The SQL source code, sources and binaries of the client applications (NT and Windows95/98 platforms) and additional documentation are available at http://www.mucosa.de/.

Microsatellite allele data have long been plagued by size shifts that can at best make it difficult to accurately assign genotypes to allele products, and at worse can cause whole batches of data from different instruments, dates or laboratories to be incorrectly assigned. Although modern genotyping technology (capillary electrophoresis) has overcome many of these problems, concern remains regarding the consistency of scores within a laboratory over time and between laboratories when combining data from multiple sources into a single analysis. There remain a large number of laboratories using older technologies or combining data from multiple sources. In addition, thousands of data sets that could potentially be expanded as samples become available are generally regarded as unusable because of the effort that would be required to validate congruence of genotypes from old and new data sets. We present methods to normalize and bin alleles from multiple data sources using a relatively small set of controls and the freely available program allelogram.

Availability of high quality SNP data is a rate-limiting factor in understanding the impact of genetic variability on gene function and phenotype. Although global projects like HAPMAP generate large numbers of SNPs in an even spacing throughout the human genome, many variation studies have a more focused approach: in the follow-up of positional association findings, candidate gene studies, and functional genomics experiments, knowledge of all variations in a limited amount of sequence (e.g., a gene) is needed. This leads to a large number of resequencing experiments, for which there is a surprising lack of analysis software. We have thus developed specialized software (InSNP) for targeted mutation detection and compared its performance to Polyphred and Mutation Surveyor using 28 amplicons. Out of a total of 579 (InSNP), 644 (Polyphred), and 526 (Mutation Surveyor) SNP predictions, 39 SNPs were confirmed by human expert inspection, with five SNPs missed by Polyphred and one missed by InSNP using the default settings. For InDel detection, out of 70 (InSNP), 28 (Polyphred), and 693 (Mutation Surveyor) InDel predictions, two InDels were confirmed by human expert inspection, with one InDel missed by Polyphred. InSNP provides a user-friendly interface with better functionality for mutation detection than general-purpose sequence handling software. It provides similar SNP detection sensitivity and specificity as the public domain and commercial alternatives in the investigated dataset. We hope that InSNP lowers the barriers to the use of automated mutation detection software and aids in the improvement of the efficiency of such experiments. The Windows installer (setup) program and sample datasets are available at www.mucosa.de/insnp/.

Functional annotation of SNPs (as generated by HapMap (http://www.hapmap.org) for instance) is a major challenge. SNPs that lead to single amino acid substitutions, stop codons, or frameshift mutations can be readily interpreted, but these represent only a fraction of known SNPs. Many SNPs are located in sequences of splicing relevance-the canonical splice site consensus sequences, exonic and intronic splice enhancers or silencers (exonic splice enhancer [ESE], intronic splice enhancer [ISE], exonic splicing silencer [ESS], and intronic splicing silencer [ISS]), and others. We propose using sets of matching DNA and complementary DNA (cDNA) as a screening method to investigate the potential splice effects of SNPs in RT-PCR experiments with tissue material from genotyped sources. We have developed a software solution (SNPSplicer; http://www.ikmb.uni-kiel.de/snpsplicer) that aids in the rapid interpretation of such screening experiments. The utility of the approach is illustrated for SNPs affecting the donor splice sites (rs2076530:A>G, rs3816989:G>A) leading to the use of a cryptic splice site and exon skipping, respectively, and an exonic splice enhancer SNP (rs2274987:C/T), leading to inclusion of a new exon. We anticipate that this methodology may help in the functional annotation of SNPs in a more high-throughput fashion.

Single-nucleotide polymorphism (SNP) genotyping is a fundamental tool in the rapidly growing area of complex diseases and pharmacogenomics. SNP patterns that correlate with disease or response to treatment, respectively, are identified using bioinformatic techniques. We present an integrated laboratory information and management system (LIMS) for our high-throughput TaqMan™-based SNP genotyping platform. Three new client tools (ProjectManager, AssayManager, OrderTool) for our LIMS improve quality control and workflow management. The programs support organizing multiple genotyping experiments as projects, managing reagents with barcodes, and automation of assay ordering. The tools are freely available at our homepage.