Anti-DPP10 polyclonal antibody

Background: In the present study we investigated genetic variants associated with bipolar disorder in a homogenous Norwegian sample, and potential genetic overlap with schizophrenia, using the Affymetrix 6.0 array. Methods: We carried out a genome-wide association study (GWAS) by genotyping 620 390 single-nucleotide polymorphisms (SNPs) in a case-control sample of Norwegian origin (the TOP study) including bipolar disorder (n = 194), healthy controls (n = 336) and schizophrenia (n = 230), followed by replication and combined analysis in a genetically concordant Icelandic sample of bipolar disorder (n = 435), and healthy controls (n = 10,258). Results: We selected 1000 markers with the lowest P values in the TOP discovery GWAS and tested these (or their surrogates) for association in the Icelandic replication sample. Polymorphisms on 35 loci were confirmed associated with bipolar disorder (nominal P value<0.05; not corrected for multiple testing) in the replication sample. The most significant markers were located in DLEU2, GUCY1B2, PKIA, CCL2, CNTNAP5, DPP10, and FBN1. The combined group of schizophrenia and bipolar disorder compared to controls did not provide additional significant findings. Limitations: Relatively small number of samples. Conclusions: We detected weak but reproducible association with markers in several genes, in proximity to susceptibility loci found in previous GWAS studies of bipolar disorder. Further work is required to study their localization, expression, and regulation and international meta-analytic efforts will help to further elucidate their role. (C) 2010 Elsevier B.V. All rights reserved.

The use of positional cloning for the identification of complex trait susceptibility genes has gained momentum with the completion of the human genome project. The approach involves the collection of well-phenotyped cohorts (either family-based or case-control designs), the generation of high-density single-nucleotide polymorphism linkage disequilibrium maps, and the application of powerful statistical methods to localize narrow regions of genetic association with disease. In 2003, two novel genes relating to asthma were identified using this approach, PHF11 and DPP10, neither of which had previously been implicated in the pathobiology of either asthma or allergy. In addition, further support for ADAM33 (the first asthma susceptibility gene identified by positional cloning) as an asthma gene was presented, although with mixed results. These discoveries open new avenues for research in asthma and allergy, and highlight the power (and limitations) of positional cloning for the identification of asthma genes, and complex trait genes in general.