World of Genomics: Morocco

The Kingdom of Morocco, bordering the Sahara Desert and the strait of Gibraltar, is best known for its mountain ranges, wild beaches, fragrant cuisine and beautiful cities such as Casablanca, Marrakech and Rabat. Morocco has a rich heritage and unique culture and is home to the world’s first-ever university, the University of Al-Qarawiyin. Morocco continues to be a hub for science and technology and in this World of Genomics piece, we will review Morocco’s novel genomics research across a wide spectrum of diseases and applications such as cancer and COVID-19.

The population of Morocco

The Kingdom of Morocco is in the western part of North Africa, bordering the Mediterranean Sea, Algeria, the Sahara Desert and the Atlantic Ocean. Arabic is the official language, but Berber dialects (the language of the Amazigh people) and French are also widely spoken.

Morocco has been home to the Berbers since 2000BCE. Arabs invaded around 685CE, bringing with them Islam, which is now the state religion. In 1912, France gained a protectorate over Morocco, de-facto controlling the region. This lead to many years of civil unrest and uprisings until Morocco finally gained independence from France in 1956. After gradual political reforms, Morocco established a constitutional monarchy, with Aziz Akhannouch as the current prime minister and King Mohammed the VI as the current head of state.

Geographic and demographic information

Summary statistics

• Land area: 446,300 km²
• Gross domestic product (GDP):
  • Total: 2021 estimate: 132.73 billion USD
  • Per capita: 3,496.8 USD

Population statistics

• Population size: 2021 estimated.: 37,344,787 (growth rate: .91%)
• Birth rate: 2020 estimated: 18.5 per 1000 people
• Death rate: 2020 estimated: 5.1 per 1000 people
• Infant mortality rate: 2020 estimated: 18.3 per 1000 people
• Life expectancy: 2020 estimated: 77 years.
• Ethnicities: Arab (44%), Arabized Amazigh (Berber) (24%), Other Amazigh (21%), Mauritanian Moors (10%), Other (1%)
• Religions: Sunni Muslim (98%), Shia Muslim (1%), Christian, Jewish and Baha’i (1%)

Healthcare and Health Priorities in Morocco

A general overview of the Moroccan Healthcare System

When Morocco gained independence in 1956, there were only 400 private practitioners and 300 health physicians in the entire country. In 1959, the first health care policy was implemented, providing free healthcare services to the public. By 1992, healthcare was available to over 70% of the population through state-funded programs and administration. In 2005, Morocco introduced AMO (Assurance Maladie Obligatorie), a mandatory and contributory health insurance scheme. In 2011, the constitution of Morocco was amended to recognise the right to healthcare.

The Moroccan healthcare system comprises both public and private sectors. Despite increases to the healthcare budget, investment in the public healthcare sector is still relatively low, consisting of less than 6% of GDP ($1.63 billion) and out-of-pocket expenses remain high. Out-of-pocket expenses remain the primary source of funding for around 46% of the population and are a significant barrier to accessing healthcare. Moreover, patient dissatisfaction with the public health system remains widespread, with residents citing problems with the quality of care and lack of access to health services and facilities, particularly in rural areas. Over half of the rural population do not have access to healthcare facilities and many do not have access to safe drinking water. Morocco is ranked 108^th in the Global Health Security Index, but first in North Africa.

In 2012, the RAMED program (Le Régime d’Assistance Médicale) was ramped up to establish universal healthcare coverage through nonsubsidised and subsidised social health insurance. An additional 8.5 million people were given access to publicly funded healthcare. In 2014, reforms to medicine pricing lowered the cost of treatment and brought a reduction in the prices of more than 1,400 medicines on the market. Ongoing projects include a $1.1 billion project to build 29 new hospitals, $440 million will be invested to build regional and provincial hospital centres and $72.7 million will be invested in upgrading and extending existing healthcare facilities and hospitals. Funding from external sources only contribute to 1.1% of the health budget in Morocco.

Major health problems facing Morocco

Morocco has seen significant improvements (75%) in reducing maternal mortality and infant mortality, thanks to efforts by the United Nations Population Fund (UNFPA), United Nations International Children’s Emergency Fund (UNICEF) and contributions from the Spanish government. In 2012 the Ministry of Health created the maternal mortality surveillance system and The World Health Organisation, UNFPA and UNICEF are working alongside the Moroccan Ministry of Health to develop a maternal and child health strategic action plan. However, the strict nature of abortion laws in Morocco and the absence of genetic screening services may prove to be significant hurdles in curtailing maternal and infant mortality rates.

Morocco is seeing an increase in deaths from non-communicable diseases, which now account for 75% of all deaths. Cancer, diabetes and cardiovascular disease make up 40% of the major causes of death. Cancer is responsible for 13.4% of deaths in Morocco, with 50,000 new cases each year. The Lalla Salma Foundation for Cancer Prevention and Treatment, is working alongside the Ministry of Health to expand access to cancer screening. Morocco is the first African country to join the board of the International Agency for Research on Cancer. Moreover, Morocco launched a breast and cervical cancer screening program in 2010, which was scaled up in 2017 to give access to breast cancer screening in all 12 regions of the country. Morocco also recently launched a National Plan for Prevention and Treatment of Cancer, a strategic action plan for 2020-2029.

Infectious diseases still account for 18% of deaths, but immunization and disease control programmes have put an end to deaths from malaria, polio, trachoma and schistosomiasis. However, tuberculosis (TB) remains endemic, despite freely available treatment and considerable public health efforts. A particularly concerning development has been the increase in deaths due to multi-drug resistant TB. However, there is hope on the horizon, Morocco has recently launched a Tuberculosis Prevention Campaign, with an aim of eliminating TB by 2030. Moreover, researchers from the Moroccan Foundation for Advanced Science, Innovation and Research have developed the first 100% Moroccan TB Diagnostic Test, a mobile device that can deliver results in just 30 minutes.

Morocco’s COVID-19 response

Morocco had prior knowledge of managing epidemics due to its past experiences with Ebola, MERS-CoV and influenza. Well-trained rapid response teams were already present in the country and existing infrastructure to support patient care helped in their early response to the pandemic. Morocco already had a significant body of legislation to manage health crises and there was already investment in maintaining essential services. However, due to strains on human resources and delays in communicating the results of diagnostic tests, there was a high mortality rate in patients admitted to the ICU. The conditions of public hospitals and the quality of patient care came under intense scrutiny and criticism. As of the date of publication, there have been 1.26 million cases, with 16,237 deaths.

Genomic Medicine Capabilities

Existing genomic medicine services

There is no systematic screening of specific genetic diseases in Morocco and there is no newborn screening. According to international projections, the number of newborns with a genetic condition in Morocco is estimated to be 5%. There are also no regulations or laws around the practice of genetics and genetic testing and in 2014 the Moroccan Ministry of Health presented in a press release its intention to ban the free sale of DNA and paternity tests. There is no formal infrastructure or national program for genetic counselling in Morocco outside of very specialised departments at university hospitals.

Cancer genomics research

Dr. Sayeh Ezzikouri of the Pasteur Institute of Morocco has been a leading researcher investigating genetic signatures of viruses associated with cancer. The eight major carcinogenic viruses; human papillomaviruses (HPV), hepatitis B and C viruses, Epstein-Barr virus (EBV), human T-Cell Lymphotropic Virus Type 1 (HTLV-1), Human herpesvirus 8 (HHV-8), Merkel cell polyomavirus and human immunodeficiency virus-1 (HIV1), may be responsible for over 14,000 malignancies per year in Morocco alone. Genetic and epigenetic variations may modulate individual susceptibility to developing cancer as not all individuals infected with these viruses develop cancer and host genetic signatures may be potential biomarkers for early cancer detection.

Dr. Ahmed Belmouden and Nadia El Kadmiri of the Laboratory of Cell Biology and Molecular Genetics, Ibn Zohr University, have identified several genomic, transcriptomic, inflammatory and virulence markers in Helicobacter pylori-associated Gastric Cancer. H.pylori infection has been implicated in inducing DNA methylation at several different loci in gastric epithelial cells. These epigenetic markers could prove to be biomarkers for early detection and prevention of gastric cancer.

Dr. Mohammed El Mzibri of the National Center for Energy, Sciences and Nuclear Techniques investigated telomerase activity in the context of bladder cancer, using genomic and epigenomic profiling to investigate “hotspot mutations” and DNA methylation of the TERT promoter. While also identifying biomarkers for improved diagnosis, this study also revealed telomerase crosstalk is mediated by miRNA-138, which may potentially be therapeutically targeted in situ.

Dr. Rachid El Fatimy of Mohammed VI Polytechnic investigated RNA therapeutics for the treatment of human brain cancer. Glioma commonly activates miRNA-10b, which goes on to promote tumour growth. In this study, the mechanism by which miRNA-10b activation occurs is elucidated and knockdown studies of long non-coding RNAs (lncRNA) regulate gene expression at epigenetic, transcriptional and translational levels, leading to glioma cell death. Identifying these specific enhancer and promoter RNAs provides a new potential therapeutic target for the treatment of glioma.

Infectious disease genomics research

Researchers from the Laboratoire d’Immunologie Clinique contributed to a major global genomics study that identified the prevalence of autoantibodies neutralizing type 1 interferons in around 20% of all fatal COVID-19 cases, helping to further our understanding of why COVID-19 has such a wide spectrum of clinical symptoms.

Dr. Abdelhamid Barakat of the Pasteur Institute has done extensive genomics research on inherited diseases, including retinal dystrophies, optic neuropathy, congenital myasthenic syndromes and hereditary deafness. Using computational screening, he has recently identified the neuropilin-1 receptor (NRP-1) as a potential therapeutic target for the treatment of COVID-19. Using a library of 1167 compounds previously used in COVID-19 studies, he found five molecules which interact with key NRP-1 receptor residues, which could be promising drugs for further biological assays to investigate their potential as anti-viral drugs for the treatment of COVID-19.

Notable projects

• The African Genome Centre, a hub for next-generation sequencing, and the largest high-performance computing cluster in Africa is based at Mohammed VI Polytechnic University:
  • Leveraging these resources, researchers integrated multi-omics and protein-protein interactomes to investigate markers for the diagnosis and prognosis of colorectal cancer.
  • They identified 15 markers that revealed several hub genes that may have a significant role in colorectal cancer and these 15 markers displayed over a 98% accuracy in detecting colorectal cancer in patients.
  • They also explored machine-learning approaches for the prediction of RNA modification sites and investigated the use of computational algorithms such as the Monte Carlo Method for drug discovery for the treatment of hepatitis C.
• The Moroccan Genetic Disease Database (MGDD) aims to act as a database of “DNA variations related to inherited disorders and disease susceptibility.”
• Dr. Bellaoui Mohammed of Mohammed First University launched the BRO biobank ( the first biobank in Morocco) in November 2015. This biobank includes Moroccan and North African ethnic groups in international biomedical studies, which will be critical in reducing the disparities in healthcare and ensuring previously underrepresented groups can benefit from advances in research and treatment.
• “MoHuMuda” (Moroccan Human Mutation Database), the first Moroccan database collecting genetic diseases and mutations identified in the Moroccan population.

Notable organisations and companies

• Moroccan Foundation for Advanced Science, Innovation and Research (MAScIR): A non-profit related to Mohammed VI Polytechnic University that aims to “promote and develop technological research centers in the fields of materials and nanomaterials, biotechnology, microelectronics and life sciences.”
• In Morocco, genomics and human genetics research and resources are sporadic and carried out by individuals in disparate universities and institutions. Consequently, the Moroccan Society of Genomics and Human Genetics (Sociètè Marocaine de Gènomique et Gènètique Humaine (SM2GH)) was created in 2018 to promote collaboration and highlight genomics research in Morocco.
• The Human Molecular Genetics Unit at Morocco Pasteur Institute: This lab has been a leader in documenting mutations and polymorphisms reported in Moroccan population, and developed The Moroccan Genetic Disease Database (MGDD)

Notable individuals

• Dr. Abdel Aziz Sefiani: The first medical geneticist in Morocco and pioneer of genomics research, is head of the Department of Medical Genetics in Rabat.
• Dr. Siham Chafai Elalaoui: Assistant Professor of Genetics at the Faculty of Medicine and Pharmacy of Rabat, managed the update of MoDyDa (Moroccan Dysmorphology Database), part of the Moroccan committee responsible for coordinating the internation MedGenMed project with the European Genetic Foundation, member of the committee of the Orphanet Project, and member of MoHuMuda committee
• Dr. Sayeh Ezzikouri: Board member of the World Society for Virology, head of the viral hepatitis laboratory of the Pasteur Institute Morocco and national committee member on the national strategic plan to tackle hepatitis
• Dr. Abdelaziz Sefiani: President of the Society of Moroccan Society of Medical Genetics
• Nadia El Kadmiri: Founder and president of the Moroccan Association for Research and Ethics.

Future genomics landscape

New research genetic centres are emerging in Morocco. For example, the partnership between The Rabat Abulcasis Health Sciences International University (UIASS) and Paris (Imagine) Institute of Genetic Diseases, that are working together to further genomic research and medicine. Another example includes the creation of the laboratory of genetic engineering at the Euromed University of Fez, which is being developed under a partnership between Dassault systems and the Ministry of Higher Education.

Despite the lack of a formal genetic counselling program, services are being set up at specialised departments at university hospitals. Dr. Siham Chafai Elalaoui runs a genetic counselling service at the National Institute of Health in Rabat, and Dr. Sabdelaziz Sefiani recently used Next Generation Sequencing (NGS) techniques to provide genetic counselling for families at risk of cystinosis. These initiatives are helping to advance genomic medicine capabilities.

Moroccan universities including the Pasteur Institute are also working to help develop the African Genomics Medicine Portal, which will function as a dedicated resource to access information on genomics specific to Africa. Other projects such as The African Genome Variation Project , MoHuMuDa, and partnerships with Orphanet are also helping to realise the capabilities and applications of genomic medicine and research in Morocco.

References

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• https://bioinformatics.um6p.ma/#about
• Population and demographic statistics: World Bank

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