The Egyptian Collaborative Cardiac Genomics (ECCO-GEN) Project: defining a healthy volunteer cohort

Abstract 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 not captured in current global and regional genetic reference databases (here: gnomAD and Great Middle Eastern Variome). The ECCO-GEN project aims at defining the genetic landscape of an understudied population and providing individual-level genetic and phenotypic data to support future studies in CVD and population genetics.

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Genomics of Egyptian Healthy Volunteers: The EHVol Study

10.1101/680520 ◽

2019 ◽

Cited By ~ 1

Author(s):

Yasmine Aguib ◽

Mona Allouba ◽

Alaa Afify ◽

Sarah Halawa ◽

Mohamed ElKhateb ◽

...

Keyword(s):

Healthy Volunteers ◽

Variant Interpretation ◽

North African ◽

Underrepresented Populations ◽

Phenotypic Data ◽

Genomic Databases ◽

The North ◽

Ethnic Populations ◽

North African Population ◽

Diagnostic Technologies

ABSTRACTComprehensive genomic databases offer unprecedented opportunities towards effective tailored strategies for the prevention and treatment of disease. The integration of genomic and phenotypic data from diverse ethnic populations is also key to advancements in precision medicine and novel diagnostic technologies. Current reference genomic databases, however, are not representative of the global human population, making variant interpretation challenging and uncertain, especially in underrepresented populations such as the North African population. To address this, a study of 391 Egyptian healthy volunteers (EHVols) was initiated as a milestone towards establishing the 1000 Egyptian Genomes project.

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Identification and Characterization of the Most Common Genetic Variant Responsible for Acephalic Spermatozoa Syndrome in Men Originating from North Africa

International Journal of Molecular Sciences ◽

10.3390/ijms22042187 ◽

2021 ◽

Vol 22 (4) ◽

pp. 2187

Author(s):

Caroline Cazin ◽

Yasmine Boumerdassi ◽

Guillaume Martinez ◽

Selima Fourati Ben Mustapha ◽

Marjorie Whitfield ◽

...

Keyword(s):

Electron Microscopy ◽

Transmission Electron Microscopy ◽

North Africa ◽

Posterior Part ◽

North African ◽

The North ◽

Transmission Electron ◽

Variant Filtering ◽

North African Population ◽

Sperm Nuclei

Acephalic spermatozoa syndrome (ASS) is a rare but extremely severe type of teratozoospermia, defined by the presence of a majority of headless flagella and a minority of tail-less sperm heads in the ejaculate. Like the other severe monomorphic teratozoospermias, ASS has a strong genetic basis and is most often caused by bi-allelic variants in SUN5 (Sad1 and UNC84 domain-containing 5). Using whole exome sequencing (WES), we investigated a cohort of nine infertile subjects displaying ASS. These subjects were recruited in three centers located in France and Tunisia, but all originated from North Africa. Sperm from subjects carrying candidate genetic variants were subjected to immunofluorescence analysis and transmission electron microscopy. Moreover, fluorescent in situ hybridization (FISH) was performed on sperm nuclei to assess their chromosomal content. Variant filtering permitted us to identify the same SUN5 homozygous frameshift variant (c.211+1_211+2dup) in 7/9 individuals (78%). SUN5 encodes a protein localized on the posterior part of the nuclear envelope that is necessary for the attachment of the tail to the sperm head. Immunofluorescence assays performed on sperm cells from three mutated subjects revealed a total absence of SUN5, thus demonstrating the deleterious impact of the identified variant on protein expression. Transmission electron microscopy showed a conserved flagellar structure and a slightly decondensed chromatin. FISH did not highlight a higher rate of chromosome aneuploidy in spermatozoa from SUN5 patients compared to controls, indicating that intra-cytoplasmic sperm injection (ICSI) can be proposed for patients carrying the c.211+1_211+2dup variant. These results suggest that the identified SUN5 variant is the main cause of ASS in the North African population. Consequently, a simple and inexpensive genotyping of the 211+1_211+2dup variant could be beneficial for affected men of North African origin before resorting to more exhaustive genetic analyses.

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Disease-modifying therapy prescription patterns in people with multiple sclerosis by age

Therapeutic Advances in Neurological Disorders ◽

10.1177/17562864211006499 ◽

2021 ◽

Vol 14 ◽

pp. 175628642110064

Author(s):

Yinan Zhang ◽

Amber Salter ◽

Shan Jin ◽

William J. Culpepper ◽

Gary R. Cutter ◽

...

Keyword(s):

Multiple Sclerosis ◽

Disease Activity ◽

Age Groups ◽

The Elderly ◽

Department Of Veterans Affairs ◽

Real World Data ◽

Research Committee ◽

The North ◽

Disease Modifying ◽

Magnetic Resonance Imaging Mri

Background: Disease-modifying therapies (DMTs) for multiple sclerosis (MS) are approved for their ability to reduce disease activity, namely clinical relapses and signal changes on magnetic resonance imaging (MRI). Disease activity appears age dependent. Thus, the greatest benefit would be expected in younger people with MS (PwMS) whereas benefits in the elderly are uncertain. Methods: Real-world data were obtained from PwMS from the North American Research Committee on Multiple Sclerosis (NARCOMS) registry and the US Department of Veterans Affairs Multiple Sclerosis Surveillance Registry (MSSR). Results: 6948 PwMS were surveyed from NARCOMS, and the MSSR had 1719 participants. In younger adult PwMS 40-years old or less, 183 (61.4%) in NARCOMS and 179 (70.5%) in the MSSR were prescribed DMTs. Among PwMS over age 60, 1575 (40.1%) in NARCOMS and 239 (36.3%) in the MSSR were prescribed DMTs. More PwMS in the age group of 31–40 ( p = 0.035) and 41–50 ( p = 0.001) in the MSSR were using DMTs compared with PwMS of the same age groups in NARCOMS. Conclusion: These findings suggest that DMTs are under-utilized in the younger population and continue to be commonly prescribed in the elderly. Broader access may explain the higher prescription rate of DMTs in US veterans.

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Factors associated with human visceral leishmaniasis cases during urban epidemics in Brazil: a systematic review

Parasitology ◽

10.1017/s0031182021000019 ◽

2021 ◽

pp. 1-9

Author(s):

Cleya da Silva Santana Cruz ◽

David Soeiro Barbosa ◽

Vinícius Cunha Oliveira ◽

Diogo Tavares Cardoso ◽

Nathália Sernizon Guimarães ◽

...

Keyword(s):

Systematic Review ◽

Visceral Leishmaniasis ◽

Urban Areas ◽

Grey Literature ◽

Cochrane Library ◽

Positive Correlation ◽

Individual Level ◽

Factors Associated ◽

The North ◽

Unified Health System

Abstract Visceral leishmaniasis (VL) is endemic in 70 countries and has been reported in 12 countries of Latin America, with over 90% of the cases reported in Brazil, where epidemics have occurred since 1980. The objective of this review is to describe the factors associated with the occurrence of VL epidemics in humans in urban areas. A systematic review was conducted according to the PRISMA-P guidelines. The databases PubMed (by Medline), Cochrane Library, Embase, Amed, LILACS and grey literature [Google Scholar and handsearch of the database of the Information System for Notifiable Diseases (SINAN) of Brazil's Unified Health System] were used. The protocol was registered under PROSPERO (CRD42019128998). Climatic, environmental factors and indicators of urban social structure were described as influencing the outbreaks in the North and Northeast regions. Gender and age characteristics were related to a greater chance of developing VL in the Central-West, Northeast and Southeast regions. Vector indicators showed a positive correlation with the incidence of VL in studies in the Northeast region. In the Southeast and Northeast regions, studies revealed the presence of dogs with positive correlation with VL. Knowledge gaps remain regarding the contribution to the increase in the risk factors described in ecological approaches, as no analysis was performed at the individual level, and it is still necessary to discuss the influence of other associated elements in epidemic episodes in the spread of VL.

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Watching the war against Iraq through pan-Arab satellite TV

Pacific Journalism Review – Te Koakoa ◽

10.24135/pjr.v9i1.753 ◽

2003 ◽

Vol 9 (1) ◽

pp. 26-31 ◽

Cited By ~ 3

Author(s):

Mohamed El-Bendary

Keyword(s):

Arab World ◽

Middle Eastern ◽

Atlantic Coast ◽

News Coverage ◽

Al Jazeera ◽

The West ◽

Satellite Television ◽

The North ◽

Satellite Channels ◽

Flow Of Information

It was the first Gulf War in 1991 which led to the satellite television explosion in the Arab world. Arabs then knew about Iraq’s invasion of Kuwait through CNN. Today, Arab satellite channels reach almost every Arab capital and many Middle Eastern and African nations — from Mauritania on the Atlantic coast to Iran in the east, from Syria in the north to Djibouti in the south. This battle for the airwaves and boom in satellite channels in the Arab world has become both a tool for integration and dispersion. It is raising a glimpse of hope that the flow of information will no longer be pouring from the West to the East, but from the East to the West. Questions, however, remain about the credibility of news coverage by Arabic networks like the maverick Qatar-based al-Jazeera and whether Arab journalists adhere to journalistic norms upheld in the West.

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Job tasks and the comparative structure of income and employment: Routine task intensity and offshorability for the LIS*

International Journal of Comparative Sociology ◽

10.1177/0020715218765218 ◽

2018 ◽

Vol 59 (2) ◽

pp. 81-109 ◽

Cited By ~ 2

Author(s):

Matthew C Mahutga ◽

Michaela Curran ◽

Anthony Roberts

Keyword(s):

Work Hours ◽

Social Scientists ◽

Data Infrastructure ◽

Individual Level ◽

Job Tasks ◽

The North ◽

Income Polarization ◽

Comparative Structure ◽

Global North ◽

Country Specific

Comparative sociologists have long considered occupations to be a key source of inequality. However, data constraints make comparative research on two of the more important contemporary drivers of occupational stratification – globalization and technological change – relatively scarce. This article introduces a new dataset on occupational ‘routine task intensity’ (RTI) and ‘offshorability’ (OFFS) for use with the Luxembourg Income Study (LIS). To produce these data, we recoded 23 country-specific occupational schemes (74 LIS country-years) to the two-digit ISCO-88 scheme. When combined with the handful of LIS countries already reporting their occupations in ISCO-88, we produce individual level RTI and OFFS scores for 38 LIS countries and 160 LIS country-years. To assess the validity of these recodes, we compare average labor-income ratios predicted by recoded ISCO-88 occupational categories to those predicted by reported ISCO-88 occupational categories within countries that transitioned from country-specific to ISCO-88 codes over time. To assess the utility of these RTI and OFFS scores and advance the literature on income polarization, we analyze their association with work hours and labor incomes in the global North and South. Both covariates correlate with work hours in ways that are consistent with previous research and additional theoretical considerations. Moreover, we show that both RTI and OFFS contribute to income polarization directly in the North, but not in the South. This article generates a public good data infrastructure that will be of use to a wide variety of social scientists, and brings new evidence to bear on the question of income polarization in rich democracies.

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The Relevance of Socioeconomic and Health Policy Issues to Clinical Research: The Case of MRI and Neuroradiology

International Journal of Technology Assessment in Health Care ◽

10.1017/s0266462300006425 ◽

1989 ◽

Vol 5 (2) ◽

pp. 195-206 ◽

Cited By ~ 10

Author(s):

Eric B. Larson ◽

Daniel L. Kent

Keyword(s):

Public Policy ◽

New Technologies ◽

Medical Profession ◽

New Technology ◽

Sound Studies ◽

Leadership Role ◽

Early Evaluation ◽

Diagnostic Technology ◽

Magnetic Resonance Imaging Mri ◽

Diagnostic Technologies

Magnetic resonance imaging (MRI) is a high-cost, new technology with great potential for improving patient care. The lack of a coherent public policy for MRI, or its predecessor computed tomography (CT), has caused considerable problems. Lack of an enunciated public policy has led to inconsistent reimbursement and reimbursement levels that develop in haphazard ways. Furthermore, diffusion has been unpredictable and has led to geographical excesses and deficiencies.Technology assessments of MRI, although numerous, have used inconsistent criteria to rate MRI's clinical efficacy. The lack of methodologically sound studies of MRI severely hampered early evaluation. This article examines these problems and suggests that the medical profession take a stronger leadership role in developing policies for expensive, promising new diagnostic technologies. The profession should promote, demand, and perform rigorous clinical evaluations of new technologies, and help develop a consensus regarding the criteria for what constitutes a clinically valuable advance in diagnostic technology.

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The genetic landscape of Scotland and the Isles

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.1904761116 ◽

2019 ◽

Vol 116 (38) ◽

pp. 19064-19070 ◽

Cited By ~ 5

Author(s):

Edmund Gilbert ◽

Seamus O’Reilly ◽

Michael Merrigan ◽

Darren McGettigan ◽

Veronique Vitart ◽

...

Keyword(s):

Genetic Structure ◽

Population Genetic ◽

Complex Trait ◽

Effect Sizes ◽

Source Population ◽

Genotype Data ◽

The West ◽

Variant Discovery ◽

The North ◽

Genetic Landscape

Britain and Ireland are known to show population genetic structure; however, large swathes of Scotland, in particular, have yet to be described. Delineating the structure and ancestry of these populations will allow variant discovery efforts to focus efficiently on areas not represented in existing cohorts. Thus, we assembled genotype data for 2,554 individuals from across the entire archipelago with geographically restricted ancestry, and performed population structure analyses and comparisons to ancient DNA. Extensive geographic structuring is revealed, from broad scales such as a NE to SW divide in mainland Scotland, through to the finest scale observed to date: across 3 km in the Northern Isles. Many genetic boundaries are consistent with Dark Age kingdoms of Gaels, Picts, Britons, and Norse. Populations in the Hebrides, the Highlands, Argyll, Donegal, and the Isle of Man show characteristics of isolation. We document a pole of Norwegian ancestry in the north of the archipelago (reaching 23 to 28% in Shetland) which complements previously described poles of Germanic ancestry in the east, and “Celtic” to the west. This modern genetic structure suggests a northwestern British or Irish source population for the ancient Gaels that contributed to the founding of Iceland. As rarer variants, often with larger effect sizes, become the focus of complex trait genetics, more diverse rural cohorts may be required to optimize discoveries in British and Irish populations and their considerable global diaspora.

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