André G. Uitterlinden*#^, Pascal P. Arp*, Yue Fang*, Fernando Rivadeneira*#, Joyce B.J. van Meurs*, Huib A.P. Pols*#
Departments of *Internal Medicine, #Epidemiology&Biostatistics,
^Clinical Chemistry, ErasmusMC, Rotterdam, The Netherlands.
Our main research line is to identify and analyse the role of genetic risk factors in common age-related complex diseases. We focus on locomoter diseases (osteoporosis and osteoarthritis) and other endocrine diseases and traits (diabetes, menopause, CVD). We do this by candidate gene studies, analysing “DNA polymorphisms” (among which SNPs) in epidemiological population studies and in patient case-control series for association with disease, and by investigating the underlying molecular mechanisms. We study candidate genes of particular pathways, to find polymorphisms (by bio-informatics and lab research) and subsequently developing robust assays to perform high throughput genotyping in large DNA collections from well-characterized epidemiological study populations. The research provides insight in which and how genetic factors are explaining inter-individual differences for risk-of-disease and response-to-treatment in clinically important common age related diseases. The results are expected to have impact on diagnostics and treatment modalities for these diseases.
We are mostly studying subjects from the The Rotterdam Study, a collection of >10.000 elderly men and women who are being followed for several age-related chronic diseases. In addition, we are coordinating a large multicentre EU-sponsored collaboration (GENOMOS; QLK6-CT-2002-02629) involving >25.000 subjects to identify genetic risk factors for osteoporosis by prospective meta-analyses.
Our current approach is to analyse -per experiment- a few SNPs but in many gDNA samples. The laboratory has a medium-throughput genotyping facility including a Zymark ALH 3000 pipetting robot (including a TwisterII, and integrated plate sealer, plate reader (OD260/280), and PCR machine (ABI 9700, 2x384)), an ABI7900HT Taqman, a WAVE 3500HT dHPLC, and an ABI3100 sequencing machine. The Zymark liquid handling system allows normalization of gDNA samples, plating (to 96 and 384 wells) and automated PCR reactions. The genotying facility has been partly sponsored by NWO (911-03-012) and is part of the ErasmusMC Biomics core facility. The most frequently applied genotyping method in our lab is currently the Taqman method using the ABI assay by design and by demand service. We will report on our lab set-up and experience with Taqman.
Contact: Genetic Lab, Ee575, a.g.uitterlinden @ erasmusmc.nl; Tel: 010-4087573