Recommendations of the 2006 Human Variome Project meeting

Abstract

Lists of variations in genomic DNA and their effects have been kept for some time and have been used in diagnostics and research. Although these lists have been carefully gathered and curated, there has been little standardization and coordination, complicating their use. Given the myriad possible variations in the estimated 24,000 genes in the human genome, it would be useful to have standard criteria for databases of variation. Incomplete collection and ascertainment of variants demonstrates a need for a universally accessible system. These and other problems led to the World Heath Organization-cosponsored meeting on June 20-23, 2006 in Melbourne, Australia, which launched the Human Variome Project. This meeting addressed all areas of human genetics relevant to collection of information on variation and its effects. Members of each of eight sessions (the clinic and phenotype, the diagnostic laboratory, the research laboratory, curation and collection, informatics, relevance to the emerging world, integration and federation and funding and sustainability) developed a number of recommendations that were then organized into a total of 96 recommendations to act as a foundation for future work worldwide. Here we summarize the background of the project, the meeting and its recommendations.

Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker

“…In addition, the contribution of sequence variants in particular genes to complex disorders with high population risks is being analyzed in genetic association studies. The use of sequence variation information for these purposes makes it clear that unambiguous and correct descriptions of sequence variants in databases and in the literature are of utmost importance, not in the least since mistakes and uncertainties may lead to undesired errors in clinical diagnosis [den Dunnen and Paalman, 2003;Cotton et al, 2007]. This problem was recognized several years ago, leading to proposals for nomenclature guidelines [Antonarakis et al, 1998], which were extended later [den Dunnen and Antonarakis, 2000].…”

Somatic mutation databases as tools for molecular epidemiology and molecular pathology of cancer: Proposed guidelines for improving data collection, distribution, and integration

“…HVP aims to encourage the use of compatible nomenclature and phenotype reporting systems and to index variant and phenotype data to gene models in the coordinate system generated by HGP. A list of general recommendations has been proposed to promote collection and display of mutations and help the implementation of the HVP [Cotton et al, 2007]. These recommendations cover various areas from data collection, database standards to technical and ethical issues, and are meant to be applicable to all diseases, disorders, and genes.…”

Developing the “next generation” of genetic association databases for complex diseases

“…To this end, the vision of the Human Variome Project (HVP) is "to develop a global collaboration with the aim of building systems and strategies for the collection, storage, interpretation and sharing of human genetic variation and its implications for disease" [Haworth et al, 2011]. Along these lines, the HVP has emphasized the need for disease-specific genetic association databases that would systematically identify and collect the relevant data, quantitatively assess the impact of genetic variants on complex disorders, and make the results available in high-quality, user-friendly databases [Haworth et al, 2011;Cotton et al, 2007]. Independently from the HVP, our group has already developed and continues to maintain a number of such genetic association databases for neuropsychiatric diseases [Allen et al, 2008;Bertram et al, 2007;Lill et al, , 2012 such as AD, PD, ALS, MS, and schizophrenia.…”