SCIENCE AND HEALTH IN THE MEDITERRANEAN COUNTRIES : genes, pathogens and the environment

Accademia Nazionale dei Lincei, Rome

12 – 14 October 2009



AUTHOR(S):Nejat Akar, MD, Prof.

INSTITUTION(S) :Pediatric Molecular Genetics Department of Ankara University, Turkey

TITLE OF TALK :Familial Mediterranean fever in Mediterranean Area : where are we now ?


ABSTRACT (max. 300 words, including references) :

Familial Mediterranean fever (FMF) is an autosomal recessive inherited disease caused by mutations in MEFV gene. This disease is characterized by recurrent episodes of fever accompanied with topical signs of inflammation. It is mostly frequent in Mediterranean populations including Arabs, Jews, Turks and Armenians. The deadly complication of the disease is Renal amyloidosis. There are several FMF case reports from the surrounding countries of Mediterranean Sea. However frequency of the carriers were reported only from some countries, highest in Israel and Turkey, lowest in Greece and Italy changing from 0.2 to 0.01 respectively. Also there are reports from Egypt, Tunis, Lebanon, North and South Cyprus. Over 80 mutations have been identified in the gene (MEFV) responsible for the disease. The most frequent mutations are M694V (40%) ; V726A (10%), M680I (10%), E148Q (3 %), M694I (3%) and unidentified mutations approximately 30%. Although common mutations among the population studied varies, MEFV mutation analysis also were reported from the above mentioned countries, commenest mutation to be M694V. There are still controversies among clinical data and existing mutations.
Most important and fatal complication of FMF is amyloidosis which is prevelant among Turks and Armenians indicating that environment may have an effect on the occurrence and also can be prevented by colchisine therapy. There are still questions to be answered for the occurrence and pathophysiology of the FMF related amyloidosis :

  1. Is it under genetic control ?
  2. which environmental factor/s have an effect ? an unknown factor ?
  3. does all the factors have a combined effect ?
  4. Mutations, Polymorphisms, other genetic elements and/or a spesific haplotype.

Although FMF is extensively studied during the last decade, there are still questions to be searched and answered.

  • There are still undiagnosed patients
  • There are still patients without necessary response for colchisine. (New therapeutic trends for FMF and also for amyloidosis).
  • Diseases That May Be Associated With FMF.
  • Famial amyloidosis is an important feature, pathogenesis should be studied
  • One mutation carrying FMF patients.
  • Intrafamilial interindividual clinical diversity
  • Polymorphisms as a possible cause of the disease (R202Q ; promotor mutations, 5’ mutations)
  • Modifier gene alterations. (MICA gene, SAA and others)

Other than the above mentioned research areas, there are still Mediterranean countries without mutation data and data on the frequency of the carriers. After a decade of research on MEFV gene, advice to the clinician for the treatment of the FMF patients is “FMF is diagnosed clinically and colchicine therapy is started immediately, whether or not mutation analysis will or will not verify the diagnosis.”


AUTHOR(S):Jean-François Bach

INSTITUTION(S) :Académie des sciences, Paris, France

TITLE OF TALK :Genes and environment : the example of immune disorders


ABSTRACT (max. 300 words, including references) :

Gene expression is conditioned by environmental factors that include factors common to all the society (e.g. physical and chemical factors such as pollution) and more personal factors (including education and behavior).
The study of discordances between monozygotic twins is particularly interesting in this regard. As an example, the question of the causes of cancer will be discussed. What is the percentage of cancers favored by environment ? What is the place left beyond genetic and environmental factors to chance and random mutations ? Is there a role for epigenetics and if so, is it dependent on environment ?
The second question is related to autoimmune and allergic diseases.
Western countries are being confronted with a disturbing increase in the incidence of most immune disorders, including autoimmune and allergic diseases. Converging epidemiological evidence indicates that this increase is linked to improvement of the socio-economic level of these countries. Epidemiological and clinical data support the hygiene hypothesis according to which the decrease of infections observed over the last three decades is the main cause of the incessant increase in immune disorders.
Independently of the need for confirmation by epidemiological prospective studies, the hygiene hypothesis still poses numerous questions concerning the nature of protective infectious agents, the timing of their involvement with regard to the natural history of immune diseases and, most importantly, the mechanisms of protection.
Three orders of mechanisms are being explored. Antigenic competition is the first hypothesis (immune responses against pathogens compete with autoimmune and allergic responses). Its discussion in the context of homeostatic regulation of lymphocyte pools has shed new light on this hypothesis. Infectious agents may also intervene through components which are not recognized as antigens but bind to specific receptors on cells of the immune system. Major attention has recently been drawn to Toll receptors and TIM proteins present on Th cells, which may express the function of the virus receptor. Another hypothesis deals with immunoregulation. Infectious agents stimulate a large variety of regulatory T cells (Th2, CD25+, Tr1, NKT…) whose effects extend to other specificities than those which triggered their differentiation (bystander suppression).


AUTHOR(S):Marc Bartoli, Nicolas Wein, Martin Krahn and Nicolas Levy

INSTITUTION(S) :Faculté de Médecine de Marseille, INSERM UMR _S 910”Génétique Médicale et Focntionelle”, Marseille, France

TITLE OF TALK :From patients diagnosis to therapeutic strategies


ABSTRACT (max. 300 words, including references) :

Dysferlinopathies are autosomal recessive diseases covering a wide spectrum of phenotypes, mainly Limb Girdle Muscular Dystrophy type 2B and Miyoshi myopathy. Onset is usually in the second decade of life, with a progressive course of muscle weakness and possible wheelchair dependency after decades of disease progression. Dysferlinopathies are caused by mutations in the large-sized gene encoding dysferlin (DYSF ; MIM# 603009, 2p13, GenBank NM_003494.2) a 237kDa plasma membrane protein which plays a central role in sarcolemmal repair.
Particular mutational data obtained from patients are valuable information regarding possible therapeutic approaches. We have shown last year that a mini-dysferlin molecule, identified in a patient with a moderately severe phenotype of dysferlinopathy, was functional for membrane repair when transferred by AAV vectors into muscle. Our findings constitute a “natural” proof of concept, and a prerequisite for therapeutic strategies for a subset of primary dysferlinopathies. We are now further developing this strategy, by testing additional constructs comprising more C2 domains to allow for “physiological” interactions between the mini-dysferlin and known partner proteins.
Exon skipping constitutes another promising therapeutic approach. Interestingly, Sinnreich and colleagues reported in 2006 a patient with an in-frame deletion of exon 32, with a very moderate phenotype ; we consider this latter observation as another “natural” proof of concept for an exon-skipping approach in dysferlinopathies. In our cohort, several patients have been identified with a premature termination codon in exon 32. After selection by bioinformatics analysis of the best targets that will induce exon skipping, we transfected oligonucleotides in myotubes trans-differentiated from fibroblasts. After 48 hours, we have shown by RT-PCR the skipping of exon 32. We then constructed lentiviral vectors enabling skipping of exon 32. Again skipping of exon 32 was observed. We are currently trying to improve the efficiency of the exon skipping and collecting cells from patients.


AUTHOR(S):Pierluigi Benedetti Panici MD ; Filippo Bellati MD ; Francesco Plotti MD ; Violante Di Donato MD ; Angela Musella MD

INSTITUTION(S) :Division of Gynecologic Oncology – University of Rome « Sapienza »

TITLE OF TALK :Evolution of cervical cancer treatment


ABSTRACT (max. 300 words, including references) :

Cervical cancer ranks as the second most frequent cancer in women worldwide. The introduction of largely applied screening programs has noticeably reduced the incidence of this cancer in developed countries, but even so most patients worldwide are still diagnosed at advanced stage of disease. Cervical cancer treatment has undergone continue evolution in order to obtain the highest therapeutic results and minimize long term morbidities. Neoadjuvant chemotherapy followed by radical surgery or radiation therapy has been proposed since the beginning of the eighties. It represents the alternative to concurrent chemo-radiotherapy in patients affected by locally advanced disease. Different combination regimens that include cisplatin appear reasonable options in a neoadjuvant setting. Unfortunately, the scarce literature dedicated to very advanced tumors does not allow drawing scientifically based specific guidelines. From data published until now, two important consideration can be made : firstly, the results of a meta-analysis carried out on randomized trial on neoadjuvant chemotherapy followed by radiotherapy showed a beneficial effect of neoadjuvant chemotherapy followed by radiotherapy of short and intense regimens. This observation is of particular importance when considering patients at high risk of not being amenable of surgery even after having completed neoadjuvant chemotherapy. The second consideration is that NACT followed by radical surgery (RS) is superior to radiotherapy. Currently no “gold standard” treatment is present in the literature, cisplatin in association with paclitaxel, ifosfamide and paclitaxel or topotecan all appear reasonable choices. Modulation of radicality of hysterectomy is a relatively recent concept emerged by the need of improving long term QoL while preserving optimal survival outcomes. Modified (type II) or classical radical (type III) hysterectomy may be performed also in patients with locally advanced disease (FIGO stage IB2–IIIB) who have shown a clinical response to neoadjuvant treatment. About lymphadenectomy, the absence of definitive evidence of survival advantage given by extensive procedure in all cervical cancer cases indicates a further insight in the clinical role of nodal resection that should be properly tailored and performed on the objective risk of node metastasis. Future research achieves have the final goal to remove only pre-operatively detected metastatic nodes.


AUTHOR(S):Ilaria Capua, Giovanni Cattoli and Calogero Terregino

INSTITUTION(S) :International Reference Laboratory for Avian influenza, Istituto Zooprofilattico Sperimentale delle VenezieViale dell’Università 10 – 35020 Legnaro (PD, Italy

TITLE OF TALK :Zoonotic and pandemic influenza in the globalised environment


ABSTRACT (max. 300 words, including references) :

The ongoing animal and human health crises caused by influenza A viruses originating from the animal reservoir has polarised attention of international organisations and donors on the need for improved veterinary infrastructure in developing countries and on the need for improved communication between the human and animal health sectors. Significant investments in capacity building have resulted in the development of diagnostic laboratories and in the improvement of scientific know-how in the field of diagnostic virology. It is known that the animal reservoir is the source of the majority of emerging pathogens which threaten global public health and also that most emerging pathogens originate (or cross the species barrier) in developing countries. It would therefore seem reasonable for the international community to capitalise on the investments that have been made as a result of the H5N1 avian influenza emergency and expand the areas of diagnostic competence, possibly on a regional basis, to set up early warning systems and improved response capacities to manage diseases of public health relevance.
Possibly the biggest challenge we have is to find novel ways to maximise the use of the information which is generated as a result of the improved networking and diagnostic capacities. In the era of globalisation, emerging and re-emerging diseases of public health relevance are a concern to developing and developed countries and are a real threat due to the interdependence of the global economy. Communication and analysis systems available should be tailored to meet the global health priorities, and used to develop and constantly improve novel systems for the exploitation of information to generate knowledge.


AUTHOR(S):Antonio Cassone

INSTITUTION(S) :Istituto Superiore di Sanità, Rome, Italy

TITLE OF TALK :Impact of human and animal migrations on infectious diseases


ABSTRACT (max. 300 words, including references) :

As historically documented, exchange of goods, international travel and migration of animals and humans have always been a major determinant of the emergence and spread of infectious diseases. Actually, rapid population mobility and animal migration will reduce, and is already doing so, the differences in infectious disease epidemiology between regions of the world. The movement and repositioning of populations and animals between locations where the prevalence and incidence of infections are markedly different poses current and future challenges to public health. Climate changes particularly concerning insect vectors and poverty/political persecutions are strong factors in geographic repositioning of animals and populations, respectively, Nowadays Europe as a whole, and particularly the countries of the Mediterranean areas are experiencing a rather dramatic increase in South-North and East-West movements of people coming from regions with either much higher prevalence of disease than in Mediterranean countries ( e.g. tuberculosis) or with endemic diseases which were unknown in the Mediterranean area ( e.g. some arthropod-borne viral or protozoal diseases , see the Chagas disease in Spain).Social factors bound to immigration and lack of immigrant integration are also impacting strongly though indirectly on population immunity, thus making people overall more susceptible to infections and non-infectious diseases, as well. Continuous surveillance programs by sentinel networks are critically needed and must be adapted to regional specific situations in order to gain a quasi real-time monitoring of infectious emergence and spreads. In this context, the countries facing on the Mediterranean Area should consider strengthening scientific collaboration that could ultimately also generate a Collaborative, non-burocratic, Surveillance Network aimed to detection and control of old and new microbial threats specially affecting this area of the world. This should not be seen only as a “defensive” action but as a way to build competence, expertise and collaboration which remain the only real weapons to fight infectious threats.


AUTHOR : Gilberto Corbellini

INSTITUTION :Sezione di Storia della Medicina – Sapienza Università di Roma

TITLE OF TALK :Italian contributions to the understanding of malaria ecoepidemiology : a historical account


According to the first Italian health statistics, published in 1887 in that year about 20.000 people died because of malaria infections. Italian health officers estimated that, in the years around 1900 about two millions of clinical cases affected a total population of 30 millions. Malaria disappeared from Italy immediately after the second world war, thanks to a political commitment to fight the causes of the disease, which persisted since 1900, and, finally, because of a systematically planned campaign of DDT spraying launched in 1947. Indigenous malaria mortality stopped in 1948. After a few years, the transmission of both falciparum and vivax was interrupted, and the parasites eradicated.
The eco-epidemiological features of Italian malaria represented a major health, economic and social challenge in the years following the Italian political unification. How and why did Italian governments succeeded in putting malaria under control, in some Italian regions, already at the beginning of the XXth Century, and, finally, in eradicating it from the country ?
Epidemiological, clinical and experimental studies carried on by Celli, Marchiafava, Bignami, Grassi and Missiroli highlighted the entomological and epidemiological factors involved in the variability of the Italian and European malaria ecosystems, and allowed shaping political decisions aimed at implementing effective control measures. The talk will summarize such findings and interventions.
The investigations of the eco-epidemiological features of Italian malaria, especially at the level of mosquitos’ biology, provided new insights to understand sub-Saharan Africa malaria eco-epidemiology. From Italian malariological investigations, carried on mostly under the scientific leadership of Mario Coluzzi during the past five decades, new technical tools and scientific knowledge developed, allowing to place explanations of tropical malaria eco-epidemiology on soundest evolutionary bases.


AUTHOR(S):Amos Etzioni

INSTITUTION(S) :Meyer children hospital, Rambam Campus, Rappaport Scholl of Medicine, Technion, Haifa, Israel

TITLE OF TALK :Primary immunodeficiency in the Middle East : genetic and environmental aspects


ABSTRACT (max. 300 words, including references) :

Primary Immunodeficiency diseases are genetic disorders and thus are much more common in populations where consanguinity is common. Indeed in many of the countries in the middle east this is the case. For example is Israel, which has a small population, several novel primary immunodeficiency syndromes were described including veno-occlusive disease of the liver associated with immunodeficiency (1), leukocyte adhesion deficiency (LAD) type 2 (2) and just recently severe combined immunodeficiency associated with mutation in STIM 1 (important for calcium influx to T cells) (3). Thus the awareness for PID in these countries should be very high in order to diagnose them as early as possible and treat them. It is well known that these case are « medical emergencies » and delay in diagnosis may have fatal consequences.
Due to cultural and religious reasons it is quite difficult to prevent the occurrence of genetic diseases in the middle east region and specific education programs are needed including brochueres in different languages with the famous 10 warning signs for PIDs.
During the talk several examples of these conditions in various ethnical groups in Israel will be discussed to highlights the problems which are quite common in our area for physicians and health care providers dealing with primary immunodeficiency disorders.
References :

  • Etzioni Et al J. Pediatr. 1987
  • Etzioni Et al. NEJM 1992
  • Picard et al. NEJM 2009

AUTHOR(S):Massimo Federico and Monica Pirani

INSTITUTION(S) :Medical Oncology, University of Modena and Reggio Emilia, Italy

TITLE OF TALK :The Olive Tree Project : a cooperation across the Mediterranean Sea for cancer registration


ABSTRACT (max. 300 words, including references) :

According to the World Health Organization (WHO) projections, cancer is a leading cause of death worldwide : it accounted for 7.4 million deaths (around 13% of all deaths) in 2004 and more than 70% of all cancer deaths occurred in low and middle income countries. While the total cancer burden remains highest in resource-rich countries, it is increasing rapidly in resource-poor countries. In Africa, in fact, chronic diseases such as cancers are growing as serious public health challenges. However, in these countries, the cancer control is low on the health agendas, being minimally represented in global health efforts.
In the year 2002 a population-based Benghazi Cancer Registry (BCR) was established under the auspices of the Libyan National Cancer Research Centre. Soon after, a spontaneous collaboration was established between the University of Modena and Reggio Emilia and people involved in the BCR, with the aim of promoting cancer registration in Eastern Libya. So far, this twinning has produced two reports on cancer incidence and mortality in the years 2003 and 2004.
Encouraged by this positive and active partnership, during a meeting in Benghazi (Libya) organized with the participation of International Agency for Research of Cancer (IARC), the Olive Tree Project was launched in October 2008.
The Olive Tree Project represents an attempt for encouraging cooperation among cancer registries lining on both sides of the Mediterranean Sea and improving cancer registration and sharing specific experiences in cancer control, including prevention strategies, diagnostic procedures and treatment opportunities. People attending the Benghazi meeting and approving the project, have focused on the following four objectives :

  • Improving performances of each Cancer Registry ;
  • Expanding scientific and technical cooperation with other Cancer Registries in the Mediterranean Region ;
  • Sharing different experiences ;
  • Promoting cooperative studies.

AUTHOR(S):Abdelali Haoudi, Ph.D.

INSTITUTION(S) :Qatar Foundation, Doha, Qatar

TITLE OF TALK :Research, science and technology at Qatar Foundation : an innovative model for the renaissance of science in the Arab/Islamic world


ABSTRACT (max. 300 words, including references) :

Qatar Foundation is developing a range of science and research capacity building programs to address major needs of the State of Qatar ranging from establishing scientific research programs to creating a critical mass of scientists needed to ensure successful implementation and sustainability of Qatar Foundation’s ambitious research agenda. This also includes the development of a coordinated and integrated research setting to facilitate optimal use of research technology platforms while ensuring the highest standards for the conduct of scientific research through regular monitoring and assessment.
One step towards building a strong foundation for science, research and technology development in Qatar is the development of three research institutes, namely :
Qatar Biomedical Research Institute : The goal of this institute is to deliver personalized medicine that can mitigate or eliminate diseases of high prevalence in Qatar and the region such as birth defects, genetic disorders, cancer and diabetes. The Qatar Biomedical Research Institute focus on programs of bioscience that will lead to new biomarker development, drug discovery and therapeutic vaccines. The implementation of these programs is coordinated with Sidra Medical and Research Center, Weill Cornell Medical College in Qatar and other research partners.
Qatar Environment and Energy Research Institute : The goal of this institute is to ensure the sustainable development of the State of Qatar through providing a diversity of sources in terms of access to energy while protecting the environment of Qatar by supplying cleaner and safer energy consistently. Some promising science and research work will be undertaken in environmental (water resources, built environment, etc) and energy (nanomaterials, fuel cells, reservoir modelling, chemical separation technologies and large storage). The implementation of these programs is coordinated with Texas A&M University at Qatar and other research partners.
Qatar Information & Communication Technology Research Institute : The goal of this institute is to transform the State of Qatar into a modern digital society by enriching the lives of every individual and delivering the promise of a connected knowledge-based environment. The Qatar ICT Research Institute will focus on programs of informatics that are important to transform society in healthcare needs, energy use, environmental protection and self-development technologies. These include computing-intensive applications for modeling and simulating energy and environment, biological and chemical processes as well as visualization modeling for improved human-computer interactions. The implementation of these programs is coordinated with Carnegie Mellon University in Qatar and other research partners.


AUTHOR(S) : Angelos Hatzakis

INSTITUTION(S) : Athens University Medical School

TITLE OF TALK :Pandemic influenza H1N1 in Greece : mitigation strategies


ABSTRACT (max. 300 words, including references) :

The emergence of pandemic influenza A H1N1 prompted the WHO to raise the pandemic alert level. Worldwide surveillance confirms a relatively high transmibility of pandemic influenza A H1N1 but the mortality seems to be very low and limited in ages less than 65 years.
We developed a discrete –time stohastic individual- based simulation model to simulate the spread of pandemic influenza A H1N1 in Greece.
The transmission probabilities were modified to yield age-specific attack rates of the outbreak in the community of La Gloria, Mexico.
The population was assumed to be structured and representing the age distribution, household size and the number and size of schools of the greek population. We assumed standard intervention strategies.
Under no intervention we calculated an illness attack rate of 34,5%. Among all interventions, proactive school closure was found the most effective (reduction of illness attack rate 90%).
Based on this model, we evaluated various pandemic influenza vaccination strategies. Vaccinating high risk groups for complications will have an eligible impact on the overall attack rate. Vaccinating children and young adults (6 months – 24 years) is anticipated to result in overall age specific attack rates within the range of seasonal influenza (5-15%).
Vaccination should proceed early and before initiation of a major wave of epidemic. Vaccination during the wave is predicted to be ineffective.


AUTHOR(S):Hashem Shahin1, Tom Walsh2, Amal Abu Rayyan1, Ming K. Lee2, Jake Higgins2, Karen B. Avraham3, Mary-Claire King2, Moien Kanaan1.

INSTITUTION(S) :1Department of Life Sciences, Bethlehem University, Palestinian Authority ; 2Departments of Medicine and Genome Sciences, University of Washington, Seattle, USA ; 3Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

TITLE OF TALK :Population genomics of hearing loss in the Palestinian population : a model for genetic heterogeneity( oral presentation in Round Table 1 )


ABSTRACT (max. 300 words, including references) :

Recessively inherited phenotypes are frequent in the Palestinian population as the result of a long historical tradition of marriages within extended families. Traditionally, gene localization in these families has been achieved with microsatellite linkage mapping. We demonstrate that genome wide screening with high density SNP arrays is an effective method for pinpointing causative genes and novel loci in consanguineous Palestinian families. In total, we genotyped 84 deaf and 84 hearing sibs or parents, from 21 families, on Affymetrix 250K SNP arrays. We generated deafness-associated homozygosity profiles from the SNP data in each family. We defined a peak of homozygosity as a contiguous region greater than 2MB where SNPs were homozygous for one allele among affected members but discordant (heterozygous or homozygous for the complement allele) from unaffected relatives in the pedigree, either parents or sibs. For 15/21 families the longest homozygous peak mapped to a genomic region that included a known deafness gene. Sequencing the relevant gene from each peak region identified 12 deleterious alleles, 10 of which were novel. They included premature truncations of OTOF, PEJK, TECTA, and TMPRSS3, and a large genomic deletion of OTOA that was mediated by a segmental duplication. The mutational spectrum also included novel missense alleles of LHFPL5, MYO15A, MYO7A and CDH23, which were determined to be pathogenic based on molecular modeling tools. Six of the 21 families harbor mutations in as-yet-unknown genes for inherited hearing loss. SNP-based homozygosity mapping defines the genomic locales of these novel loci with considerable precision.


AUTHOR(S) : Marina Kleanthous

INSTITUTION(S) : The Cyprus Institute of Neurology and Genetics

TITLE OF TALK : Thalassemic Syndroms


ABSTRACT (max. 300 words, including references) :

Thalassemias constitute a major health problem internationally and particularly in the Mediterranean and Euro-Mediterranean countries. Currently, key strategy in the fight against thalassemia is the establishment of national programmes for disease prevention and for the treatment of patients. For the prevention of the disease prenatal diagnosis to couples at risk is provided. Current approaches are mainly based on chorionic villi samples (CVS) analysis while preimplantation genetic diagnosis (PGD) is also provided as an option to couples at risk. A new non invasive prenatal diagnosis (NIPD) based on the analysis of the fetal DNA in maternal plasma is under investigation. The present treatment for β-thalassemia consists of regular, life-long blood transfusions and iron chelation therapy but complications are still prominent, especially among non-compliant patients. At present, allogenic bone marrow (BM) transplantation from a matching donor represents the only cure, but carries many inherent risks and can be taken by only a small fraction of patients. New therapeutic approaches based on pharmacological reactivation of the γ-globin gene for the production of fetal hemoglobin and the gene therapy using autologous bone marrow transplantation (BMT) of genetically corrected haematopoietic stem cells (HSCs) are very promising therapeutic avenues for β-thalassemia. The creation of a scientific network (ITHANET) of experts in this field in Mediterranean and European countries and the development of a corresponding collaborative research infrastructure would greatly accelerate the development of new therapeutic approaches, reduce the cost of treatment and alleviate the suffering of thalassemia patients.


AUTHOR(S):Silvia Naitza, Antonio Cao.

INSTITUTION(S) :Istituto di Neurogenetica e Neurofarmacologia, Consiglio Nazionale delle Ricerche, Cagliari, Italy

TITLE OF TALK :Understanding the genetic determinants of allergic asthma in the Sardinian population.


ABSTRACT (max. 300 words, including references) :

Asthma is a multifactorial disease influenced by genetic and environmental factors. Interest in finding etiologic factors has recently intensified, because of its increasing prevalence and associated mortality. Multiple genetic loci and several gene variants have been recently detected and inferred to contribute to asthma. For most of these genes, their relationship to the pathophysiology of asthma remains conjectural and none appears directly involved in the activation of airway inflammatory processes or allergy. Replication of studies has also been difficult because of the genetic heterogeneity of asthma, the extreme variability in disease expression, the presence of phenocopies, and a marked variety of environmental influences. Analysing a cohort of allergic asthmatics in the Sardinian founder population, where limited genetic and environmental heterogeneity facilitates the study of multifactorial traits, we recently identified IRAK-M (1) as a new asthma susceptibility gene and replicated the association in a genetically distant Italian population. IRAK-M , a negative regulator of the TLR/IL-1R pathways and a master regulator of NF-kB and inflammation, is associated with early-onset persistent asthma and highly expressed in lung epithelia. Thus, our data suggest a link between hyperactivation of the innate immune system and chronic airway inflammation, indicating IRAK-M as a new target for therapeutic intervention against asthma. To better understand the role of IRAK-M in the pathogenesis of asthma, we are analysing IRAK-M variants identified by mutation screening in Sardinians patients affected by allergic asthma to evaluate their functional effect as well as the regulation of IRAK-M expression. To improve our understanding of the genetic basis of this disease we are also conducting a case-control genome-wide association study in an extended sample of allergic asthmatic subjects and healthy controls.
(1) L. Balaci, et al. (2007). IRAK-M is involved in the pathogenesis of early-onset persistent asthma. Am. J. Hum. Genet. , 80:1003-1014.


AUTHOR(S):Charles Pilet

INSTITUTION(S) :Institut de France – Académie des Sciences

TITLE OF TALK :Implications of zoonoses on public health and consequences for the Mediterranean area


ABSTRACT (max. 300 words, including references) :

The risk of infection has become a major concern in public health.
New infectious diseases are appearing. Seventy-five percent of these so-called emerging diseases originate from animals and designated zoonoses. The ones described below have all been transmitted to humans from animals :

  • this was the case for AIDS in the early 80s, the simian origin of the virus was established much later.
  • then came bovine spongiform encephalopathy (BSE), commonly known as mad-cow disease and its impact on the appearance of new forms of the Creutzfeld-Jakob disease.
  • it was followed by SARS (Severe Acute Respiratory Syndrome), which spread from China with a high mortality rate and was a source of great concern in many countries.
  • this was also the case for the H5N1 avian influenza virus which triggered a psychosis as we were told that it would induce a pandemic. The swine influenza outbreak, caused by the influenza A H1N1 virus, took over.

Apart from the significant health crises mentioned above, other pathogens have caused great damage worldwide. We can mention, in Asia, the Nipah virus that first appeared in Malaysian pigs in 1998 and triggered an encephalitis epidemic in farmers. In 1999, the disease had reached Singapore and, in subsequent years, Bangladesh and India with high mortality rates.
The animal reservoir of this paramyxovirus, designated Henipavirus , is the fruit bat . The epidemic appeared after an intense deforestation that brought these animals closer to human settlements, contaminating first pigs then humans.


AUTHOR(S):Rino Rappuoli

INSTITUTION(S) :Novartis Vaccines and Diagnostics, Siena, Italy

TITLE OF TALK :Vaccines : an health insurance of the 21st century


ABSTRACT (max. 300 words, including references) :

Vaccines are moving from being risky, immediate life-savers to a safe, long-term health insurance. A century ago vaccines were introduced to prevent death and disability from diseases that were part of the daily life. Given the high risk of disease, a small threat in vaccine safety was accepted. Devastating diseases such as smallpox, poliomyelitis, tetanus, diphtheria, pertussis, hepatitis B, Haemophilus influenzae , measles, mumps, and rubella, that used to kill or disabilitate millions of people have been eliminated. Meningococcal meningitis, which is perhaps the last disease that in a few hours can attack and kill healthy children and young people, is also on its way to be conquered by vaccination. Vaccines today are usually given to prevent diseases that parents and pediatricians have never seen and in their minds these are no longer immediate life savers but rather tools that improve the quality and duration of life. In agreement with this new vision, thanks to the scientific progress, new vaccines can target infections such as HBV and HPV that increase the risk of cancer a few decades after infection, or pandemic influenza before this happens, and are planning to target chronic, metabolic and neurological diseases. Although some difficult targets such as HIV currently go beyond the reach of vaccination, the new vision of vaccines requires a paradigm shift in mindset of manufacturers, policy makers and vaccine users to develop and deploy vaccines as friendly and safe tools for a global health that covers all ages.


AUTHOR(S):Gideon Rechavi

INSTITUTION(S) :Cancer Research Center, Sheba Medical Center and Sackler School of Medicine, Tel Aviv University, Israel

TITLE OF TALK :Environmental modulation of RNA processing : relevance to cancer and genetic diseases


ABSTRACT (max. 300 words, including references) :

A-to-I RNA editing is a structural change in the RNA sequence catalyzed by the adenosine deaminase acting on RNA (ADAR) group of enzymes that convert adenosine (A) to inosine (I) at specific sites in double strand RNA structures. The ubiquitously expressed ADAR1 is present in two isoforms ; the constitutively expressed p110 and the interferon (IFN) inducible p150. Only a handful of A-to-I editing sites were previously known in the human transcriptome. Using bioinformatic analyses we have recently shown that RNA editing is a widespread phenomenon, affecting some twenty thousand sites and more than 2000 different genes, with the actual number of edited genes being probably much higher. Most of these editing sites reside in Alu elements, the short interspersed elements comprising 10% of the human genome that reside frequently within the non-coding regions of genes, namely 5’ and 3’ untranslated regions (UTRs) and intronic sequences. Recent data show that editing events can be involved in protein recoding, splicing, gene silencing, anti-retroelement defense, augmenting or counteracting the RNAi mechanism, and miRNA biogenesis and expression. RNA editing was also shown to be involved in the regulation of subcellular RNA localization, nuclear anchoring and translation.
We provide evidence that modulation of RNA editing is relevant to a variety of human diseases such as neurodegenerative disorders, cancer, infection and metabolic diseases. RNA editing is emerging as a new global epigenetic modification and may be involved in regulation of gene expression in response to environmental cues.


AUTHOR(S):Giovanni Rezza

INSTITUTION(S) :Department of Infectious Diseases, Istituto Superiore di Sanità

TITLE OF TALK :Human and virus migration in the Mediterranean area : the case of HIV and Chikungunya virus


ABSTRACT (max. 300 words, including references) :

Migration and other forms of human mobility are important determinants of the spread of infectious diseases. Over the last decades, migration among and to Mediterranean has greatly increased. Differences in social and economic factors have played an important role in intra-Mediterranean migration, especially from south to North and from east to west. This may determine a bidirectional flow of viruses. A tyical example is provided by HIV subtype B, which travelled from western to eastern Europe through migrants going back home from migration sites. Transcontinental migration to Mediterranean countries may also be a determinant of the spread of exotic viruses, as recently demonstrated by the outbreak of Chikungunya virus infection occurred in Italy in the summer 2007. For these reasons, studying the flow of human and virus migration through epidemiological and phylogenetic methods is important in order to prevent epidemic events by implementing early intervention.


AUTHOR(S):Giovanni Romeo, Anna Lorusso and Matteo Dutto

INSTITUTION(S) :University of Bologna Medical School and European Genetics Foundation – Bologna (romeo@eurogene.org)

TITLE OF TALK :Training in Genetic Medicine in the Mediterranean area through the web : the role of the European Genetics Foundation for the prevention of emerging genetic diseases


ABSTRACT (max. 300 words, including references) :

Genetic diseases represent a major health problem worldwide. It is nowadays impossible to quantify the whole burden of birth defects and genetic diseases among people of all ages living in the Mediterranean Sea Basin. This will require a detailed collection of genetic epidemiological data and the assessment of needs in the region which in turn will foster the development of Genetic Medicine, one of the condicio sine qua non to ensure enhancement of the quality of life and social progress in the region. To this end the European Genetics Foundation (EGF) is coordinating the MEDITERRANEAN GENETIC MEDICINE (MED-GEN-MED) project whose specific objective is the creation of an interdisciplinary community of young physicians and researchers aimed at improving health care system performance, scientific skills and competences in the Mediterranean Sea Basin. At the same time this specific objective will be achieved by implementing a common information system and a training platform dedicated to the prevention and management of genetic diseases. In this context the courses of the EUROPEAN SCHOOL OF GENETIC MEDICINE (ESGM) organized by EGF during the past 22 years (www.eurogene.org) will contribute to the transfer of knowledge and expertise on these themes across borders in the Mediterranean region. While some ad hoc courses will be addressing specific issues related to major health problems of the Mediterranean area, the traditional ESGM courses will guarantee opportunities for training in the basic topics of Genetic Medicine (Medical Genetics, Molecular Cytogenetics, Cancer Genetics, Statistical Genetics, etc.). All the ESGM courses are usually webcast live via Internet to become Hybrid Courses when one or more University or Hospital groups decide to use the same webcasting to organize local RTC (Remote Training Centers) in their own Institutions. The development of this type of distance learning was stimulated by a grant awarded in 2002 to EGF by the European Commission through the EUMEDIS (EuroMediterranean Information Society) programme. Thus the ESGM courses have been followed by webcasting since 2002 by more than 2000 physicians and researchers interested in Genetic Medicine from all over Europe, the Southern Mediterranean region and the Middle East. The webcasting of the ESGM courses has been made possible so far by grants from the EU and the March of Dimes.


AUTHOR(S):Abdelaziz Sefiani

INSTITUTION(S) :Hassan II Academy of Science and Technology

TITLE OF TALK :Genetic disorders in Morocco


ABSTRACT (max. 300 words, including references) :

Morocco, like other south Mediterranean countries, is facing an accelerating epidemiological transition to non-communicable diseases, resulting in congenital and genetic disorders attaining public health significance with great impact on morbidity and mortality. Genetic conditions in Morocco are heterogeneous and a large number of patients with these conditions are regularly reported by physicians and clinical centers. But the importance of genetic diseases in Morocco is underestimated because the accurate diagnosis of many genetic diseases requires specific clinical expertise and biological testing too expensive for patients or not available in Morocco. The burden of these genetic disorders is increased by the high consanguineous rate, the lack of population awareness on genetic disorders and the absence of a real national health program to prevent disabilities due to genetic disorders.
Molecular data on genetic diseases in Morocco are still limited and concern some relatively common diseases such Beta thalassemia, some neuromuscular diseases, familial hypercholesterolemia and familial Mediterranean fever. For more rare diseases, gene mutations data have been basically identified by foreign teams on Moroccan patients living abroad (more than three millions). Mutations in mendelian diseases reported in patients from Moroccan origin are currently available in the online Moroccan Human Mutation Database (MoHuMuDa).
Meanwhile the decision of health policymakers to incorporate genetic approaches (including DNA diagnosis) into health services as advocated by the WHO, we present a pragmatic approach which allowed us to gradually introduce in Morocco a cost-effective genetic testing into medical practice. At the same time we present some examples of researches we carried out with an international collaboration support. These researches on rare diseases were inspired from our daily medical genetics practice.
Finally and like most genetic centers in low-income countries, we aim that medical application of genomics benefit our patients and their families and contribute to avert that these progress will Widen the gap between north and south Mediterranean countries.


AUTHOR(S):A-J Valleron

INSTITUTION(S) :University Pierre et Marie Curie & Inserm, Paris, France

TITLE OF TALK :Methodological challenges in environmental epidemiology


ABSTRACT (max. 300 words, including references) :

We shall first discuss the definition and limits, if any, of environmental epidemiology. « Environmental factors” are incredibly viewed in a broad sense. They now include not only radiation, infectious agents, and substances in the air, water, and soil, but also lifestyle factors such as diet, tobacco, and alcohol, and even living and working conditions, social, economic, cultural conditions.
We shall then review the methods of measure of the role of environmental factors. In particular multi-level analyses succeed to disentangle the relative parts of individual and collective health factors.
Modern tools of computing science and modeling are more and more widely used in environmental epidemiology. For example, they help to understand the spread of infectious diseases caused by the ever increasing population density and transportation (the two main environmental changes that the man has experienced over the last century).
Finally, we will defend the view that time has come to change the classical paradigm of the epidemiologist who up to now designs and analyses his data within an “hypothesis driven” framework. The increasing availability “on the fly” of environmental databases, the possibility to geocode all subjects of a study population – manually, and soon automatically thanks to the cellular phones- the power of computers and of the geographic information systems, the new data mining statistical techniques open now the way to “ data driven” approaches similar to those used in the whole genome analyses (1).
(1.) Bougneres, P. and A.J. Valleron, Causes of early-onset type 1 diabetes : toward data-driven environmental approaches. J Exp Med, 2008. 205(13) : p. 2953-7.


AUTHOR(S):Suher Zada , Mahmoud ElHefnawy, Eman El Ahwany and Ibrahim Rabie

INSTITUTION(S) :American University in Cairo, National Research Center and Theodor Bilharz Research Institute

TITLE OF TALK :Epidemiology of Schistosomiasis and Fascioliasis in Egypt


ABSTRACT (max. 300 words, including references) :

Schistosomiasis is a disease that ranks with malaria and tuberculosis as a major source of morbidity affecting approximately 210 million people in 76 countries, despite strenuous control efforts .(1) The two species endemic in Egypt are S. haematobium and S. mansoni. Hepatitis C superseded schistosomiasis as a result of latrogenic and biological factors.(2) Praziquatal, is almost exclusively used to treat infection but this does not prevent reinfection.(3,4). Hopefully with the knowledge of the genome of S. mansoni (5) the drug discovery will be accelerated. One of the most economically significant helminth diseases of production animals is fascioliasis(6). Specifically, F. gigantica which infects many breeds of sheep and cattle in tropical regions limits the ability of developing countries to meet the increased global demand for food of animal origin. The latter is expected to increase in such countries by 2020 (7). The ability to develop effective strategies for parasite control requires accurate determination of infection affecting animal productivity. Egypt deserves mentioning because of the emerging situation of human fascioliasis in the Nile Delta area. (8) The magnitude of the problem of fascioliasis, alone or combined with schistosomiasis, and the impact on liver fibrosis in our community needs further attention.
(1) Steinmann, P., et al. (2006) Lancet Infect. Dis. 6, 411–425
(2) Liver Disease in Egypt. (2006) G. T. Strickland, Hepatol , 43, no.5
(3) Doenhoff,M.J.& Pica-Mattoccia (2006) Expert Rev. Anti Infect. Ther. 4, 199–210
(4) Danso-Appiah A, Utzinger J, Liu J, Olliaro P. (2008) Drugs for treating urinary schistosomiasis. Cochrane Database of Systematic Reviews, Issue 3. Art. No. : CD000053. DOI : 10.1002/14651858.CD000053.pub2.
(5) M. Berriman et al. (2009) 460, doi:10.1038/nature08160
(6) Spithill, T.W. et al. (1999) Dalton, J.P. (Ed.), CABI Publishing, Oxon,UK, 465–525.
(7) Delgado,C.,et al. (1999) Inter. Food Policy Research Institute,Washington, D.C.
(8) Periago,M V et al. (2008) Infec Genet Evol, vol 8 pp 51-8

Programme de la 2ème conférence Parmenides