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- Craddock, Nick, et al.
(författare)
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Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
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Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
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- Weltzien, Hans Ulrich, et al.
(författare)
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Safe cosmetics without animal testing? Contributions of the EU Project Sens-it-iv
- 2009
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Ingår i: Journal für Verbraucherschütz und Lebensmittelsicherheit. - : Springer Science and Business Media LLC. - 1661-5867 .- 1661-5751. ; 4:suppl. 2, s. 41-48
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Tidskriftsartikel (refereegranskat)abstract
- The 7th Ammendment to the Cosmetics Directive of the European Commission (Directive 76/768/EEC2) bans the marketing of cosmetics containing animal-tested ingredients since March 2009. Excepted are only tests for repeated dose toxicity, for which the animal ban will come into effect by 2013. One major concern for cosmetics, i.e. the risk of containing skin (contact) sensitizers, has in the past been addressed almost exclusively by animal testing. It is this problem attracting the central interest of the integrated research project Sens-it-iv (Novel Testing Strategies for in vitro Assessment of Allergens, http://www.sens-it-iv.eu ), funded by the EC within framework 6 since October 2005. Here, the 28 Sens-it-iv partners from 10 European States present the 5 most promising types of in vitro assays selected for further refinement. These are: (1) a human epidermal equivalent (EE) model to rank contact allergens according to their sensitizing potency, (2) identification of contact sensitizers, including pro-haptens, through intracellular production of IL-18 by the human keratinocyte cell line NCTC 2544, (3) determination of activation markers such as CD86, CD54 and most prominently CXCL8 (IL-8) on/in dendritic cell lines, (4) contact sensitizer-specific migration of MUTZ Langerhans cells towards the chemokine CXCL12, and (5) the allergen-specific activation and proliferation of na < ve human T cells. Ongoing genomic and proteomic experiments are in the process of identifying larger sensitizer-specific biological marker signatures to be integrated into the above assays. We hope to supply the European control agencies with a basis for further validation of in vitro assays by the end of 2010.
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