Search

High-throughput experimental methods such as medical sequencing and genome-wide association studies (GWAS) identify increasingly large numbers of potential relations between genetic variants and diseases. Both biological complexity (millions of potential gene-disease associations) and the accelerating rate of data production necessitate computational approaches to prioritize and rationalize potential gene-disease relations. Here, we use concept profile technology to expose from the biomedical literature both explicitly stated gene-disease relations (the explicitome) and a much larger set of implied gene-disease associations (the implicitome). Implicit relations are largely unknown to, or are even unintended by the original authors, but they vastly extend the reach of existing biomedical knowledge for identification and interpretation of gene-disease associations. The implicitome can be used in conjunction with experimental data resources to rationalize both known and novel associations. We demonstrate the usefulness of the implicitome by rationalizing known and novel gene-disease associations, including those from GWAS. To facilitate the re-use of implicit gene-disease associations, we publish our data in compliance with FAIR Data Publishing recommendations [] using nanopublications. An online tool () is available to explore established and potential gene-disease associations in the context of other biomedical relations. [ABSTRACT FROM AUTHOR]

Duplicons, that is, DNA sequences with minimum length 10 kb and a high sequence similarity, are known to cause unequal homologous recombination, leading to deletions and the reciprocal duplications. In this study, we designed a Multiplex Amplifiable Probe Hybridisation (MAPH) assay containing 63 exon-specific single-copy sequences from within a selection of the 169 regions flanked by duplicons that were identified, at a first pass, in 2001. Subsequently, we determined the frequency of chromosomal rearrangements among patients with developmental delay (DD) and/or congenital malformations (CM). In addition, we tried to identify new regions involved in DD/CM using the same assay. In 105 patients, six imbalances (5.8%) were detected and verified. Three of these were located in microdeletion-related regions, two alterations were polymorphic duplications and the effect of the last alteration is currently unknown. The same study population was tested for rearrangements in regions with no known duplicons nearby, using a set of probes derived from 58 function-selected genes. The latter screening revealed two alterations. As expected, the alteration frequency per unit of DNA is much higher in regions flanked by duplicons (fraction of the genome tested: 5.2%) compared to regions without known duplicons nearby (fraction of the genome tested: 24.5–90.2%). We were able to detect three novel rearrangements, including the previously undescribed reciprocal duplication of the Williams Beuren critical region, a subduplicon alteration within this region and a duplication on chromosome band 16p13.11. Our results support the hypothesis that regions flanked by duplicons are enriched for copy number variations.European Journal of Human Genetics (2006) 14, 180–189. doi:10.1038/sj.ejhg.5201540; published online 14 December 2005 [ABSTRACT FROM AUTHOR]

Highlights a landmark paper that describes and discusses the finished version of the human genome. Confirmation of the finished human genome sequence as a robust resource for large-scale evolutionary, functional and comparative analyses; Analysis of the gene birth and gene death in humans; Importance of sequencing multiple genomes.

The author reflects on the development of Genome-Wide Association Studies (GWAS). He emphasized that it can be use as an accurate tool to deal with the complete genome for disease gene search without segregation information. He stressed that it include the evolution of giga-sequencing machines such as the Roche/454, Solexa-Illumina and ABI which enabled its users to tackle molecular questions.

Editorial. Cites the insights of the articles published in volume 10 of the journal 'European Journal of Human Genetics.' Emphasis on the molecular and clinical aspects of human gentics; Status of a specific genetic disorders.

Editorial. Discusses the changes that happened in the periodical 'European Journal of Human Genetics' (EJHG). Aim of EJHG publishers for monthly publication; Impact of the increase in interest in publishing in the EJHG; Implementation of a thriftier page layout.