Analysis of Genetic Variation in the GenomEUtwin Project

Abstract

Multiallelic short tandem repeat polymorphisms, or microsatellites, are useful markers in genome wide scans to identify chromosomal regions containing genes underlying disease loci. The biallelic single nucleotide polymorphism (SNP) can be used to fine map previously identified large candidate regions or to test functional candidate genes by association analysis. In the GenomEUtwin project the population based impact of susceptibility genes for six multifactorial traits will be studied. A genome wide panel of informative human microsatellite markers will be analyzed by fluorescent capillary electrophoresis in well characterized twin and population samples. Contrary to microsatellites, selection of the most informative panels of SNPs is hampered by imperfect data on the allele frequencies and population distribution of SNPs markers in the databases. Therefore, selection of SNPs requires a substantial amount of bioinformatics, and, the SNPs need to be validated experimentally in the relevant populations prior to genotyping large sample sets. In the GenomEUtwin project, large scale genotyping of SNPs will be performed using the SNPstreamUHT and MassARRAY genotyping systems that are based on the primer extension reaction principle combined with fluorescent and mass spectrometric detection, respectively. Production of the genotyping data will be a joint effort by GenomEUtwin partners at the University of Helsinki, the National Public Health Institute in Helsinki, Finland and Uppsala University, Sweden. All genotyping data will be stored in a common database established specifically for the GenomEUtwin project, from where it can be accessed by the twin research centres that provided the samples for genotyping.