Human variome project country nodes: Documenting genetic information within a country

Authors


  • This article is dedicated to the memory of Professor David Rimoin, the first Chair of the Human Variome Project International Scientific Advisory Committee, whose support and overall contribution for the Human Variome Project was tireless and instrumental for its success.

  • Communicated by Mark H. Paalman

Abstract

The Human Variome Project (http://www.humanvariomeproject.org) is an international effort aiming to systematically collect and share information on all human genetic variation. The two main pillars of this effort are gene/disease-specific databases and a network of Human Variome Project Country Nodes. The latter are nationwide efforts to document the genomic variation reported within a specific population. The development and successful operation of the Human Variome Project Country Nodes are of utmost importance to the success of Human Variome Project's aims and goals because they not only allow the genetic burden of disease to be quantified in different countries, but also provide diagnosticians and researchers access to an up-to-date resource that will assist them in their daily clinical practice and biomedical research, respectively. Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council, held on 12th December 2011, during the 2011 Human Variome Project Beijing Meeting. We discuss the steps necessary to maximize the impact of the Country Node effort for developing regional and country-specific clinical genetics resources and summarize a few well-coordinated genetic data collection initiatives that would serve as paradigms for similar projects. Hum Mutat 33:1513–1519, 2012. © 2012 Wiley Periodicals, Inc.

Introduction

The Human Variome Project (HVP; http://www.humanvariomeproject.org) is an international initiative to systematically identify and document pathogenic and benign genomic variations worldwide. The project aims to extract, organize, and curate genome variation data from clinical, medical, and research laboratories. The ultimate goal of this project is to improve translational research strategies and clinical decision-making processes. The HVP is a collaborative consortium of internationally renowned scientists and healthcare professionals working on genomics that are organized into working groups around specific topics to produce standards, specify systems requirements, and address related issues [Cotton et al., 2007; Kaput et al., 2009]. The two main avenues of genome variation data collection are (1) gene/disease-specific collection, and (2) country-specific collection.

The HVP Country Nodes (Table 1) are key to the success of the HVP as they would allow: (1) data sharing among diagnostic laboratories and clinics in each country to support nationwide genetic testing services; (2) data archiving in National/Ethnic mutation databases [NEMDBs; Cotton et al., 2009; Patrinos, 2006] to estimate the genetic burden in each country, hence contributing to better targeting of healthcare planning and policy development; and (3) data sharing between NEMDBs and locus-specific databases (LSDBs) or central data repositories (e.g., NCBI and EBI), in a country-specific ethically compliant manner. Building capacity at the national level also provides a necessary platform for engagement across borders. However, there are many issues involved in establishing and, most importantly, running such a Node.

Table 1. Existing HVP Country Nodes (as of End of December 2011)
 NodeNode representativeURLNEMDBa
  1. aExistence of a centralized HVP Country Node-specific NEMDB.

  2. N/A, not yet available.

1AustralianTimothy Smithhttp://www.hvpaustralia.org.auYes
2AustrianMartina Witsch-Baumgartnerhttp://www.oegh.atN/A
3BelgianThomy de Ravelhttp://www.beshg.beN/A
4ChineseMing Qihttp://www.genomed.org/lovdYes
5CypriotAndreas HadjisavvasN/AN/A
6EgyptianSherifa Ahmed Hamedhttp://www.goldenhelix.orgYes
7HellenicGeorge P. Patrinoshttp://www.goldenhelix.orgYes
8KuwaitiFahd Al Mullahttp://www.al-mulla.orgYes
9MalaysianZilafalil bin Alwihttp://1mhgvc.kk.usm.myN/A
10NepaleseTilak ShreshtaN/AN/A
11SpanishMaría-Jesús SobridoN/AN/A
12VietnameseChí Dũng VũN/AN/A

Here, we report the discussions and recommendations that resulted from the inaugural meeting of the International Confederation of Countries Advisory Council (ICCAC), held on 12th December 2011, during the 2011 HVP Beijing Meeting, in which all existing HVP Country Nodes were represented in addition to several human genetics societies (Box 1) to better pursue the HVP aims and goals through the HVP Country Nodes.

Box 1. The Various National Genetics Societies and Regional Human Genetics Networks That Were Represented in the Inaugural Meeting of the ICCAC in Beijing (in Alphabetical Order)

  • National Genetics Societies

    • American Society of Human Genetics

    • American College of Medical Genetics

    • Austrian Society of Human Genetics

    • Belgian Society of Human Genetics

    • Hellenic Association of Medical Geneticists

    • Spanish Society of Human Genetics

  • Regional Genetics Networks and Societies

    • African Society of Human Genetics

    • Centre for Arab Genomic Studies

    • European Society of Human Genetics

    • Human Genetics Society of Australasia

    • International Federation of Human Genetics Societies

    • Latin American Network of Human Genetics Societies

Human Variome Project Country Nodes in Practice

At present, 12 HVP Country Nodes are represented in the International Confederation of Countries Council of HVP (Table 1), which have been incorporated in HVP from 2010 and are particularly variable in their stage of development. The outline of establishing an HVP Country Node and the recommendations to collect country-specific genetic data are described elsewhere [Al Aama et al., 2011; Patrinos et al., 2011] and as such will not be discussed here.

The Australian HVP Node automatically collects the results of genetic tests performed by Australian Diagnostic laboratories. This genetic data set is stored within a secure repository, which can only be accessed by diagnostics laboratories and medical clinics to assist the diagnosis of patients [Al Aama et al., 2011]. Using this dataset, diagnostics laboratory staff is able to access the cumulative knowledge of every diagnostic laboratory in Australia. The molecular dataset is linked to clinical data housed at hospitals and clinics throughout Australia via the BioGrid service (http://www.biogrid.org.au) and can be accessed by researchers who have obtained approval from a Human Research Ethics Committee.

The Austrian HVP Node is at the moment part of the Austrian Human Genetic Society (Österreichische Gesellschaft für Humangenetik, ÖGH). In Austria, there is neither central registration of patient data nor centralized collection of genetic data. As such, the aim of the Austrian HVP Node will be to create a centralized national platform for sharing genetic knowledge and data and providing an easy way to submit variation data directly to international databases, potentially also of interim storage of such data.

The Belgian HVP Node is represented by the Belgium Society of Human Genetics, which has Board members from all eight centers offering genetic testing services in the country. The Belgian Plan for Rare Diseases was formulated under the chairmanship of emeritus Professor Jean-Jacques Cassiman. This foresees a National registry, which will be coordinated by the Ministry of Social Affairs and public Health. Presently, there are local disease-specific registries, and some laboratories are entering information into LSDBs. Centers of excellence in the field of cystic fibrosis, neuromuscular disorders, and metabolic diseases do exist and more are foreseen.

The Chinese HVP Node has a central role in the entire project. The Node members have already built several databases of genetic diseases, initially focusing on databases of ion-channel cardiac arrhythmias (LQTS1-12, including KCNQ1, KCNH2, SCN5A, KCNE1, KNCE2, KCNJ2, etc.), BRCA1 and BRCA2, mismatch repair genes (MMR), and APC genes for breast cancer, Lynch syndrome, and familial adenomatous polyposis (FAP), respectively, in the Chinese population using the Leiden Open Variation Database (LOVD) format [Pan et al., 2011; Zhang et al., 2010; http://www.genomed.org/LOVD]. Data mining was performed by a group of students formed for this purpose using PubMed and some Chinese search engines to collect all the variants in these genes in the Chinese population.

The Cypriot HVP Node is in its early phase of development and is under the auspices of the Cyprus Society of Human Genetics. At present, only one institution is performing genetic testing at the diagnostic level, whereas many research laboratories are working on the genetics of rare and common diseases. The Cypriot HVP Node is also in the process of establishing a National Genetic database. Presently, the existence of an ETHNOS-based National Genetic database [Kleanthous et al., 2006; http://www.goldenhelix.org/server/cypriot], which is also expanded along the lines of the MED-GENET European Commission project, is expected to facilitate the establishment of the Cypriot HVP Node National Genetic database.

The Egyptian HVP Node is currently run by the Egyptian Neurogenetic Disorders Consortium in Upper Egypt. Egypt has the largest population in the Arab world (about 85 million), with a high percentage (up to 40%) of consanguineous marriages. The Egyptian NEMDB is already available, using the ETHNOS software (http://www.goldenhelix.org/server/egyptian), along the lines of the MED-GENET European Commission project, and can be further expanded to form the basis of the Egyptian HVP Node. Also, the Egyptian National Registry project has been initiated in 2007 for the Genetic Disorders in the National Research Centre, while in the same year the DNA biobank for rare genetic diseases and for subsequent whole genome analysis studies has been established.

The Hellenic HVP Node was formally incorporated in the Human Variome Project in 2010. At present, the Hellenic HVP Node is supervised by a board of 11 geneticists from various Greek academic institutions, most of them sitting at the Board of the Hellenic Society of Human Genetics. The Hellenic HVP Node is endorsed by the Hellenic Bioscientists Association (PEV; http://www.pev.gr; content in Greek) and by the Hellenic Society of Human Genetics (http://www.sige.gr; content in Greek) and has been built around the Hellenic National Mutation frequency database, one of the very first NEMDBs developed in 2005 [Patrinos et al., 2005]. The Hellenic NEMDB and the entire Hellenic HVP Node structure are hosted as a contribution to the HVP within the Golden Helix Server of the Golden Helix Institute of Biomedical Research (http://www.goldenhelix.org). The Hellenic NEMDB, such as the Cypriot and the Egyptian NEMDBs, is based on the ETHNOS software [van Baal et al., 2010]. The existence of the Hellenic NEMDB and the subsequent creation of the Hellenic HVP Node has not only promoted the collection of genomic variation in the Hellenic population but has also encouraged new studies to document the genetic heterogeneity of the most common genetic disorders in various parts of the country [Papachatzopoulou et al., 2010; Samara et al., 2007]. Also, board members of the Hellenic HVP Node participate in a nationwide study that have been recently initiated to critically ascertain the general public's awareness and healthcare professionals' opinion on genetics and genetic testing services in Greece [Mai et al., 2011; Pavlidis et al., 2012; Sagia et al., 2011].

The Kuwaiti HVP Node was incorporated into the Human Variome Project in 2010 in an attempt to propel local scientists and clinicians into the forefront of genetic research [Ozcelik et al., 2010; Tadmouri et al., 2009]. Currently, the Kuwaiti HVP Node is headed by two members from Kuwait University and the Kuwait Medical Genetic Center (KMGC), who aim at three major objectives: (1) Publicize the importance of HVP and the Kuwaiti HVP Node to the health of the Kuwaiti population and its impact on theranostics. To this end, the Kuwait Node members have recruited collaborators from KMGC Clinical geneticists and senior clinical scientists at the KMGC are now involved in the education of physicians, and the public through seminars and lectures directed toward the importance of the HVP effort. (2) Attract private and public funds for research. The Kuwaiti HVP Node members have initiated an important collaboration with Weill-Cornell Qatar to sequence 360 Arabs from all Gulf States and Lebanon using next generation sequencing technology. Also, the Kuwaiti HVP Node has initiated an ambitious collaboration with the Kuwait Medical Students Association entitled “Adopt a gene project” that encourages groups of medical students to attract private funding from local businesses and sequence a single gene per group and submit the data to the appropriate HVP databases. (3) Submit available data to international and already established databases [Tadmouri et al., 2006]. The National registry contains more than 37,000 files for families in Kuwait with diverse and rare genetic disorders. Transferring this information to international databases and the HVP in an ethically appropriate manner has been initiated by depositing the mutations found in gastrointestinal hereditary tumor syndromes to the INSIGHT database (http://www.insight-group.org).

The Malaysian HVP Node is coordinated by the 1Malaysian Human Genome Variation Consortium (1mhgvc), which consists of 60 researchers from 12 Malaysian universities and academic institutions. The research consortium was formed in mid 2010 and received support from the Genetics Society of Malaysia, the Malaysian Society of Human Genetics, the Medical Genetics Society of Malaysia, and the Malaysian Society of Bioinformatics and Computational Biology. Among the objectives of the research consortium is to create the human genome variation map of the major ethnic groups in Malaysia and to study its implications on ethical, legal, and social issues (ELSI); archeogenomics; forensics; and disease genome-wide association studies (GWAS). The Malaysian HVP Node was launched on 9 October, 2010 and during the event, a Malay whole-genome SNP database was launched and has grown in size since then. Currently, a total of 291,718 SNPs from 103 individuals representing the Kelantan, Champa, Banjar, Bugis, Kedah, and Jawa Malay subgroups has been deposited in the database. A mutation database has recently been added to the 1mhgvc databases. Currently, the database contains mutations of the RB1 and the MSX1 genes of the Malay patients and these are regularly updated with new mutations and new genes.

The Spanish HVP Node started in 2010, with the representative office in the Galician Foundation for Genomic Medicine (Santiago de Compostela) and under the auspices of the Board of the Spanish Society of Human Genetics. The first steps undertaken were directed to awareness raising and gathering of support among the genetics community and other relevant biomedical societies in Spain, mostly in meetings of the Spanish Societies of Neurology, Genetics, and Neuroscience, as well as talks to patient support groups. Also, in the fall of 2010 a document on the HVP was produced and presented to several Health and Science administrations, in which benefits, challenges, and solutions regarding collection of genetic variants by the HVP were described. The document contained also a Node development plan with steps and resources needed, as well as considerations on some legal and ethical aspects, with reference to the HVP recommendations [Povey et al., 2010]. The Regional Government of Galicia approved a two-year grant (2009–2010) to support the collection of genetic variation in neurological and psychiatric disorders in Galicia and, specifically, to contribute to the building of LSDBs and to the HVP. Among the next most important aims of the Spanish HVP Node are to join forces with the ongoing effort of the Spanish Registry for Rare Diseases and to contribute to catalyze the Latin American HVP Node.

The Vietnamese HVP Node currently includes only one hospital that has clinical genetics capacity. Also, registries for rare diseases exist in the country that need to be interconnected with the Vietnamese HVP Node. Molecular testing for some monogenic disorders and cancers are available in some centers in the two biggest cities of the country, namely, Hanoi and Ho Chi Minh City.

Finally, the Nepalese HVP Node is represented by an eight-member consortium that includes government representatives. There is active interaction with the Chinese HVP Node. To date, there is no established NEMDB in Nepal, although future plans include the development of such database in collaboration with other HVP Nodes that will also include research partnership, technical, and advanced academic training. To this end, there are some initial discussions with the Hellenic HVP Node to provide expertise to these disciplines, as a result of the Beijing International Confederation of Countries Advisory Council meeting. Also, initial funding from HVP coordinating office and the University Grant Commission in Nepal will greatly facilitate these efforts.

Other countries represented in the meeting were South Africa, the United Arab Emirates, Japan, Philippines, the United Kingdom, the United States, Czech Republic, and Finland, while the Latin America region was also represented. Some of these countries have relevant activities that will form the basis of the HVP Nodes. The above illustrates that although the existing HVP Country Nodes are, at present, at various stage of development, they have the potential to make significant contributions to the benefit of local societies, for example, by stratifying molecular diagnostics services, particularly in large heterogeneous populations or by increasing genetics awareness of various stakeholders. Also, the existence of these HVP Country Nodes can motivate the development of other HVP Country Nodes for countries interested to join this international initiative.

Discussion

Over the last decade, various initiatives have been established to capture and archive the genetic heterogeneity in various populations and ethnic groups worldwide (e.g., International HapMap project, 1000 Genomes Project, and Pan-Asian personal genomics initiative). NEMDBs, a large number of which reside in developing countries, aim to extend the effort and fulfil the need to create more comprehensive databases of genetic variants [Patrinos, 2006] by ensuring a thorough documentation of common and rare genetic diseases in each population. For developing countries, a set of recommendations have been recently proposed [Patrinos et al., 2011], that would enable developing countries to better orchestrate the process of capturing genetic variation data linked to pathologies.

One of the stated goals of HVP, as outlined during the inaugural [Melbourne, Australia; Cotton et al., 2007], planning [Costa-Brava, Spain; Kaput et al., 2009], and implementation meetings [Paris, France; Kohonen-Corish et al., 2010] is the realization of the HVP Country Nodes, possibly acting as the locomotive of the entire initiative. However, there are several issues that should be taken into consideration not only while establishing and managing an HVP Country Node but also while coordinating the entire effort. These issues, which have been discussed during the inaugural meeting of the International Confederation of Countries Advisory Council, are outlined below.

Model HVP Country Nodes

There are substantial variations regarding the degree that existing HVP Country Nodes are developed and their activities deployed in the corresponding countries. Despite the fact that most of the HVP Country Nodes have only recently been officially admitted to HVP, some of them, such as the Australian, Chinese, Hellenic, and others have been built around existing structures, such as a NEMDB. However, it has been agreed that at the moment there is no model HVP Country Node because level of development of the Node, genetic, and cultural composition of each country is unique. Also, the International Confederation of Countries Advisory Council noted that the level of development of an HVP Country Node should not be the sole criterion to consider a Country Node as a model because the genetic and cultural composition of each country is unique. An important parameter for assessment of country efforts is whether the HVP Country Node has deployed its activities in concordance with the HVP guidelines and recommendations, as previously described [Al Aama et al., 2011; Patrinos et al., 2011]. Considering the situation in developed countries, such as the United Kingdom, where the genetic services operate in a very organized manner, each HVP Country Node could operate by establishing HVP country-specific councils in various places/cities rather than a Country Node as a whole. This model is consistent with the model adopted by the European Pharmacogenomics for Every Nation Initiative (PGENI; http://www.pgeni.org) Regional Center with the adoption of PGENI Country Councils, consisting of scientists from the entire country and the number of Council members is largely dependent upon the population size [Mitropoulos et al., 2011]. In any case, defining the “model HVP Country Node” is a challenging goal and this issue can be, at least initially, resolved by establishing a consensus on minimum data content and system requirements, data sharing, and database model standards.

Areas Requiring Standards and Guidelines for Countries

The different areas requiring standards and guidelines for countries were also among the issues discussed during the meeting. The development and management of an HVP Country Node requires the adoption of certain standards, guidelines, and recommendations to assure reliability and validity of the data. An initial set of recommendations have been previously issued, particularly for developing countries [Patrinos et al., 2011], whereas some standards and recommendations already exist for other types of databases (http://www.gen2phen.org), relating to genotype and phenotype object models, mutation database models, LSDB-in-a-box platforms, a minimal content list, a data exchange format, a variation ontology, stable reference sequences for genome regions, and digital identifiers for databases, bioresources, and researchers [Celli et al., 2012; Vihinen et al., 2012; Webb et al., 2011]. There is a need to agree on standards, contents and data models for NEMDBs. This will allow data exchange and integration with other NEMDBs and databases, such as LSDBs, as well as development of software tools. An initial set of recommendations for the ideal content of an NEMDB has been previously suggested [Patrinos, 2006], based on which the ETHNOS NEMDB software was developed [van Baal et al., 2010], which is currently being upgraded [Tzimas et al., 2012]. Development of new software in every country would be unnecessary waste of resources and easily lead to large number of isolated databases, which cannot be connected to other resources. ETHNOS could be developed to become such software for NEMDBs. Selecting the latter option is preferred by the attendees of the HVP Council and by some HVP Country Nodes that already use the ETHNOS software for their NEMDBs. The meeting attendees also expressed preference to employ this software for the establishment of NEMDBs in other HVP Country Nodes. The adoption and upgrade of existing software will not only expedite the establishment of new HVP Country Nodes, but will also facilitate the development of existing NEMDBs, by their faster migration to the upgraded software version. We hope a standard will be agreed upon in the near future. Equally important is the assembly and curation of population-specific data collection to ensure that absolute frequencies of disease causing and clinically relevant genome variation are obtained for these populations, particularly those with a high consanguinity rate [Gialluisi et al., 2012].

Software and Systems Between NEMDBs and LSDBs and Strategies for Data Sharing

One of the most critical parameters for the operation of the HVP Country Nodes is the software and systems requirements to accommodate data deposition in each Node and, most importantly, the ability to share and exchange data among different HVP Country Nodes, LSDBs and central repositories. To this end, two main options exist: (1) A gigantic central NEMDB that will be developed for the needs of the HVP that would accommodate all population/ethnic specific datasets, and (2) individual NEMDBs in each HVP Country Node that would be preferably based on the same interoperable Web-enabled platform. The FINDbase database, which was developed for clinically relevant genome variation allele frequencies [http://www.findbase.org; van Baal et al., 2007] may be used as a central unified system [Georgitsi et al., 2011a,b], since the software documents causative mutation and pharmacogenomic marker allele frequencies at a summary level. The interoperable NEMDB approach for data gathering and sharing, which is based on data warehousing principles, has several advantages: (1) databases can be managed and curated from each HVP Country Node representatives, (2) data homogeneity can be ensured since individual NEMDBs will function under the same software, (3) individual population differences, such as social, religious, ethnic differences, can be addressed by minimal software customization without affecting the key functionalities of the main system. Such an approach has already been successfully implemented in the Israeli NEMDB [Zlotogora et al., 2007, 2009], and (4) data gathering can be expedited by assuming a local rather than a central coordinating role. The latter approach has been previously suggested [Patrinos, 2006] and implemented in existing NEMDBs [Georgitsi et al., 2011b; van Baal et al., 2007]. NEMDB database interoperability is also possible not only among NEMDBs that are based on different platforms but also among NEMDBs and other types of databases, for example, LSDBs or central databases. To this end, Café Variome (http://www.cafevariome.org) has been designed to serve as an exchange portal for gene variant (mutation) data. This portal offers users a forum to announce, discover and acquire a comprehensive listing of observed neutral and disease-causing gene variants in patients, unaffected individuals and even populations and, as such, it enables holistic searching across various databases.

In addition to these suggestions and advances, the success of data gathering can be boosted with incentives for data submitters such as microattribution [Giardine et al., 2011] or by encouraging submission of population specific datasets to specialized database journals [Patrinos and Petricoin, 2009] or regulatory incentives [Cotton et al., 2009].

Patient Registries and Other Possible Synergies

Patient registries or clinical genetic databases are equally important aspects of the HVP Country Nodes as summary-level NEMDBs. Patient registries usually contain individual-level data including important genotype–phenotype information that are either maintained locally in hospitals and clinical centers or are big national and some time multicenter supranational initiatives, such as the CFTR2 project (http://www.cftr2.org). However, the establishment and maintenance of patient registries as individual-level clinical genetic databases is a far more demanding task than the development of summary-level NEMDBs. One of the most important challenges is the vital need to ensure patients' anonymity, which dictates removing or safeguarding (e.g., behind firewalls or by encoding) patients' personal information so that they cannot be linked back to their own detailed genotype and phenotype/clinical information. This is particularly important for rare disorders, where one's phenotypic information can reveal his/her identity. This parameter also touches upon the development of databases for clinical trials, which derives from the explosion of individualizing therapeutic interventions. Interconnecting patient registries with mutation databases has been recently discussed [Auerbach et al 2011; Ayme et al 2011], and this combination would be of utmost importance not only for common but also for rare diseases. In actual fact, few HVP Country Nodes, such as the Spanish, the Hellenic, and the Vietnamese HVP Nodes plan or have already joined forces with the corresponding rare disorders registries.

Listing of Needs

To successfully maintain the existing HVP Country Nodes, to encourage the establishment of new Nodes, and to expand HVP and thereby deliver improved healthcare, additional steps need to be undertaken (summarized in Box 2)

First, a need exists to strengthen the role of the International Confederation of Countries Advisory Council since the Country Nodes will play a vital role in the efforts of the HVP. At the same time, each HVP Country Node and accompanying NEMDB, should bear an electronic seal of HVP as a quality feature, indicating that all necessary recommendations, standards, and guidelines are followed. A dedicated Committee or Working group from the International Confederation of Countries Advisory Council will be responsible to assign this quality feature and monitor the Country Node to ensure it continues to conform to the standards agreed. Reciprocally, the corresponding Human Genetics Societies should formally endorse their Country Node to be admitted to the International Confederation of Countries.

Also, careful consideration and planning of the long-term financial stability and sustainability of each HVP Country Node is an absolute requirement. Viable financial planning by the local HVP Country Node must accompany the country's application and possibly a detailed Strength/Weakness/Opportunities/Threat (SWOT) analysis to allow the HVP Country Node Council to evaluate the feasibility of the proposed approach and the ability of the applicants to successfully establish and manage the Node. Fund raising should be sought locally, such as from governments, national grants, charities, patients' organizations, or others. Similarly, the HVP could also facilitate fund raising efforts by providing grants for the start-up and the initial operation of the Node. Besides grants for start-up of Nodes, funding could also be provided centrally by HVP, for example, to upgrade the NEMDB software, to organize educational and/or outreaching activities, and so on. Funding assistance is particularly important for developing countries.

Consortium members, particularly those from countries having close ties with international organizations like UNESCO and WHO, indicated the importance of these organizations, particularly when speaking to their own governments through Ministries of Health, and Ministries with mandates for science, research, and education. HVP has the status of an international nongovernmental organization in operational relations with UNESCO, which facilitates cooperation with the United Nations. UNESCO has some 56 field offices throughout the world with headquarters in Paris. In addition, UNESCO has a global network of national cooperating bodies known as National Commissions for UNESCO, set up by their respective governments. Presently, there are 197 National Commissions for UNESCO across the world, which operate for the purpose of associating their governmental and nongovernmental bodies in education, sciences, culture, and communication with the work of the Organization. HVP Country Nodes are encouraged to build relationships with their respective UNESCO National Commissions and field offices in areas of UNESCO's mandate. With regard to WHO, as it has a complex structure of approximately 150 country offices, 6 regional offices, and a headquarter in Geneva, building relationships with it are complex. With WHO having a core mandate focusing on public health and its governance being largely in the hands of Ministers

Box 2. Recommendations for Development of HVP Country Nodes

  • Political measures

    • Empowerment of the HVP International Confederation of Countries Advisory Council.

    • Develop quality standards and follow their implementation. HVP Country Nodes would have a permission to show HVP seal as a quality feature, to indicate that all necessary recommendations, standards, and guidelines are followed.

    • Formal endorsement of each country's application to become an HVP Country Node by the respective national Human Genetics and Genomics Society.

    • Agreement on distribution of anonymized information.

    • Advocacy with governments: (1) in particular Ministries of Health for awareness of and support for genetic- and genomic-related health in their national health plans; and (2) through Ministries responsible for education, science, and research and through the National Commissions for UNESCO in each country for awareness and support for capacity building in genomics and bioinformatics research and education.

  • Financial measures

    • Careful consideration and planning of a long-term sustainability upon application to become an HVP Country Node.

    • Fund raising from local sources, such as national grants, philanthropic organizations, and patients' organizations.

    • Financial support by the HVP International Coordinating Office for the start-up and the initial operation of the Country Node, particularly for developing countries.

    • Financial support by the HVP Central office for software upgrade and maintenance, for organizing educational and outreaching activities.

  • Other measures

    • Tackling ethical, legal, and societal issues, particularly where patient registries are involved.

    • Adopt a country-specific data gathering and sharing approach.

    • Provision of education for the general public and healthcare professionals on issues relating to genetics and genomics.

    • Development of standards, recommendations, and data models for NEMDBs and encouragement of their implementation to software products.

of Health, it is important for HVP Country Nodes to develop good relationships with their national Ministries of Health based on how Country Nodes can contribute to the health and well being of the populations they serve.

Media coverage in the national and international arena can add to highlighting the importance of the local HVP effort and improving public knowledge of genetics, genomics, and health. Careful consideration needs to be given to how Country Nodes can best be supported in managing positive relationships with various types of local media. A major aim for the next 12 months is to begin work toward globally agreed standards for databases as well as invite more countries to establish Nodes.

Conclusions

The success of existing HVP Country Nodes and progress on multiple other planned national platforms underscores the potential value of the HVP Country Node concept. HVP Country Nodes would best be served by coordinating their efforts promoted by the International Confederation of Countries Advisory Council meeting, as described above. A crucial parameter that would guarantee the successful outcome of these efforts is collaborative work of partners from all over the world, which will save time and effort, improve knowledge generation for all, and will result in better local and global solutions for genomic medicine.

Overall, HVP Country Node operational guidelines will help expand the establishment of centers focusing on genome medicine, which will in turn facilitate the fulfillment of the HVP goals toward a comprehensive worldwide genome variation data collection.

Acknowledgements

We are indebted to Professor Anthony J. Brookes for critically reading of this manuscript and for his valuable comments.

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