of an individual's personal genetic variation is indispensable for precision medicine (PM). Currently, genomics-based PM compares the patients' genetic make-up to a reference genome, a genome model inferred from people of mostly European descent, to detect risk mutations that are related to disease. However, genetic and epidemiologic studies have long recognized the importance of ancestral origin in conferring risk genes for disease. Risk alleles and structural variants (6) can be missing from the reference genome or can have different population frequencies such that alternative pathways become disease related in patients of different ancestral origin, which motivates to establish national genome projects. At present, there are several population-based sequencing efforts that aim at
Cardiovascular journal of Africa
Cardiovascular diseases, principally ischaemic heart disease and stroke, are the leading causes of global mortality and morbidity. Together with other non-communicable diseases, they account for more than 60% of global deaths and pose major social, economic and developmental challenges worldwide. In Africa, there is now compelling evidence that the major cardiovascular disease (CVD) risk factors are on the rise, and so are the related fatal and non-fatal sequelae, which occur at significantly younger ages than seen in high-income countries. In order to tackle this rising burden of CVD, the H3Africa Cardiovascular Working Group will hold an inaugural workshop on 30 May 2014 in Cape Town, South Africa. The primary workshop objectives are to enhance our understanding of the genetic underpinnings of the common major CVDs in Africa and strengthen collaborations among the H3Africa teams and other researchers using novel genomic and epidemiological tools to contribute to reducing the burde...
Cardiovascular diseases, principally ischaemic heart disease and stroke, are the leading causes of global mortality and morbidity. Together with other non-communicable diseases, they account for more than 60% of global deaths and pose major social, economic and developmental challenges worldwide. In Africa, there is now compelling evidence that the major cardiovascular disease (CVD) risk factors are on the rise, and so are the related fatal and non-fatal sequelae, which occur at significantly younger ages than seen in high-income countries. In order to tackle this rising burden of CVD, the H3Africa Cardiovascular Working Group will hold an inaugural workshop on 30 May 2014 in Cape Town, South Africa. The primary workshop objectives are to enhance our understanding of the genetic underpinnings of the common major CVDs in Africa and strengthen collaborations among the H3Africa teams and other researchers using novel genomic and epidemiological tools to contribute to reducing the burden of CVD on the continent. department of medicine, university College hospital, university of ibadan, ibadan, nigeria Mayowa O Owolabi, Dr Med, mayowaowolabi@yahoo.com Center for Translation Research and Implementation science, national heart, lung, and Blood institute, national institutes of health, Bethesda, md, usa George A Mensah, MD, george.mesah@nih.gov Cristina Rabadan-Diehl, MD division of kidney, urologic, and hematologic diseases, national institute of diabetes and digestive and kidney diseases, national institutes of health, Bethesda, md, usa Paul L Kimmel, MD Rebekah Rasooly, MD university of ghana medical school, accra, ghana Dwomoa Adu, MD sydney Brenner institute for molecular Bioscience, university of the witwatersrand; division of human genetics, nhls and school of pathology, Faculty of health sciences, university of witwatersrand, Johannesburg, south africa Michele Ramsay, PhD national institute of neurological disorders and stroke, national institutes of health, Bethesda, md, usa Salina P Waddy, MD department of neurology, medical university of south Carolina, Charleston, sC, usa Bruce Ovbiagele, MD department of nutrition, harvard school of public health,
Genomics and Epigenomics of Congenital Heart Defects: Expert Review and Lessons Learned in Africa
Omics : a journal of integrative biology, 2018
Congenital heart defects (CHD) are structural malformations found at birth with a prevalence of 1%. The clinical trajectory of CHD is highly variable and thus in need of robust diagnostics and therapeutics. Major surgical interventions are often required for most CHDs. In Africa, despite advances in life sciences infrastructure and improving education of medical scholars, the limited clinical data suggest that CHD detection and correction are still not at par with the rest of the world. But the toll and genetics of CHDs in Africa has seldom been systematically investigated. We present an expert review on CHD with lessons learned on Africa. We found variable CHD phenotype prevalence in Africa across countries and populations. There are important gaps and paucity in genomic studies of CHD in African populations. Among the available genomic studies, the key findings in Africa were variants in GATA4 (P193H), MTHFR 677TT, and MTHFR 1298CC that were associated with atrial septal defect, v...
Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. At 30x sequencing coverage, we identified 12 SNPs that were shared in most of the subjects associated with obesity which are concordant with their clinical diagnosis. Also, we found mtDNA mutation A4282G is common in all the samples and this is associated with chronic progressive external ophthalmoplegia (CPEO). Haplogroup and Admixture analyses revealed that most Egyptian samples are close to the other north Mediterranean, Middle Eastern, and European, respectively, possibly reflecting the into-Africa influx of human migration. In conclusion, we present wholegenome sequences of nine Egyptian females with personal clinical information that cover the diverse regions of Egypt. Although limited in sample size, the whole genomes data provides possible geno-phenotype candidate markers that are relevant to the region's diseases.
Middle Eastern Genetic Variation Improves Clinical Annotation of the Human Genome
2021
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...
2020
Egyptians are at a crossroad between Africa and Eurasia, providing useful genomic resources for analyzing both genetic and environmental factors for future personalized medicine. Two personal Egyptian whole genomes have been published previously by us and here nine female whole genome sequences with clinical information have been added to expand the genomic resource of Egyptian personal genomes. Here we report the analysis of whole genomes of nine Egyptian females from different regions using Illumina short-read sequencers. At 30x sequencing coverage, we identified 12 SNPs that were shared in most of the subjects associated with obesity which are concordant with their clinical diagnosis. Also, we found mtDNA mutation A4282G is common in all the samples and this is associated with chronic progressive external ophthalmoplegia (CPEO). Haplogroup and Admixture analyses revealed that most Egyptian samples are close to the other north Mediterranean, Middle Eastern, and European, respectively, possibly reflecting the into-Africa influx of human migration. In conclusion, we present whole-genome sequences of nine Egyptian females with personal clinical information that cover the diverse regions of Egypt. Although limited in sample size, the whole genomes data provides possible genophenotype candidate markers that are relevant to the region’s diseases.
2019
BackgroundGenome sequencing coupled with electronic heath record data can uncover medically important genetic variation. Interpretation of rare genetic variation and its role in mediating cardiovascular phenotypes is confounded by variants of uncertain significance.Methods and ResultsWe analyzed the whole genome sequence of 900 racially and ethnically diverse biobank participants selected from a single US center. Participants were equally divided among European, African, Hispanic, and mixed race/ethnicities. We evaluated the American College of Medical Genetics and Genomics medically actionable list of 59 genes focusing on the cardiac genes. Variation was interpreted using the most recent reports in ClinVar, a database of medically relevant human variation. We identified 19 individuals with pathogenic/likely pathogenic variants in cardiac actionable genes (2%) and found evidence for clinical correlates in the electronic health record. African ancestry participants had more variants ...
Role of genomics in cardiovascular medicine
World journal of cardiology, 2010
As all branches of science grow and new experimental techniques become readily accessible, our knowledge of medicine is likely to increase exponentially in the coming years. Recently developed technologies have revolutionized our analytical capacities, leading to vast knowledge of many genes or genomic regions involved in the pathogenesis of congenital heart diseases, which are often associated with other genetic syndromes, coronary artery disease and non-ischemic cardiomyopathies and channelopathies. The knowledge-base of the genesis of cardiovascular diseases is likely going to be further revolutionized in this new era of genomic medicine. Here, we review the advances that have been made over the last several years in this field and discuss different genetic mechanisms that have been shown to underlie a variety of cardiovascular diseases.