Biomedical subjects

Peter De Rijk

Publications and source records attributed to Peter De Rijk.

7 recordsLinked to original sources

PubMed2005

High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy.

Two extended haplotypes exist across the tau gene-H1 and H2-with H1 consistently associated with increased risk of progressive supranuclear palsy (PSP). Using 15 haplotype tagging SNPs (htSNPs), capturing >95% of MAPT haplotype diversity, we performed association analysis in a US sample of 274 predominantly pathologically confirmed PSP patients and 424 matched control individuals. We found that PSP risk is associated with one of two major ancestral H1 haplotypes, H1B, increasing from 14% in control individuals to 22% in PSP patients (P<0.001). In young PSP patients, the H1B risk could be localized to a 22 kb regulatory region in intron 0 (P<0.001) and could be fully explained by one SNP, htSNP167, creating a LBP-1c/LSF/CP2 site, shown to regulate the expression of genes in other neurodegenerative disorders. Luciferase reporter data indicated that the 182 bp conserved regulatory region, in which htSNP167 is located, is transcriptionally active with both alleles differentially influencing expression. Further, we replicated the htSNP167 association in a second, independently ascertained US PSP patient-control sample. However, the htSNP association showed that H1 risk alone could not explain the overall differences in H1 and H2 frequencies in PSP patients and control individuals. Thus, risk variants on different H1 htSNP haplotypes and protective variants on H2 contribute to population risk for PSP.

Age Factors↗

PubMed2005

Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample.

We obtained conclusive linkage of Alzheimer disease (AD) with a candidate region of 19.7 cM at 7q36 in an extended multiplex family, family 1270, ascertained in a population-based study of early-onset AD in the northern Netherlands. Single-nucleotide polymorphism and haplotype association analyses of a Dutch patient-control sample further supported the linkage at 7q36. In addition, we identified a shared haplotype at 7q36 between family 1270 and three of six multiplex AD-affected families from the same geographical region, which is indicative of a founder effect and defines a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified one linked synonymous mutation, g.38030G-->C in exon 10, that affected codon 626 of the PAX transactivation domain interacting protein gene (PAXIP1). It remains to be determined whether PAXIP1 has a functional role in the expression of AD in family 1270 or whether another mutation at this locus explains the observed linkage and sharing. Together, our linkage data from the informative family 1270 and the association data in the population-based early-onset AD patient-control sample strongly support the identification of a novel AD locus at 7q36 and re-emphasize the genetic heterogeneity of AD.

Aged↗

PubMed2005

novoSNP, a novel computational tool for sequence variation discovery.

Technological improvements shifted sequencing from low-throughput, work-intensive, gel-based systems to high-throughput capillary systems. This resulted in a broad use of genomic resequencing to identify sequence variations in genes and regulatory, as well as extended genomic regions. We describe a software package, novoSNP, that conscientiously discovers single nucleotide polymorphisms (SNPs) and insertion-deletion polymorphisms (INDELs) in sequence trace files in a fast, reliable, and user-friendly way. We compared the performance of novoSNP with that of PolyPhred and PolyBayes on two data sets. The first data set comprised 1028 sequence trace files obtained from diagnostic mutation analyses of SCN1A (neuronal voltage-gated sodium channel alpha-subunit type I gene). The second data set comprised 9062 sequence trace files from a genomic resequencing project aiming at the construction of a high-density SNP map of MAPT (microtubule-associated protein tau gene). Visual inspection of these data sets had identified 38 sequence variations for SCN1A and 488 for MAPT. novoSNP automatically identified all 38 SCN1A variations including five INDELs, while for MAPT only 15 of the 488 variations were not correctly marked. PolyPhred detected far fewer SNPs as compared to novoSNP and missed nearly all INDELs. PolyBayes, designed for the sequence analysis of cloned templates, detected only a limited number of the variations present in the data set. Besides the significant improvement in the automated detection of sequence variations both in diagnostic mutation analyses and in SNP discovery projects, novoSNP also offers a user-friendly interface for inspecting possible genetic variations.

Animals↗

PubMed2004

SNPbox: a modular software package for large-scale primer design.

UNLABELLED: We developed a modular software package SNPbox that automates and standardizes the generation of PCR primers and is used in the strategy for constructing single nucleotide polymorphisms (SNPs) maps. In this strategy, the focus of primer design can be either on the validation of annotated public SNPs or on the SNP discovery in exon regions or extended genomic regions, both by resequencing. SNPbox relies on Primer3 for the primer design and combines this program with other publicly available software tools such as BLAST, Spidey and RepeatMasker, and newly developed algorithms. Primer conditions were chosen such that PCR amplifications are uniform for each PCR amplicon facilitating the use of high-throughput genetic platforms. SNPbox can also be used for the design of primer sets for mutation analysis, STR marker genotyping and microarray oligo design. Of the 2500 primer sets designed by SNPbox, 95% successfully amplified genomic DNA under uniform PCR conditions. AVAILABILITY: The software is available from the authors upon request. SUPPLEMENTARY INFORMATION: SNPbox_supplement.

Algorithms↗

PubMed2004

SNPbox: web-based high-throughput primer design from gene to genome.

SNPbox is a modular software package that automates the design of PCR primers for large-scale amplification and sequencing projects in a standardized manner resulting in high-quality PCR amplicons with a low failure rate. Here, we present the SNPbox web server at http://www.SNPbox.org, which hosts the SNPbox web service as well as the data from SNPbox analysis of all Ensembl exons. The data of this genome-wide SNPbox application can be visualized in Ensembl's ContigView through a DAS (distributed annotation system) annotation server.

DNA Primers↗

PubMed2004

SSHSuite: an integrated software package for analysis of large-scale suppression subtractive hybridization data.

Suppression subtractive hybridization (SSH) is a widely used technique for the identification of differentially expressed genes. SSH as well as other types of sequencing projects generate large amounts of anonymous sequences. SSHSuite automates the handling and storage of these sequences and enables identification through similarity searches. SSHSuite also offers analysis tools for the retrieval and comparison of the resulting similarity data. SSHSuite consists of four programs: SSHHandler, SSHOverview, SSHAnalysis, and SSHCompare.

Algorithms↗

PubMed2003

RnaViz 2: an improved representation of RNA secondary structure.

SUMMARY: RnaViz has been developed to easily create nice, publication quality drawings of RNA secondary structure. RnaViz 2 supports CT, DCSE, and RNAML input formats and improves on many aspects of the first version, notably portability and structure annotation. RnaViz is written using a hybrid programming approach combining pieces written in C and in the scripting language Tcl/Tk, making the program very portable and extensible. AVAILABILITY: Source code, binaries for Linux and MS Windows, and additional documentation are available athttp://rrna.uia.ac.be/rnaviz/

Base Sequence↗