Egypt Genome: Towards an African new genomic era

Graphical abstract

Highlights

• •Studying human genome is crucial to embrace precision medicine.
• •The Northern bias in research for the last two decades precluded diversity as other ancestries including Africans and Middle Eastern populations were overwhelmingly underrepresented in genome and variant databases.
• •Egypt Genome (EG) aims to study the genomics of modern and Ancient Egyptian populations and to delineate the genetic bridging between them.
• •The three main objectives of the project are building an Egyptian reference genome, studying genomes of ancient Egyptians and finding the genetic variants associated with common and rare diseases.
• •Leveraging genomic medicine to improve precision medicine strategies while building a solid foundation for large-scale genomic research capacity is the fundamental focus of EG.
• •The impact of EG is predicted to go beyond Egypt and Africa as it fills the knowledge gaps in health and disease genomics towards improved and sustainable genomic-driven healthcare systems for better outcomes.

Abstract

Background

Studying the human genome is crucial to embrace precision medicine through tailoring treatment and prevention strategies to the unique genetic makeup and molecular information of individuals. After human genome project (1990–2003) generated the first full sequence of a human genome, there have been concerns towards Northern bias due to underrepresentation of other populations. Multiple countries have now established national genome projects aiming at the genomic knowledge that can be harnessed from their populations, which in turn can serve as a basis for their health care policies in the near future.

Aim of review

The intention is to introduce the recently established Egypt Genome (EG) to delineate the genomics and genetics of both the modern and Ancient Egyptian populations. Leveraging genomic medicine to improve precision medicine strategies while building a solid foundation for large-scale genomic research capacity is the fundamental focus of EG.

Key scientific concepts

EG generated genomic knowledge is predicted to enrich the existing human genome and to expand its diversity by studying the underrepresented African/Middle Eastern populations. The insightful impact of EG goes beyond Egypt and Africa as it fills the knowledge gaps in health and disease genomics towards improved and sustainable genomic-driven healthcare systems for better outcomes. Promoting the integration of genomics into clinical practice and spearheading the implementation of genomic-driven healthcare and precision medicine is therefore a key focus of EG. Mining into the wealth of Ancient Egyptian Genomics to delineate the genetic bridge between the contemporary and Ancient Egyptian populations is another excitingly unique area of EG to realize the global vision of human genome.

Background

Studying the human genome is crucial to embrace precision medicine, which focuses on tailoring treatment and prevention strategies to the unique genetic makeup and molecular information of individuals. Integrating the genomic data into healthcare strategies provides insights into individual health, allows the choice of appropriate therapeutic strategies for numerous diseases and addresses long term future health expectations within the context of preventive medicine [1], [2].

The human genome project, completing the first genome sequence of a human twenty years ago, expanded the horizon of what is possible in the field of human genetics and literally created the concepts of human genomics and population genomics [3]. This was followed by several breakthroughs in sequencing technologies allowing the continuous accumulation of data from hundreds of thousands of human exomes and genomes in public databases over the last two decades [4], [5]. Multiple countries have now established national genome projects aiming at the genomic knowledge that can be harnessed from their populations, which in turn can serve as a basis for their health care policies in the near future [6], [7].

The genome is the complete set of information in an organism’s DNA and genomic medicine is defined as the interdisciplinary medical specialty that involves using genomic information about a human individual as part of his/her clinical care, such as for diagnostic or therapeutic decision-making, and including the health outcomes and policy implications of that clinical use (National Human Genome Research Institute; NHGRI definition) [8]. Genomic medicine applies the principles of evolution, developmental biology, functional genomics, and structural genomics within clinical care [9].

Gaining insight into the personal or individual genome, implies the identification of genetic variations and their relationship to health and disease states. Therefore, studying the sum of all genetic differences sometimes referred to as population genome or variome in a population is important. On one hand, it distinguishes between variants responsible for diseases or biological differences in response to medications; on the other hand, it identifies variants that do not adversely affect the biological functions of the individual [10].

Despite the breakthrough in sequencing techniques, genomic research in Egypt was restricted to studying the variations in the Egyptian population, such as single nucleotide polymorphisms [11], [12], and exonic genetic variants [13], [14], [15]. In addition, there was a recent trial to present an Egyptian genome reference (Egyptref) [16], yet the sample used was too small to represent the Egyptian population. Therefore, EG has a crucial role in establishing the field of clinical genomics and precision medicine in Egypt, Middle East and Africa. Benefiting from the revolutionary technological advances, EG focuses on studying the role of genomic variation in health and disease to inform the development of healthcare preventive, diagnostic and therapeutic strategies.

Home to more than 100 million people and uniquely located at the crossroads of the three oldest continents Africa, Asia and Europe, Egypt can tremendously contribute to filling gaps in the human genome database, shed light on relationships of Egyptian genomes to those of other populations and add key pieces to the map of population genomics thus providing invaluable insight into change of allele frequencies in relation to geography and time.

Africa, the birthplace of Homo sapiens, and the Middle East, one of the oldest inhabited regions of the world, contributed tremendously to human history. Furthermore, North-East Africa was most probably the crossing-point of the greatest out-of-Africa human migration. A recent study identified modern Egyptians as the African population whose genomes and haplotype frequencies most closely resemble those of non-African populations, thereby supporting the theory of out-of-Africa migration route of humans via Sinai, Egypt [17].

The Northern bias in research for the last two decades towards European ancestries precluded diversity as other ancestries including Africans and Middle Eastern populations were overwhelmingly underrepresented in genome and variant databases. The scarce genomic data have therefore undermined the usefulness and generalized applicability of the current genomic knowledge available to inform the development of disease preventive or therapeutic strategies [18], [19].

Additionally, the current paleogenomic landscape has limited representation of many ancestries. Significant disparities have been detected in the origin of the samples examined, as almost 70 % of ancient genomes are of European or Russian origin [20].

Strategically, knowledge, innovation, and science are the chief pillars of Egypt Vision 2030 which fundamentally focuses on utilizing the generated knowledge output to face challenges and meet national objectives [21].

Implementation

The Academy of Scientific Research and Technology (ASRT), a governmental body affiliated to the Ministry of Higher Education and Scientific Research (MHESR), brings together outstanding national scientists and overseas experts to deliberate country challenges, propose research studies and develop strategic basic plans to decipher optimal solutions.

In July 2020, ASRT announced a call for the national mega genome project to address the unmet needs of national human genomics. ASRT received several proposals from research coalitions that included most of the research entities in Egypt. A committee of Egyptian ex-pat experts in the genomics had evaluated the submitted proposals. The evaluation results were presented at the ASRT Board of Directors meeting held in October 2020. The board approved a national coalition of national Centers of Excellence led by the Egypt Center for Research and Regenerative Medicine (ECRRM), marking the official approval of the EG.

In March 2021, the EG contract was signed between ASRT, as the entity overseeing the execution and funding of the project, and ECRRM, being the project headquarters and the leading institution responsible for its execution, in collaboration with a number of academic centers that participate in recruitment, data collection, and targeted genomic analysis. These include governmental and non-governmental universities, research centers, and the National Museum of Egyptian Civilization (NMEC). The ASRT coordinates and provides financial and technical support for the project.

A state-of-the-art central laboratory for next generation sequencing was established at ECRRM in 2021. Several copies of various automated equipment were purchased and installed in the lab, including instruments for DNA extraction (chemagic™ 360, Perkin Elmer, Waltham, MA, USA), DNA quality assurance (Qubit 4 Fluorometer (Invitrogen, Carlsbad, CA, USA), NanoDrop™ One (Thermo Scientific, Waltham, MA, USA) andLabChip GX Touch (Perkin Elmer)), NGS library preparation (ultrasonicator M220 (Covaris, Woburn, MA, USA) andSciclone-G3 Liquid Handling Workstation (Revvity, USA)), and short NGS sequencing (NovaSeq 6000 and NextSeq 2000 (Illumina, San Diego, CA, USA)). Long NGS sequencing platforms (Oxford Nanopore, Oxford, UK) are also currently being imported for the project. The DNA sequence pipeline of the DRAGEN Bio-IT Platform (version 3.9.5, Illumina) is used to perform the primary bioinformatics analysis of the NGS sequencing data.A sample biobank and a data storage facility were established to serve sample and data storage, respectively. Furthermore, dedicated bioinformatics and clinical geneticist teams are also available for further analysis and interpretation of the sequencing variants for clinical and other purposes.

At the national level, the project is a well-coordinated effort among various Egyptian entities including several major Egyptian universities and scientific centers and this national collaboration is organized at different levels starting from laying down the main policies and regulations of the project, preparation of data input frameworks including individual recruitment, clinical data collection and sampling and up to data analysis, outcome measures formulation and reporting. The collaborating centers for the first phase of the project include Cairo University, Ain Shams University, National Research Centre, Alexandria University, Mansoura University, Nile Universityministry of health and population, National Museum of Egyptian Civilization (NMEC), Magdi Yacoub foundation and Shefaa Al-Orman hospital. ECRRM will be leading the collaborators, and will be the only one tasked with genome sequencing, bio-banking, data analysis and storage,

As for international collaborations, the project sought the support of many regional and international genome projects. Open channels of communication were established with the United Arab Emirates, Saudi Arabia and the UK genome projects and several visits of the working teams at the Egypt Genome were conducted to these projects to visualize all processes running on the ground, benefit from their experiences concerning the challenges encountered at different stages of their projects and to consult them about the unique challenges encountered in the Egypt Genome. Furthermore, multiple educational visits from active members of the UK genome project have been organized to Cairo over the last two years mainly to offer scientific materials and experiences concerning the genetic diagnosis of rare diseases.

Population variants derived from the project will be available to the wider scientific community through an accessible database for the project created specifically to host the apparently healthy Egyptian individuals’ data. Variants of clinical interest arising from the project will be further submitted to open access databases, such as dbSNP and ClinVar. VCF files of genomes of healthy individuals will be also available for selected international databases upon approval of the project scientific committee.

Many potential obstacles can occur along the course of the project. These include ethical concerns, financial concerns, logistical issues, data security concerns and emergency technical collapses. Arising ethical concerns will be handled completely by the specialized ethics committee of the project and the central ethics committee at the Egyptian Ministry of Health if needed. The project is guaranteed its financial support for the first phase until 2027 through the Egyptian Academy of Scientific Research and Technology. The financial support of the second phase until 2032 is approved by the Egyptian government, but the contract is yet to be signed. A complete risk management plan was prepared for logistical, technical and data security issues with very specific instructions to act upon when needed.

Vision and objectives

EG aims to establish an Egyptian reference genome based on whole genome data from 100,000 apparently healthy Egyptian individuals (a population-representative sample of one individual per thousand by the end of the project's second stage by 2032).

The first stage (5 years) will involve whole genome sequencing (WGS) of 20,000 apparently healthy Egyptians. Additionally, this stage will include WGS of 200 ancient Egyptian mummies. Moreover, it will comprise the genomic characterization of 8,000 diseased patients representing important common and rare diseases, cancers and infectious disorders among the Egyptian population.

The general objective of the project is to establish a genetic infrastructure, or reference genome, for the Egyptian population. The goal is to improve the health of Egyptians by delivering a precise health service driven by individual genomics.

The specific objectives of the project are: i) building an Egyptian reference genome that encompasses the genetic variants among contemporary Egyptians, ii) studying the genomes of ancient Egyptians and iii) researching/finding the genetic variants that are associated with common and rare diseases in Egyptian population. EG will generally lay the groundwork for background information and genetic infrastructure for the collective gene pool of the contemporary Egyptian population.

Structure and management system

EG board of directors

The Egypt Genome Board of Directors (Fig. 1), headed by the Minister of Higher Education and Scientific Research, is the governing authority of EG, developing the strategies and the general policy for the program, monitoring the progress of the project, implementing the required activities, and evaluating the performance of the participating research centers and the project achievements.

Fig. 1.

Egypt Genome Project structure. ECRRM: Egypt Center for Research and Regenerative Medicine;WGS: Whole Genome Sequencing;WES: Whole Exome Sequencing.

EG committees

There are various EG committees formed by the Board of Directors through issued Ministerial decrees defining the job description of each committee, as well as the members and their affiliations. All committees will report directly to the Board of Directors and continuously cooperate and communicate with ECRRM.EGcommittees include scientific, training &capacity building, ethical & legal, and social communication committees (Fig. 1).

Enhancing public interest in the project is an important target for the steering committees, particularly the Social and Communication Committee, which is tasked with promoting public engagement over different media platforms. The members of this committee are of different geographic and cultural backgrounds within Egypt and most of them are either public figures or experts in mass media and communications. Proper public engagement will serve various purposes including the facilitation of funding justification at the legislative and executive levels, the acceleration of the recruitment rates and the removal of myths and misinformation about genomics and genetics amongst the general population. As shown in Fig. 1, the scientific committee is monitoring the project implementation and progress mainly through its monthly meeting. In addition, a quarterly report is presented to the Egypt Genome Board who has the ability to add or exclude any partner based on achievement.

Egypt Center for Research and Regenerative Medicine (ECRRM)

ECRRM, the executive center of the project, was established in 2017 by a presidential decree as a national and regional reference center for infectious and public health diseases. ECRRM’s vision is to be an accredited, high-quality scientific research-based center of excellence in the field of advanced medical research and regenerative medicine and to participate in improving the healthcare of the Egyptian and Middle Eastern communities. The center is managed by a Board of Directors headed by the Chief of Staff of the Armed Forces and includes representation from the Ministries of Defense, Health and Population, and Higher Education and Scientific Research.

ECRRM has been uniquely positioned to be at the forefront of genomic research in Africa with its state-of-the-art infrastructure and robust capacity configuration, it stands as a fully equipped center for human genome sequencing research.

As to its molecular capacity, ECRRM boasts a range of genomic sequencing platforms ensuring versatility and precision in its research endeavors, including Illumina’s NovaSeq 6000 known for its high throughput capabilities. ECRRM computational capacity recognizes the challenge of handling big data generated by genome sequencing, hence it initiated the establishment of state-of-the-art data center equipped with high performance computing infrastructure to serve as a computational hub for EG to efficiently handle and analyze large scale genomic datasets.

Participating research institutions

The participating research institutions comprise various Egyptian governmental and non-governmental research institutions contributing to the execution of the EG plans. Their inclusion in the primary list of participating implementing entities was based on the acceptance of their submitted proposals in response to the ASRT EG call.

Grand design

Population reference genome

EG substantially focuses on strategically studying nationals from all Egyptian Governorates including urban and rural communities, while leveraging collaboration with many Universities and research institutions stretching across the country.

In the first stage (5 years) of EG, population reference genome sample will involve the recruitment, examination, blood sampling and whole genome sequencing of 20,000 apparently healthy Egyptian volunteers who, upon primary clinical assessment, are not diagnosed to have clinical disease and living in residential addresses in Egypt. Each apparently healthy citizen is given a non-zero selection probability (Fig. 2).

Fig. 2.

Grand Design of Egypt Genome Project.

Recruitment entails adults over 18 years of age with proportionate representation from urban and rural demographic districts, and from different age groups (30 % for 18–30 years old, 50 % for 30–45 years, 15 % for 45–60 years, and 5 % for 60 + years), and genders (females 49.48 %, males 50.52 %) according to the most recent Egyptian demographic profile [22]. Personal and familial data will be collected from each individual and a complete clinical examination will be performed, complemented by basic laboratory investigations. Personal data will include name, national ID, gender, date of birth, residential address, marital status, education and employment, while family history will include number of siblings in the family, birth rank of the studied subject, Parents’ age if living or age at death and its causes, origins (which governorate and nationalities) and parental consanguinity. Full clinical history including level of physical activity, current and previous disease, surgical procedures, health risks, such as smoking or occupational hazards and history of menstruation and pregnancy in females will be obtained. Detailed clinical examination will be further conducted including general (height, weight, hip and waist circumferences, body mass index, pulse and blood pressure) and different body systems examination (heart, abdomen, chest, extremities, head and neck and skin). In addition to the genomic sequencing, routine laboratory investigations, such as complete blood count, kidney and liver function tests, HbA1c and lipid profile will be further investigated for each individual.

Each of the 27 administrative governorates within Egypt has been given an assigned number of samples to be collected over the different stages of the project based on the population percentage of each in the latest census performed in Egypt in 2017 (https://censusinfo.capmas.gov.eg/metadata-en-v4.2/index.php/catalog/621). Smaller administrative units within each governorate including different urban, rural and even remote areas have also been assigned a specific number to be recruited within each stage of the project depending on their representative populations. Each apparently healthy Egyptian individual living within these districts is having a non-zero chance of being recruited, regardless of his/her skin color, ancestry or religion as long as he/she satisfies the inclusion criteria. A continuous monitoring of the recruited numbers will be conducted at ECRRM each month, and the satellite centers will be notified on regular basis about the numbers still needed from each geographical region.

Ancient Egyptian genome

The objective of the ancient DNA (aDNA) research track is to effectively participate in the EG network by generating genomic data from Egyptian biological remains, enabling the characterization of ancient human and microbial organisms. The data will feed into the EG database and will serve to illustrate the sequence variations among the ancient Egyptians. Through comparison to the contemporary data, this should not only give insight as to how the Egyptian gene pool fared through history, but also shed light on the interaction between the human host genomics and that of the infectious agents.

The proposed research track will provide further insights into ancient Egyptian life [23], [24]. Answers to the addressed questions will fill knowledge gaps in the fields of anthropology, archaeology, evolution, and history. The results are expected to elucidate the temporal changes in the gene pool of Egyptians by comparing the genomic data of ancient and contemporary Egyptians.

From another perspective, the project is predicted to have several outcomes that may have direct translational applications in the fields of biomedical sciences. The study of ancient human genomes will shed light on the molecular pathology of human disease and the interaction of the human genome with environmental agents, particularly the susceptibility or resistance to various infectious organisms, which is currently a core issue of precision medicine.

Disease genomics

EG aims to identify the genetic variants associated with cancer, common, rare, and infectious diseases in the Egyptian population.

Since the Egyptian health authorities recently recognized rare disorders as a national health priority given their chronic, progressive, and life-threatening aspects, the rare diseases group took priority in EG. In a trial to limit their incidence and complications, the project focuses in its first stage on rare diseases the majority of which has no existing effective cures with significant medical, social and economic burdens.

A multitude of undiagnosed phenotypes with suspected genetic underpinning will be sequenced. This inclusion of nominated rare disease subsets into EG has been reviewed and approved by EG Scientific and Ethics committees. The choice of the sequencing approach, whether whole exome sequencing (WES) or WGS, will be specified according to each disease group's phenotypic and genotypic characterization. An electronic data collection form has been specifically designed and implemented for all rare disease patients for clinical data recording, storage and future retrieval.

The diversifying goals and objectives of the Egypt Genome will allow for great malleability in the design and conduction of various research subprojects. Concerning the disease arm of the project, genetic diagnosis and clinical research studies will constitute a major category of our future scientific output. Egypt with its unique genetic disease characteristics and the high prevalence of recessive disorders due to the common practice of consanguineous marriage in the community is expected to provide a scientific wealth of genetic disease phenotypes and genotypes to be reported. Furthermore, data from mining the various carrier frequencies of pathogenic variants in different monogenic disorders genes in the healthy population will supplement the diagnostics studies in determining the burdens of these disorders in the Egyptian community over the long run.

Cancer research studies, whether prospective or retrospective, somatic or germline are currently being planned to cover the spectrum of genetic etiologies for the most prevalent malignancies in the Egyptian community. The first being currently conducted is a study for investigating the genetic background of germline and somatic samples of patients with hepatocellular carcinoma, one of the most prevalent due to the historical high rates of HCV in Egypt. The field of cancer genomics will also be supplemented with data from the apparently healthy individuals, which can serve both as a reference control group and as a source for future prospective studies to link their genotypes with their potential susceptibility to different types of cancers.

Population genomics studies will further address a broad spectrum of research targets, such as elucidating the genomic structure and variability of the Egyptian apparently healthy individuals, who will be properly distributed over all geographic regions within Egypt. Among the most important research areas to study, we will start with the admixture analysis, identity by descent, runs of homozygosity, mitochondrial and Y-chromosome haplotypes, HLA subtypes and population pharmacegenomic variations.

Ethical and Social considerations

EG will fully embrace ethical principles mandated by the Declaration of Helsinki for medical research Involving human subjects (World Medical Association, 2013) and the Egyptian law No. 214/2020 regulating the clinical research in Egypt. A standardized written informedconsent form is created for all voluntary participants in the population genome study. The consent form is formulated in Arabic with a simple language to be understood by the common person and will be complemented by an elaborate verbal explanation of the project, its adopted procedures and the potential consequences of being included. The consent explanation procedure will be undertaken by trained medical personnel at the recruiting centers.

The obtained information on the recruited as well as their genomic data or biological samples will be under strict confidentiality policies and will not be shared to any third parties. Furthermore, any published data arising from the project will be completely anonymized.

Regarding the unexpected genomic findings (secondary or incidental findings) for the apparently healthy individuals, the American College of Medical Genetics (ACMG) guidelines of reporting secondary findings [25] will be followed.

Challenges of the Egypt genome

Egypt is a developing country and is expected to have more challenges when conducting a project of this magnitude, at least compared to more advanced nations which have more experience and resources. Although many of the established research facilities within Egypt have both Sanger the NGS sequencing equipment together with the human expertise needed to run them, the genomic research landscape in Egypt is still beyond many regional nations with better resources. The Egypt Genome project is aiming to fill in this gap in both the genomic research and clinical landscapes. A central genomic well-equipped lab is already established and running. The project is well funded for the next five years by the Egyptian Academy of Science to conduct genomic research at the highest level and at the same time to serve thousands of Egyptian patients who need clinical genetic diagnosis.

Capacity building plans

One of the fundamental elements of EG is the cultivation of the next generation of genomic scientists and researchers. It grants an unprecedented opportunity for young researchers to develop, expand and enhance their genomics and bioinformatics knowledge and skills. As a national project with capacity-building at its core, it focuses on forming a critical mass of knowledgeable scientists and health specialists in genomics and molecular medicine and drive the healthcare sector in the precision medicine direction.

The scientific committee personnel, as well as, the current working teams at ECRRM are mostly members of top Egyptian universities and research centers. These personnel are either eminent scientists in the various fields of genomics or promising young researchers with the potential to develop and grow into eminent scientists. A program of continuous education for the young is further established and running at ECRRM to enhance their development and keep them up-to-date. Moreover, bidirectional visits to national and international collaborators for learning purposes are continuously being held.

On the societal front, public engagement and outreach is another crucial element of EG. Understanding the importance of connecting science and technology, EG is pursuing public engagement initiatives. The first genome day held in Cairo, March 2023 aimed at raising awareness of genomic research and its healthcare transformation impact among medical and public communities. The event demystified complex genomic concepts for attendees from diverse backgrounds with interactive sessions engaging leading scientists. The public engagement initiatives underscore EG commitment to fostering a broader understanding of genomics.

The tremendous investment directed towards EG aims to place Egypt as a regional hub for genomics and precision medicine in the Middle East and Africa. EG is therefore focused on developing solid infrastructure, attracting talented scientists and building sustainable long-term research capacity to realize this vision.

A review of national genome projects

Genomic sequencing has become increasingly applied globally in research as well as in clinical practice [26]. Many countries started the integration of genomics into healthcare with the establishment of several national genome projects (Table 1) [27], [28], [29], [30], [31], [32], [33], [34], [35], [36], [37], [38], [39], [40], [41], [42], [43], [44], [45], [46], [47], [48], [49], [50], [51], [52], [53], [54], [55], [56], [57], [58], [59], [60], [61], [62], [63], [64].

Table 1.

National Genome Projects.

	Country [project]	Aim	Funding/execution	Time	Reference
Europe
1	United Kingdom[100,000 genome project] [The UK Biobank]	Rare disease Cancer Cancer Common disease	Genomics England, Department of Health & Social Care, UK Ministry of Health Wellcome Trust, Medical Research Council, Department of Health, and others	2012–2018 2006-ongoing	(Turnbull, 2018) [27] https://www.ukbiobank.ac.uk/
2	France[The French plan for genomic medicine]	Cancer Rare disease Common disease Population database	Supported by the government and launched with public financing	2016–2025	(Lévy, 2016) [28]
3	Spain[Medical genome Project] [The Genoma 1000 Navarra Research Project (NAGEN 1000)]	Population database Rare disease Rare disease	European Regional Development Funds (ERDF) Navarra Government. Departamento de DesarrolloEconómico-Dirección General de Industria	2016- 2018-	(Kumar et al., 2016) [29] (Pasalodos et al., 2020) [30]
4	Iceland [Iceland genome project]	Population database Ongoing research	deCODE genetics (private funding)	1996-ongoing	(Gudbjartsson et al., 2015) [31]
5	Sweden[SweGen]	Population database	The Knut and Alice Wallenberg Foundation	2017-ongoing	(Ameur et al., 2017) [32]
6	Italy [Italian Genome project]	Reference genome Rare disease Cancer Complex disease	European Regional Development Fund (cofounded)	2015-ongoing	(Cocca et al., 2020) [33]
7	Germany[German genome project (genomeDE)]	Population database Cancer Rare disease	The European Commission under the structural reform programme (GD REFORM), Federal Ministry of Health (BMG)	2019-ongoing	(Onstwedder et al., 2022) [34]
8	Poland[Genomic map of Poland]	Reference genome	European Centre of Bioinformatics and Genomics	2014–2020	(Kaja et al., 2022) [35]
9	Belgium [Belgian Genome Biobank (BGB)]	population database	the Research Foundation Flanders (FWO)	2022-ongoing	https://www.elixir-belgium.org/projects/belgian-genome-biobank
10	The Netherlands [Genome of the Netherlands]	Rare disease (trio design)	Netherlands Organization for Scientific Research	2009-ongoing	(Boomsma et al., 2014) [36]
11	Czech Republic [Czech Genomes for Theranostics]	Population database	The A-C-G-T project	2019–2023	https://www.acgt.cz/en/
12	Greece [Genome of Greece]	Population database Monogenic disease Multifactorial disease	Crowdfunding and private donations	2010-ongoing	(Patrinos et al., 2020) [37]
13	Faroe Islands [Faroe Genome project (FarGen)]	FarGen infrastructure Faroese reference genome	DKK on the Faroese national budget Danish Parliament The Faroese Health Authority	2016-ongoing	(Mortensen et al., 2023) [38]
14	Denmark [Danish National genome project]	Population database	Novo Nordisk Foundation	2017- ongoing	(Khoury et al., 2022) [39]
15	Finland[FinnGen]	Population database (500,000 participants) Pharmacogenomics	Business Finland and international pharmaceutical companies AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Genentech, part of Roche Group, GSK, Janssen, Maze Therapeutics, MSD, Novartis, Pfizer, Sanofi.	2017-ongoing	https://www.finngen.fi/en/node/17#
16	Estonia[Estonia genome project]	Population database Biobank Pharmacogenomics	the Estonian government and the ERDF	2000-ongoing	(Metspalu, 2004) [40]
17	Scotland[The Scottish genome partnership]	Population database Cancer Rare disease	Scotland’s Chief Scientist Office. UK’s Medical Research Council	2016–2020	https://www.scottishgenomespartnership.org/
18	Switzerlands [Swiss Personalized Health Network] [Pan-Cancer Analysis of Whole Genomes Project (PCAWG)]	Population database Cancer	The Swiss Academy of Medical Sciences (SAMS)	2017- ongoing	https://sphn.ch/ https://frontlinegenomics.com/world-of-genomics-switzerland/
19	Wales[Welsh Genomics for Precision Medicine]	Precision medicine	Government funding	2017-ongoing	https://www.gov.wales/written-statement-genomics-precision-medicine-strategy
20	North Ireland [Northern Ireland Genome project]	Rare disease	UK Medical Research Council	2015- ongoing	https://frontlinegenomics.com/world-of-genomics-northern-ireland/
21	Hungary [Hungary genome project]	Rare disease Cancer	Government funding	2015-ongoing	https://international.pte.hu/news/launch-hungarian-national-genome-programme-has-been-initiated
22	Austria[Genome Austria]	Population database Rare disease Cancer	Austrian Federal Ministry for Education, Science and Culture	2016-ongoing	https://www.eurekalert.org/
23	Portugal [Genome PT)	Reference genome	European Union financial support National/regional public financial support	2017–2020	https://www.genomept.pt/copia-support
24	Malta[Malta human genome project]	Reference database genetic disorders	Malta Council for Science and Technology (MCST) R&I2013-041.	2016–2017	(Borg, 2018) [41]
25	Turkey[Turkish genome project]	Population database Common diseases Rare disease	ADOPT BBMRI-ERIC, European Union’s Horizon	2017-ongoing	(Özçelik, 2017) [42]
26	Cyprus[The Cyprus Human Genome Project]	Rare disease Common diseases	European Commission, Republic of Cyprus, University of Cyprus	2019–2026	https://biobank.cy/cy-biobank-2/
Asia
27	Japan[Japan genomic medicine program]	Reference genome Rare disease	Japan Agency for Medical Research and Development (AMED)	Launched 2015	(Furusawa et al., 2019) [43]
28	China[China Precision Medicine Initiative]	Population database 100 million human genomes by 2030	The Ministry of Science and Technology The Chinese Academy of Sciences	2017- 2016–2030	(Wang et al., 2023) [44] (Causio et al., 2022) [45]
29	Russia [The genome Russia project]	Population database	Russian Academy of Sciences and the Ministry of education and Science	2014-ongoing	(Oleksyk et al., 2015) [46]
30	Qatar [Qatar genome project]	Population database Common disease Pharmacogenomics	Supported by the Sidra Medical and Research Center, Qatar Ministry of Health	2015-ongoing	(Thareja et al., 2021) [47]
31	United Arab Emirates[The Emirati Genome Program]	Population database Rare disease Common disease	Governmental funding	2019-onoing	(El Naofal et al., 2023) [48]
32	Saudi Arabia [The Saudi Human Genome Program]	Rare disease Cancer	King Abdulaziz City for Science and Technology (KACST)	2013-ongoing	(Alrefaei et al., 2022) [49]
33	Korea[Korean genome project]	Reference database	Genome Research Foundation, Ulsan National Institute of Science and Technology,	2006–2021	(Jeon et al., 2021) [50]
34	Singapore[SG100K [Singapore genome variation project]	Population database Common disease	National Medical Research Council (NMRC)	2017–2027	(Wu et al., 2019) [51]
35	Thailand [Genomics Thailand]	Rare disease Cancer Pharmacogenomics Coommon disease	Health Systems Research Institute (HSRI)	2019–2023	(Sukasem et al., 2023) [52]
36	Hong Kong [Genomic Medicine in Hong Kong]	Rare disorders Cancers Hereditary disease Genome database	Hong Kong genome institute, Government funding	2021-ongoing	https://hkgp.org/en/
37	India [IndiGen Genome Project]	Population database Rare disease Precision medicine	Department of Biotechnology, Government of India	2019–2023	(Dalal et al., 2023) [53]
38	Indonesia [Indonesian Genome Diversity Project]	Population database	Indonesia's government	2022–2024	https://ega-archive.org/datasets/EGAD00001004156
39	Iran[Iranome]	Population database	Iran Vice-President Office for Science and Technology	2011–2019	(Fattahi et al., 2019) [54]
North/South America
40	United states [All of Us Research Program; Genomic working group]	Population database	National Institute of Health (NIH)	2016-ongoing	(Mapes et al., 2020) [55]
41	Brazil[Brazilian Initiative on Precision Medicine (BIPMed)]	Infrastructure Rare disease	The São Paulo Research Foundation (FAPESP)	2015-ongoing	(Rocha et al., 2020) [56]
42	Chile[1000 Genomes Chile)	Population database	Center for Genome Regulation, Center for Mathematical Modeling, Advanced Center for Chronic Diseases, the Geroscience Center for Brain Health and Metabolism, the Millennium Institute for Integrative Systems and Synthetic Biology	2018–2022	(Vidal et al., 2019) [57]
43	Cuba [Cuba’s population structure]	Population database	Government funding		(Fortes-Lima et al., 2018) [58]
44	Mexico [OriGen project]	Genome database	Mexico's CONACYT CienciaBásica Program, the International Centre for Genetic Engineering and Biotechnology (ICGEB).	2023––2026	https://tecscience.tec.mx/en/interactives/origen-project/
45	Canada [Genome Canada]	Population database Common disease Rare disease Infectious disease	The Government of Canada, Department of Innovation Science and Economic Development Canada (ISED),	2000-ongoing	(Husereau et al., 2023) [59]
46	Peru [Peruvian Genome Project]	Population database	Public funding		(Harris et al., 2018) [60]
Africa
47	Egypt [Egypt Genome Project]	Population database Common disease Rare disease Cancer Precision Medicine Ancient Egyptian DNA	Academy of Scientific Research and Technology (ASRT)/Egypt Center for Research and Regenerative Medicine (ECRRM)	2022-ongoing	(Elmonem et al., 2024) [61]
48	Nigeria [Nigerian 100 K Genome Project]	Population database Non-communicable disease	African Center for Translational Genomics (ACTG)	2020-ongoing	(Fatumo et al., 2022) [62]
49	Southern Africa[Southern African Human Genome Programme]	Genetic database	South African Medical Research Council (SAMRC), in partnership with the BGI	2011- ongoing	(Glanzmann et al., 2021) [63]
Australia
50	Australia [OurDNA]	Reference database	Australian Government	2022-ongoing	(Belcher et al., 2019) [64]

We searched for the terms “Genome project” or “Genomic project” with the names of countries recognized by the United Nations (n = 195). This was performed using different search engines: Pubmed, Google Scholar and Google.

Some of the relatively small-scale projects covering a thousand to a few thousands genomes are mainly aiming to elucidate the ancestral structure of their population and building a national reference genome or a population genomic database, such as in Poland, Chile and Cuba [35], [57], [58]. Many of such projects are already concluded. In contrast, large-scale ongoing genomic projects, such as the All of Us Research Program in the USA [55], the European '1 + Million Genomes' Initiative [65] and the Chinese Precision Medicine Initiative [44], [45], each with the target to eventually gather the sequences of millions of human genomes (both healthy and diseased) to serve the goals of precision medicine at both the national and international levels. Other countries including Egypt are aiming to incorporate their populations' genomic input into the global genomic map, so that their populations are not missed out. Furthermore, sharing genomic data across different countries and regions will definitely aid to advance global knowledge of both human health and disease.

Many of the national projects presented in Table 1 are coupling population genomics with the study of rare disease, common disease or cancer genomics; however, a few are also targeting pharmacogenomic studies as a main objective of the project, such as in Finland, Estonia, Qatar and Thailand [40], [47], [52]. A unique aim that is not declared by any other national project, apart from the Egyptian, is the study of ancient DNA as part of the genomic heritage of a certain population [61].

A few small countries are going a step further and aim to investigate the genomes of a substantial portion of their populations (>10 %), such as Finland, Iceland, Qatar and United Arab Emirates [31], [47], [48]. In contrast, due to the large population structure of Egypt, the Egypt Genome aims to sequence approximately 1 in 1,000 apparently healthy Egyptian individuals, which should be enough to build the Egyptian reference genome and a representative population variant database. The Egypt Genome further sails into the uncharted territory of genomically underrepresented populations in Africa and the Middle East. The meaningful research findings of the project are expected to fill the existing knowledge gap and provide the missing pieces of the global genomics map.

Conclusion

The strategic vision of EG is to study the genomics of the modern and ancient Egyptians and mine the genomic wealth in both. It is the first wide scale gene database for the North African region, to compensate for the defective contemplation of the African and Middle eastern populations in the current databases. With the genomics at the core of the national strategic vision, EG is predicted to generate insightful genomic knowledge; to promote the integration of genomics into clinical and research practices; and to spearhead the implementation of genomic-driven healthcare and precision medicine. EG is designed so that it can reliably study and assess the actual burden of rare diseases among the highly consanguineous Egyptian population. Other study arms include cancer, non-communicable diseases (NCDs), predisposition to various infectious diseases and pharmacogenomics. Some of these milestones have already been reached including the utilization of phenotype platforms and building the capacity to biobank, sequence and genotype at a large scale. This is expected to provide critical insights into various diseases’ etiologies, to inform potential therapeutic opportunities and to support patient-centered care model and healthcare reforms to mitigate diseases’ burden. The provided capacity building opportunities in genomics for young researchers in Egypt and Africa will be a game changer to empower genomic medicine in Africa. The impact of EG is predicted to go beyond Egypt and Africa as it fills the knowledge gaps in health and disease genomics and expand genomic-driven healthcare thus guaranteeing improved and sustainable genomic healthcare systems for better outcomes. The study of verified Ancient Egyptians human remains is a critical arm of EG aiming to unravel insightful knowledge on ancient human genome, evolution and history. Being one of the oldest nations, Egypt is the first nation to embrace the ancient ancestry DNA in its genome project to delineate the genetic bridging between its ancient and contemporary populations.

Availability of data and materials

Not applicable.

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Funding

Egypt Genome (EG) is supported by a research grant from the Academy of Scientific Research and Technology, Ministry of Higher Education and Research, Cairo, Egypt.

Compliance with ethics requirements

Not applicable.

CRediT authorship contribution statement

Khaled Amer: Conceptualization, Investigation. Neveen A. Soliman: Conceptualization, Writing – review & editing. Ahmed Moustafa: Conceptualization. Mohamed A. Elmonem: Conceptualization. May Amer: Investigation. Tarek Taha: . Mahmoud Sakr: Supervision. Khaled Abdel Ghaffar: Project administration.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Biographies

KhaledAmer https://orcid.org/0000-0001-6896-9449 Scopus Author ID: 57064012300 Khaled E. Amer is Professor of General Surgery in the Military Medical Academy and Consultant Hepato-biliary & Liver Transplant Surgeon at the International Medical Center. He has an extensive and multidisciplinary track record that spans a number of medical fields as a practicing surgeon, academic and organizational design specialist. He was tasked with the founding and establishment of Armed Forces College of Medicine (AFCM) in 2013, for which he led the institutional set up and the development of academic curricula in accordance with the highest international standards for higher education in medicine. He was tasked in 2018 with the establishment of the Egypt Center for Research and Regenerative Medicine (ECRRM), an innovative research facility including the National Reference Genome Laboratory that serves as the central genomic hub for Egypt Genome research studies. He is the principal investigator of Egypt Genome Project. Prof. Amer is a distinguished academic who regularly publishes in high-ranking peer-reviewed journals.

NeveenA.Soliman https://orcid.org/0000-0002-8942-1973 Scopus Author ID: 55212159700 Neveen A. Soliman is a Professor of Pediatrics at Kasr Al Ainy Faculty of Medicine, Cairo University. She is the founder and director of the Egyptian Group for Orphan Renal Diseases (EGORD). She is an active member of the Medical Research Council at Academy of Scientific Research and Technology and served as the Vice Dean for Postgraduate Affairs and Research of Faculty of Medicine, Cairo University. Prof. Soliman main research interest is understanding and unraveling the genetic basis of chronic kidney diseases. Her research work is primarily focused on clinical and molecular characterization of monogenic kidney diseases. She has extensive experience in the overall assessment of patients with rare and inherited kidney diseases and the application of genetic and genomic analysis. She is currently the Editor-in-Chief of the Journal of Rare Diseases, a member of several nephrology and genetics scientific societies and serves on the scientific advisory council of rare disease foundations as the Oxalosis Hyperoxaluria Foundation. She has been elected as the Chairman of the Scientific Committee of Egypt Genome Project (EGP). Prof. Soliman has authored and co-authored numerous publications many of them in high-ranking journals.

Sameh Soror https://orcid.org/0000-0001-6474-8884 Scopus Author ID: 16837604900 Sameh Soror obtained his PhD degree in genetics from Kaiserslautern University, Germany in 2007. He was a postdoctoral fellow 2008-2012 at free university Brussels and flams institute for biotechnology, Belgium. When he returned home, he has established Helwan University center of scientific excellence for structural biology research and led the center research activities. In 2018 he was appointed as supervisor of scientific and cultural relations sector at the Academy of Scientific Research and Technology (ASRT), and he participated in drafting the initial plan of the Egyptian genome project. Since 2021 he is a member of Egypt Genome project Scientific Committee.

YehiaZ. Gad https://orcid.org/0000-0002-8432-4541 Scopus Author ID: 6603409200 Yehia Z. Gad has graduated from the Faculty of Medicine, Cairo University in 1979. He got M.Sc. and M.D. degrees in Pediatrics from the same Faculty in 1983 and 1992, respectively. He started his research career as a fellow in Human Genetics Dept., National Research Centre (NRC) in 1981 then was promoted along the years up to the post of Professor of Molecular Genetics in 2003. He is a fellow of Johns Hopkins University and Albert Einstein College of Medicine, USA. He published 39 articles in national and international journals in the fields of molecular genetics, genomics, endocrinology and paleobiology. He is currently an Emeritus Prof in the NRC and the Scientific Supervisor of the ancient DNA lab at the National Museum of Egyptian Civilization.

AhmedMoustafa https://orcid.org/0000-0002-0111-3555 Scopus Author ID: 55251149600 Ahmed Moustafa is a bioinformatics expert specializing in systems genomics. He earned his B.Sc. in computer science from Alexandria University and his Ph.D. in computational genetics from the University of Iowa, furthering his studies with a postdoctoral fellowship at the J. Craig Venter Institute (JCVI). Then, Dr. Moustafa became a bioinformatics faculty member at the American University in Cairo (AUC), serving in leadership roles in the Biology Department and the Biotechnology Graduate Program. He remains affiliated with JCVI as an adjunct scientist and currently spearheads the bioinformatics department at the Egypt Center for Research and Regenerative Medicine (ECRRM). An elected member of the national Egyptian Genome Project scientific committee and a fellow of the African Academy of Sciences, Dr. Moustafa's extensive research encompasses environmental microbial genomics, human genomics, and the microbiome.

MohamedAbd Elmonem https://orcid.org/0000-0002-3154-1948 Scopus Author ID:55921282400 Mohamed Abd Elmonem is a Professor of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, Egypt. He graduated from medical school in December 2000 and obtained his Master and Medical Doctorate degrees in Clinical and Chemical Pathology from Cairo University, Egypt in 2006 and 2012, respectively. He obtained a second PhD in Mechanisms of Human Disease from University Hospital Leuven, KU Leuven, Belgium in 2018. He is currently the head of the inherited metabolic disease laboratory at Cairo University Children's Hospital and a senior member at the Clinical Genomics team in the newly launched Egypt Genome Project. His research interests include elucidating the genetic and pathogenic backgrounds of various inherited genetic disorders and the discovery of novel biomarkers for such disorders.

MayAmer https://orcid.org/0000- Scopus Author ID: May Amer is a Genomics Researcher in the Egypt Center for Research and Regenerative Medicine (ECRRM). She is part of the founding team in Egypt Genome Project. She obtained her M.Sc in Molecular Medicine from Charité - Universitätsmedizin Berlin in Germany, focusing on the role of CPT2 in early angiogenesis and allo-activation, associated with acute GVHD. Thereby studying the influence of endothelium-specific CPT2 deletion on endothelial function under in vitro allo-activation mimicking GVHD. Prior to that, she worked as a Research Associate as part of the Tumour Biology team at the Children Cancer Hospital Egypt 57357, working on protein misfolding in paediatric brain tumours, particularly the activation of the Unfolded Protein Response (UPR) in brain tumour cells during stress, and its link to protein misfolding and aggresome formation. Additionally, she has worked on two projects in the Charité research teams. The first studied the functional characterisation of transient receptor potential (TRP) channels in malignant eye tumour cells. The second was to elucidate the role of RNA binding for TRIM2 and TRIM3 function in NIL-induced motor neurons.

Ameera Ragheb https://orcid.org/0000-0002-2529-272X Scopus Author ID: Ameera Ragheb graduated from University of North Texas with a B.S. in Cytotechnology and became an ASCP certified cytotechnologist in 2009, at the Mayo School of Health Sciences. After gaining more than ten years of work-experience in the USA, among which is the establishment of the cytology department in Inform Diagnostic (formerly known as Miraca L.S), Ameera joined Egypt Center for Research and Regenerative Medicine (ECRRM) team, as Egypt Genome Project coordinator (in 2020).

AmiraKotb https://orcid.org/0000-0002-0960-8202 Scopus Author ID: Amira Kotb is Lecturer of Clinical and Chemical pathology, Kasr Al Ainy Hospital, Cairo University, Egypt. Clinical Geneticist and Researcher, Clinical Genomics department, ECRRM. She has attained her M.D. at Faculty of Medicine, Cairo University, Egypt, in November 2019. Her professional interest is in clinical and molecular genetics. She practiced both Sanger and next generation sequencing, variant analysis, interpretation and classification as part of her Master degree and MD, as well as her subsequent contribution to different hereditary disease projects. She is currently part of the Clinical Genomics team; ECRRM, working on the genetic analysis and interpretation of the genetic variations in Egypt Genome project.

TarekTaha https://orcid.org/0000-0001-6156-1213 Scopus Author ID: 57204479386 Tarek Taha is currently the Head of the Stem Cell and Regenerative Medicine branch in Egypt Center for Research and Regenerative Medicine (ECRRM), member of the scientific committee of Egypt Genome Project, Consultant, and head of the immunology and Tissue Typing department in the Egyptian Armed Forces Central Lab (Former). Also, He is the Founder of the immunogenetics unit in the armed forces central lab (2017), his contribution in this review article is by collecting data about Genome Projects in different countries, establishing the objectives, outcomes, and impact of EGP on enhancing Egyptian health.

WaelAli https://orcid.org/0000-0001-5998-9106 Scopus Author ID: 57218318110 Wael Ali is a graduate of the School of Medicine, Cairo University (1996), and obtained his Master Degrees in Clinical and Chemical Pathology, from Ain Shams University, in addition to his master degrees in Hospital Management (AAST) and Health Economics (Cairo University). As a Google certified Project Manager and PMP holder, he had previously served as a manager of Laboratories, in different facilities, such as, Biological Prevention Laboratory at Central Laboratories of Chemical Warfare Department (2011-2017), which was the first laboratory to run NGS technology in Egypt. Since 2019, he is the Director of Central Laboratories at Egypt Center for Research and Regenerative Medicine (ECRRM), which is the executive sector of Egypt Genome Project, as one of its main ongoing projects.

MahmoudSakr has over 15 years of experience in high-level science, technology, and innovation management. He was the dean of the Genetic Engineering and Biotechnology Institute, the co-founder of the Center of Scientific Excellence for Advanced Sciences at Egypt's National Research Center (NRC), and the Vice President of SESAME, NAM, and Egypt's Plenipotentiary in JINR. Sakr has over 130 scientific publications to his name, has co-authored books, and has mentored 35 master's and Ph.D. students in the field of biotechnology. He was the founder and initiator of numerous entities and National RDI projects, including the Reference Egyptian and Ancient Egyptian Genome Project, the National Program of Technological Incubators, the Egyptian STI Observatory, Knowledge and Technological Alliances, the Egyptian Innovation Bank, and the ASRT Company for Technology Transfer. He actively took part in the establishment of the first solar energy lab in South Egypt (Suhag), known as the “Egyptian-Chinese Joint Laboratory for Renewable Energy,” in collaboration with China. He received the State Encouragement Award in science and technology as well as the National Research Council Award for scientific excellence in biotechnology.

Khaled Abdel-Ghaffar https://orcid.org/0000-0001-5340-789X Scopus Author ID:6507541437 Khaled Abdel-Ghaffar currently serves as Egypt's Minister of Health and Population. He is a prominent figure in dentistry with a career spanning 4 decades. He previously held the position of Minister of Higher Education and Scientific Research for 6 years. As a professor at Ain-Shams University, specializing in Oral Medicine, Oral Diagnosis, Oral Radiology, and Periodontology, Prof. AbdelGhaffar has significantly advanced dental research and practices globally. His extensive body of work includes numerous publications in international peer-reviewed journals, earning him multiple national and international awards in recognition of his contributions to Dentistry. Throughout his career, Prof. AbdelGhaffar occupied several roles, including Clinical Professor at the Medical College of Georgia and Visiting Professor at the University of Texas. He additionally assumed responsibilities as the Vice President for Postgraduate Studies and Research and Dean of the Faculty of Dentistry at Ain-Shams University. His achievements led to widespread acclaim and recognition. Prof. AbdelGhaffar obtained a PhD in Dental Surgery from the University of Texas after completing his studies at Cairo University’s Faculty of Oral and Dental Medicine. He was awarded honorary Doctorate from the University of Hiroshima and an honorary Fellowship from the Royal College of Physicians and Surgeons of Glasgow in 2019.