Capturing all disease-causing mutations for clinical and research use: Toward an effortless system for the Human Variome Project

Abstract: The collection of genetic variants that cause inherited disease (causative mutation) has occurred for decades albeit in an ad hoc way, for research and clinical purposes. More recently, the access to collections of mutations causing specific diseases has become essential for appropriate genetic health care. Because information has accumulated, it has become apparent that there are many gaps in our ability to correctly annotate all the changes that are being identified at ever increasing rates. The Human Variome Project (www.humanvariomeproject.org) was initiated to facilitate integrated and systematic collection and access to this data. This manuscript discusses how collection of such data may be facilitated through new software and strategies in the clinical genetics and diagnostic laboratory communities.

[1]  R. Cotton.  Recommendations of the 2006 Human Variome Project meeting , 2007, Nature Genetics.

[2]  C. Sallée,et al.  Locus‐specific databases: from ethical principles to practice , 2005, Human mutation.

[3]  P. Kwok,et al.  Human Variome Project: an international collaboration to catalogue human genetic variation. , 2006, Pharmacogenomics.

[4]  Johan T den Dunnen,et al.  Improving sequence variant descriptions in mutation databases and literature using the Mutalyzer sequence variation nomenclature checker , 2008, Human mutation.

[5]  George P Patrinos,et al.  Hellenic National Mutation Database: a prototype database for mutations leading to inherited disorders in the Hellenic population , 2005, Human mutation.

[6]  George P Patrinos,et al.  National and ethnic mutation databases: recording populations' genography , 2006, Human mutation.

[7]  J. Bond,et al.  The CDKN2A database: Integrating allelic variants with evolution, structure, function, and disease association , 2004, Human mutation.

[8]  R. Cotton,et al.  Quality control in the discovery, reporting, and recording of genomic variation , 2000, Human mutation.

[9]  Meenal Patel,et al.  PTC124 targets genetic disorders caused by nonsense mutations , 2007, Nature.

[10]  R. Cotton,et al.  A survey of locus-specific database curation , 2007, Journal of Medical Genetics.

[11]  Toshio Kojima,et al.  Planning the Human Variome Project: The Spain report , 2009, Human mutation.

[12]  D. Ravine,et al.  Analysis of published PKD1 gene sequence variants , 2007, Nature Genetics.

[13]  Sue Povey,et al.  Sharing data between LSDBs and central repositories , 2009, Human mutation.

[14]  Christophe Béroud,et al.  Genotype–phenotype analysis in 2,405 patients with a dystrophinopathy using the UMD–DMD database: a model of nationwide knowledgebase , 2009, Human mutation.