The remarkable progress in characterizing the human genome sequence, exemplified by the Human Genome Project and the HapMap Consortium, has led to the perception that knowledge and the tools (e.g., microarrays) are sufficient for many if not most biomedical research efforts. A large amount of data from diverse studies proves this perception inaccurate at best, and at worst, an impediment for further efforts to characterize the variation in the human genome. Since variation in genotype and environment are the fundamental basis to understand phenotypic variability and heritability at the population level, identifying the range of human genetic variation is crucial to the development of personalized nutrition and medicine. The Human Variome Project (HVP; http://www.humanvariomeproject.org/) was proposed initially to systematically collect mutations that cause human disease and create a cyber infrastructure to link locus specific databases (LSDB). We report here the discussions and recommendations from the 2008 HVP planning meeting held in San Feliu de Guixols, Spain, in May 2008.

An ambitious plan to collect, curate, and make accessible information on genetic variations affecting human health is beginning to be realized.It has been 60 years since the first variation causing inherited disease was defined at the protein level. Currently, at least one such mutation is known to have occurred in 3000 of the 20,000 recognized human genes. In the next few years, the number of genes in which disease-causing mutations are recognized will increase dramatically. Despite good intentions, efforts to develop and build databases have failed to keep up with this pace.Thus, clinicians and diagnostic laboratories must waste their time trawling through many publications and databases to determine whether a mutation found in a patient has been previously characterized. Availability of previous characterizations of all mutations and their effects would allow them to base their diagnoses and prognoses on evidence rather than guesswork and conjecture. For inherited diseases, rapid access to curated information on all mutations in all genes from all populations is needed. Note that those who gain most by the availability of up-to-date gene variant data are usually downloading information only and are failing to add their findings to further improve the quality of the data collected. Changing this attitude and collecting all data seem to be mammoth tasks, but they are essential.

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ABSTRACT:The May 2009 Human Variome Project (HVP) Forum ''Towards Establishing Standards'' was a round table discussion attended by delegates from groups representing international efforts aimed at standardizing several aspects of the HVP: mutation nomenclature, description and annotation, clinical ontology, means to better characterize unclassified variants (UVs), and methods to capture mutations from diagnostic laboratories for broader distribution to the medical genetics research community. Methods for researchers to receive credit for their effort at mutation detection were also discussed.

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.

The need for Locus-Specific Databases, with disease-specific experts and curators, is an essential ingredient in a process to enable the benefits of the advances in sequencing and mutational analysis to be realized across the genome. Next generation sequencing provides both astounding opportunities and challenges, especially for genetic counsellors. An approach coordinated at a genome wide, international level, supported by well-organized disease-specific respected organizations is a model most likely to be successful, but committed resourceful professionals working in local poorly resourced environments can make valuable contributions that can grow. Bioinformatic tools to sift and integrate multiple domains of information are being developed, and play a major part in meeting the challenges. Regulation of providers, including a requirement for them to submit mutational information to central databases, also should assist to reach the goals needed to realize the opportunities. There is also a need to agree on governance of Locus-Specific Databases (LSDBs) at an international level, and for adequate international funding to support this need, to ensure humanity reaps the benefits of the current molecular genetic revolution. The Human Variome Project offers this, working also with the other major initiatives with similar objectives. This report concludes with Recommendations for the Human Variome Project stemming from the presentations and discussions at the meeting.