Peter De Rijk

Publications (25)210 Total impact

• Article: Identification of rare copy number variants in high burden schizophrenia families.

  Maarten J Van Den Bossche, Mojca Strazisar, Sophia Cammaerts, Anthony M Liekens, Geert Vandeweyer, Veerle Depreeuw, Maria Mattheijssens, An-Sofie Lenaerts, Sonia De Zutter, Peter De Rijk, Bernard Sabbe, Jurgen Del-Favero
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  ABSTRACT: Over the last years, genome-wide studies consistently showed an increased burden of rare copy number variants (CNVs) in schizophrenia patients, supporting the "common disease, rare variant" hypothesis in at least a subset of patients. We hypothesize that in families with a high burden of disease, and thus probably a high genetic load influencing disease susceptibility, rare CNVs might be involved in the etiology of schizophrenia. We performed a genome-wide CNV analysis in the index patients of eight families with multiple schizophrenia affected members, and consecutively performed a detailed family analysis for the most relevant CNVs. One index patient showed a DRD5 containing duplication. A second index patient presented with an NRXN1 containing deletion and two adjacent duplications containing MYT1L and SNTG2. Detailed analysis in the subsequent families showed segregation of the identified CNVs. With this study we show the importance of screening high burden families for rare CNVs, which will not only broaden our knowledge concerning the molecular genetic mechanisms involved in schizophrenia but also allow the use of the obtained genetic data to provide better clinical care to these families in general and to non-symptomatic causal CNV carriers in particular. © 2013 Wiley Periodicals, Inc.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 03/2013; · 3.70 Impact Factor
• Source

  Available from: Zeliha Matur

  Dataset: Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia

  Magdalena Zimoń, Jonathan Baets, Leonardo Almeida-Souza, Els De Vriendt, Jelena Nikodinovic, Yesim Parman, Esra Battalo Gcaron Lu, Zeliha Matur, Velina Guergueltcheva, Ivailo Tournev, [......], Kristien Peeters, Tinne Ooms, Angelika F Hahn, Stephan Züchner, Vincent Timmerman, Patrick Van Dijck, Vedrana Milic Rasic, Andreas R Janecke, Peter De Jonghe, Albena Jordanova
• Source

  Available from: Zeliha Matur

  Article: Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.

  Magdalena Zimoń, Jonathan Baets, Leonardo Almeida-Souza, Els De Vriendt, Jelena Nikodinovic, Yesim Parman, Esra Battalo Gcaron Lu, Zeliha Matur, Velina Guergueltcheva, Ivailo Tournev, [......], Kristien Peeters, Tinne Ooms, Angelika F Hahn, Stephan Züchner, Vincent Timmerman, Patrick Van Dijck, Vedrana Milic Rasic, Andreas R Janecke, Peter De Jonghe, Albena Jordanova
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  ABSTRACT: Inherited peripheral neuropathies are frequent neuromuscular disorders known for their clinical and genetic heterogeneity. In 33 families, we identified 8 mutations in HINT1 (encoding histidine triad nucleotide-binding protein 1) by combining linkage analyses with next-generation sequencing and subsequent cohort screening of affected individuals. Our study provides evidence that loss of functional HINT1 protein results in a distinct phenotype of autosomal recessive axonal neuropathy with neuromyotonia.
  Nature Genetics 09/2012; 44(10):1080-3. · 35.53 Impact Factor
• Article: Less Cognitive and Neurological Deficits in Schizophrenia Patients Carrying Risk Variant in ZNF804A.

  Maarten J A Van Den Bossche, Lise Docx, Manuel Morrens, Sophia Cammaerts, Mojca Strazisar, Chris Bervoets, Stefanie Smolders, Veerle Depreeuw, An-Sofie Lenaerts, Peter De Rijk, Jurgen Del-Favero, Bernard G C Sabbe
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  ABSTRACT: Background: The rs1344706 single nucleotide polymorphism in the ZNF804A gene is a common variant with strong evidence for association with schizophrenia. Recent studies show an association of rs1344706 with cognitive functioning, and there is some evidence suggesting that the risk allele may increase susceptibility for a subtype of schizophrenia with relatively spared cognition. Methods: We tested the effect of rs1344706 genotype in 89 schizophrenia patients on 3 basic cognitive domains (working memory, processing speed and attention) shown to be severely impaired in schizophrenia. Also we investigated the effect of rs1344706 on the severity of neurological soft signs, subtle impairments in motor and sensory functions highly frequent in schizophrenia patients. Neurological soft signs and cognitive deficits are central features of schizophrenia and are tightly linked with clinical, social and functional outcome. Results: Our results show an association of higher rs1344706 risk allele load with improved performance on processing speed and with fewer neurological soft signs. Conclusions: Together with other studies, our findings suggest that ZNF804A is associated with a subtype of schizophrenia with better cognitive and neurological functioning. Discovery of the specific pathways through which ZNF804A is exerting this effect may lead to better prevention, diagnosis and treatment for a specific group of schizophrenia patients.
  Neuropsychobiology 08/2012; 66:158-66. · 2.67 Impact Factor
• Source

  Available from: Jurgen Del-Favero

  Article: Rare copy number variants in neuropsychiatric disorders: Specific phenotype or not?

  Maarten J Van Den Bossche, Mandy Johnstone, Mojca Strazisar, Benjamin S Pickard, Dirk Goossens, An-Sofie Lenaerts, Sonia De Zutter, Annelie Nordin, Karl-Fredrik Norrback, Julien Mendlewicz, Daniel Souery, Peter De Rijk, Bernard G Sabbe, Rolf Adolfsson, Douglas Blackwood, Jurgen Del-Favero
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  ABSTRACT: From a number of genome-wide association studies it was shown that de novo and/or rare copy number variants (CNVs) are found at an increased frequency in neuropsychiatric diseases. In this study we examined the prevalence of CNVs in six genomic regions (1q21.1, 2p16.3, 3q29, 15q11.2, 15q13.3, and 16p11.2) previously implicated in neuropsychiatric diseases. Hereto, a cohort of four neuropsychiatric disorders (schizophrenia, bipolar disorder, major depressive disorder, and intellectual disability) and control individuals from three different populations was used in combination with Multilpex Amplicon Quantifiaction (MAQ) assays, capable of high resolution (kb range) and custom-tailored CNV detection. Our results confirm the etiological candidacy of the six selected CNV regions for neuropsychiatric diseases. It is possible that CNVs in these regions can result in disturbed brain development and in this way lead to an increased susceptibility for different neuropsychiatric disorders, dependent on additional genetic and environmental factors. Our results also suggest that the neurodevelopmental component is larger in the etiology of schizophrenia and intellectual disability than in mood disorders. Finally, our data suggest that deletions are in general more pathogenic than duplications. Given the high frequency of the examined CNVs (1-2%) in patients of different neuropsychiatric disorders, screening of large cohorts with an affordable and feasible method like the MAQ assays used in this study is likely to result in important progress in unraveling the genetic factors leading to an increased susceptibility for several psychiatric disorders. © 2012 Wiley Periodicals, Inc.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 08/2012; 159B(7):812-22. · 3.70 Impact Factor
• Article: Identification of a CACNA2D4 deletion in late onset bipolar disorder patients and implications for the involvement of voltage-dependent calcium channels in psychiatric disorders.

  Maarten J Van Den Bossche, Mojca Strazisar, Stephan De Bruyne, Chris Bervoets, An-Sofie Lenaerts, Sonia De Zutter, Annelie Nordin, Karl-Fredrik Norrback, Dirk Goossens, Peter De Rijk, Elaine K Green, Detelina Grozeva, Julien Mendlewicz, Nick Craddock, Bernard G Sabbe, Rolf Adolfsson, Daniel Souery, Jurgen Del-Favero
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  ABSTRACT: The GWAS-based association of CACNA1C with bipolar disorder (BPD) is one of the strongest genetic findings to date. CACNA1C belongs to the family of CACN genes encoding voltage-dependent calcium channels (VDCCs). VDCCs are involved in brain circuits and cognitive processes implicated in BPD and schizophrenia (SZ). Recently, it was shown that rare copy number variations (CNVs) are found at an increased frequency in SZ and to a lesser extent also in BPD, suggesting the involvement of CNVs in the causation of these diseases. We hypothesize that CNVs in CACN genes can influence the susceptibility to BPD, SZ, and/or schizoaffective disorder (SZA). A search for CNVs in eight CACN genes in a patient-control sample of European decent was performed. A total of 709 BP patients, 645 SZ patients, 189 SZA patients, and 1,470 control individuals were screened using the Multiplex Amplicon Quantification (MAQ) method. We found a rare, partial deletion of 35.7 kb in CACNA2D4 in two unrelated late onset bipolar I patients and in one control individual. All three deletions shared the same breakpoints removing exons 17-26 of CACNA2D4, comprising part of the CACHE domain. Based on the data we cannot claim causality to BPD of the identified CACNA2D4 deletion but nevertheless this deletion can be important in unraveling the underlying processes leading to psychiatric diseases in general and BPD in particular.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 04/2012; 159B(4):465-75. · 3.70 Impact Factor
• Article: Optimized filtering reduces the error rate in detecting genomic variants by short-read sequencing.

  Joke Reumers, Peter De Rijk, Hui Zhao, Anthony Liekens, Dominiek Smeets, John Cleary, Peter Van Loo, Maarten Van Den Bossche, Kirsten Catthoor, Bernard Sabbe, Evelyn Despierre, Ignace Vergote, Brian Hilbush, Diether Lambrechts, Jurgen Del-Favero
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  ABSTRACT: Distinguishing single-nucleotide variants (SNVs) from errors in whole-genome sequences remains challenging. Here we describe a set of filters, together with a freely accessible software tool, that selectively reduce error rates and thereby facilitate variant detection in data from two short-read sequencing technologies, Complete Genomics and Illumina. By sequencing the nearly identical genomes from monozygotic twins and considering shared SNVs as 'true variants' and discordant SNVs as 'errors', we optimized thresholds for 12 individual filters and assessed which of the 1,048 filter combinations were effective in terms of sensitivity and specificity. Cumulative application of all effective filters reduced the error rate by 290-fold, facilitating the identification of genetic differences between monozygotic twins. We also applied an adapted, less stringent set of filters to reliably identify somatic mutations in a highly rearranged tumor and to identify variants in the NA19240 HapMap genome relative to a reference set of SNVs.
  Nature Biotechnology 12/2011; 30(1):61-8. · 29.50 Impact Factor
• Source

  Available from: Anthony Liekens

  Article: BioGraph: unsupervised biomedical knowledge discovery via automated hypothesis generation.

  Anthony M L Liekens, Jeroen De Knijf, Walter Daelemans, Bart Goethals, Peter De Rijk, Jurgen Del-Favero
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  ABSTRACT: We present BioGraph, a data integration and data mining platform for the exploration and discovery of biomedical information. The platform offers prioritizations of putative disease genes, supported by functional hypotheses. We show that BioGraph can retrospectively confirm recently discovered disease genes and identify potential susceptibility genes, outperforming existing technologies, without requiring prior domain knowledge. Additionally, BioGraph allows for generic biomedical applications beyond gene discovery. BioGraph is accessible at http://www.biograph.be.
  Genome biology 06/2011; 12(6):R57. · 6.63 Impact Factor
• Source

  Available from: Curt Tysk

  Article: Resequencing of positional candidates identifies low frequency IL23R coding variants protecting against inflammatory bowel disease.

  Yukihide Momozawa, Myriam Mni, Kayo Nakamura, Wouter Coppieters, Sven Almer, Leila Amininejad, Isabelle Cleynen, Jean-Frédéric Colombel, Peter de Rijk, Olivier Dewit, [......], Curt Tysk, Diana Zelenika, Mark Lathrop, Jurgen Del-Favero, Jean-Pierre Hugot, Martine de Vos, Denis Franchimont, Severine Vermeire, Edouard Louis, Michel Georges
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  ABSTRACT: Genome-wide association studies (GWAS) have identified dozens of risk loci for many complex disorders, including Crohn's disease. However, common disease-associated SNPs explain at most ∼20% of the genetic variance for Crohn's disease. Several factors may account for this unexplained heritability, including rare risk variants not adequately tagged thus far in GWAS. That rare susceptibility variants indeed contribute to variation in multifactorial phenotypes has been demonstrated for colorectal cancer, plasma high-density lipoprotein cholesterol levels, blood pressure, type 1 diabetes, hypertriglyceridemia and, in the case of Crohn's disease, for NOD2 (refs. 14,15). Here we describe the use of high-throughput resequencing of DNA pools to search for rare coding variants influencing susceptibility to Crohn's disease in 63 GWAS-identified positional candidate genes. We identify low frequency coding variants conferring protection against inflammatory bowel disease in IL23R, but we conclude that rare coding variants in positional candidates do not make a large contribution to inherited predisposition to Crohn's disease.
  Nature Genetics 01/2011; 43(1):43-7. · 35.53 Impact Factor
• Source

  Available from: Jurgen Del-Favero

  Article: Sequencing of DISC1 pathway genes reveals increased burden of rare missense variants in schizophrenia patients from a northern Swedish population.

  Lotte N Moens, Peter De Rijk, Joke Reumers, Maarten J A Van den Bossche, Wim Glassee, Sonia De Zutter, An-Sofie Lenaerts, Annelie Nordin, Lars-Göran Nilsson, Ignacio Medina Castello, Karl-Fredrik Norrback, Dirk Goossens, Kristel Van Steen, Rolf Adolfsson, Jurgen Del-Favero
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  ABSTRACT: In recent years, DISC1 has emerged as one of the most credible and best supported candidate genes for schizophrenia and related neuropsychiatric disorders. Furthermore, increasing evidence--both genetic and functional--indicates that many of its protein interaction partners are also involved in the development of these diseases. In this study, we applied a pooled sample 454 sequencing strategy, to explore the contribution of genetic variation in DISC1 and 10 of its interaction partners (ATF5, Grb2, FEZ1, LIS-1, PDE4B, NDE1, NDEL1, TRAF3IP1, YWHAE, and ZNF365) to schizophrenia susceptibility in an isolated northern Swedish population. Mutation burden analysis of the identified variants in a population of 486 SZ patients and 514 control individuals, revealed that non-synonymous rare variants with a MAF<0.01 were significantly more present in patients compared to controls (8.64% versus 4.7%, P = 0.018), providing further evidence for the involvement of DISC1 and some of its interaction partners in psychiatric disorders. This increased burden of rare missense variants was even more striking in a subgroup of early onset patients (12.9% versus 4.7%, P = 0.0004), highlighting the importance of studying subgroups of patients and identifying endophenotypes. Upon investigation of the potential functional effects associated with the identified missense variants, we found that ∼90% of these variants reside in intrinsically disordered protein regions. The observed increase in mutation burden in patients provides further support for the role of the DISC1 pathway in schizophrenia. Furthermore, this study presents the first evidence supporting the involvement of mutations within intrinsically disordered protein regions in the pathogenesis of psychiatric disorders. As many important biological functions depend directly on the disordered state, alteration of this disorder in key pathways may represent an intriguing new disease mechanism for schizophrenia and related neuropsychiatric diseases. Further research into this unexplored domain will be required to elucidate the role of the identified variants in schizophrenia etiology.
  PLoS ONE 01/2011; 6(8):e23450. · 4.09 Impact Factor
• Conference Proceeding: BioGraph: Knowledge Discovery and Exploration in the Biomedical Domain.

  Jeroen De Knijf, Anthony M. L. Liekens, Walter Daelemans, Peter De Rijk, Jurgen Del-Favero, Bart Goethals
  Data Mining Workshops (ICDMW), 2011 IEEE 11th International Conference on, Vancouver, BC, Canada, December 11, 2011; 01/2011
• Article: SCAMP5, NBEA and AMISYN: three candidate genes for autism involved in secretion of large dense-core vesicles.

  Dries Castermans, Karolien Volders, An Crepel, Liesbeth Backx, Rita De Vos, Kathleen Freson, Sandra Meulemans, Joris R Vermeesch, Connie T R M Schrander-Stumpel, Peter De Rijk, Jurgen Del-Favero, Chris Van Geet, Wim J M Van De Ven, Jean G Steyaert, Koen Devriendt, John W M Creemers
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  ABSTRACT: Autism is a neurodevelopmental disorder characterized by impaired social reciprocity, impaired communication and stereotypical behaviors. Despite strong evidence for a genetic basis, few susceptibility genes have been identified. Here, we describe the positional cloning of SCAMP5, CLIC4 and PPCDC as candidate genes for autism, starting from a person with idiopathic, sporadic autism carrying a de novo chromosomal translocation. One of these genes, SCAMP5 is silenced on the derivative chromosome, and encodes a brain-enriched protein involved in membrane trafficking, similar to the previously identified candidate genes NBEA and AMISYN. Gene silencing of Nbea, Amisyn and Scamp5 in mouse beta-TC3 cells resulted in a 2-fold increase in stimulated secretion of large dense-core vesicles (LDCVs), while overexpression suppressed secretion. Moreover, ultrastructural analysis of blood platelets from the patients with haploinsufficieny of one of the three candidate genes, showed morphological abnormalities of dense-core granules, which closely resemble LDCVs. Taken together, this study shows that in three independent patients with autism three different negative regulators of LDCV secretion are affected, respectively, suggesting that in at least a subgroup of patients the regulation of neuronal vesicle trafficking may be involved in the pathogenesis of autism.
  Human Molecular Genetics 04/2010; 19(7):1368-78. · 7.64 Impact Factor
• Article: Support for NRG1 as a susceptibility factor for schizophrenia in a northern Swedish isolated population.

  Maaike Alaerts, Shana Ceulemans, Diego Forero, Lotte N Moens, Sonia De Zutter, Lien Heyrman, An-Sofie Lenaerts, Karl-Fredrik Norrback, Peter De Rijk, Lars-Göran Nilsson, Dirk Goossens, Rolf Adolfsson, Jurgen Del-Favero
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  ABSTRACT: Neuregulin 1 (NRG1), a growth factor involved in neurodevelopment, myelination, neurotransmitter receptor expression, and synaptic plasticity, first joined the list of candidate genes for schizophrenia when a 7-marker haplotype at the 5' end of the gene (Hap(ICE)) was shown to be associated with the disorder in the Icelandic population. Since then, more genetic and functional evidence has emerged, which supports a role for NRG1 in the development of schizophrenia. To determine the contribution of NRG1 to susceptibility for schizophrenia in a northern Swedish isolated population. Detailed linkage disequilibrium (LD)-based patient-control association study. This is the first study to type and analyze the 7 Hap(ICE) markers and a set of 32 HapMap tagging single-nucleotide polymorphisms (SNPs) that represents variants with a minor allele frequency of at least 1% and fully characterizes the LD structure of the 5' part of NRG1. Outpatient and inpatient hospitals. A total of 486 unrelated patients with schizophrenia and 514 unrelated control individuals recruited from a northern Swedish isolated population. Association between markers and disease. Analysis of the Hap(ICE) markers showed the association of a 7-marker and 2-microsatellite haplotype, different from the haplotypes associated in the Icelandic population and overrepresented in northern Swedish control individuals. Subsequently, a more detailed analysis that included all 37 genotyped SNPs was performed by investigating haplotypic association, dependent and independent of LD block structure. We found significant association with 5 SNPs located in the second intron of NRG1 (.007 </= P </= .04). Also, 2-, 3-, and 4-SNP windows that comprise these SNPs were associated (P < 3 x 10(-4)). One protective haplotype (0% vs 1.8%; P <5 x 10(-5)) and 1 disease risk-causing haplotype (40.4% vs 34.9%, P = .02) were defined. The NRG1 gene contributes to the susceptibility for schizophrenia in the northern Swedish population.
  Archives of general psychiatry 09/2009; 66(8):828-37. · 12.26 Impact Factor
• Source

  Available from: Jurgen Del-Favero

  Article: Simultaneous mutation and copy number variation (CNV) detection by multiplex PCR-based GS-FLX sequencing.

  Dirk Goossens, Lotte N Moens, Eva Nelis, An-Sofie Lenaerts, Wim Glassee, Andreas Kalbe, Bruno Frey, Guido Kopal, Peter De Jonghe, Peter De Rijk, Jurgen Del-Favero
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  ABSTRACT: We evaluated multiplex PCR amplification as a front-end for high-throughput sequencing, to widen the applicability of massive parallel sequencers for the detailed analysis of complex genomes. Using multiplex PCR reactions, we sequenced the complete coding regions of seven genes implicated in peripheral neuropathies in 40 individuals on a GS-FLX genome sequencer (Roche). The resulting dataset showed highly specific and uniform amplification. Comparison of the GS-FLX sequencing data with the dataset generated by Sanger sequencing confirmed the detection of all variants present and proved the sensitivity of the method for mutation detection. In addition, we showed that we could exploit the multiplexed PCR amplicons to determine individual copy number variation (CNV), increasing the spectrum of detected variations to both genetic and genomic variants. We conclude that our straightforward procedure substantially expands the applicability of the massive parallel sequencers for sequencing projects of a moderate number of amplicons (50-500) with typical applications in resequencing exons in positional or functional candidate regions and molecular genetic diagnostics.
  Human Mutation 01/2009; 30(3):472-6. · 5.69 Impact Factor
• Article: Detailed analysis of the serotonin transporter gene (SLC6A4) shows no association with bipolar disorder in the Northern Swedish population.

  Maaike Alaerts, Shana Ceulemans, Diego Forero, Lotte N Moens, Sonia De Zutter, Lien Heyrman, An-Sofie Lenaerts, Karl-Fredrik Norrback, Dirk Goossens, Peter De Rijk, Lars-Göran Nilsson, Rolf Adolfsson, Jurgen Del-Favero
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  ABSTRACT: Through active reuptake of serotonin into presynaptic neurons, the serotonin transporter (5-HTT) plays an important role in regulating serotonin concentrations in the brain, and it is the site of binding for tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Therefore it has been hypothesized that this transporter is involved in the etiology of bipolar (BP) disorder. Inconsistent association study results for the SLC6A4 gene encoding 5-HTT reported in literature emphasize the need for more systematic and detailed analyses of this candidate gene. We performed an extensive analysis of SLC6A4 on DNA of 254 BPI patients and 364 control individuals from a Northern Swedish isolated population. This analysis consisted of a HapMap LD-based association study including three widely investigated polymorphisms (5-HTTVNTR, 5-HTTLPR, and rs3813034), a copy-number variation (CNV) analysis and a mutation analysis of the complete coding sequence and the 3'-UTR of SLC6A4. No single marker showed statistically significant association with BPI, nor did any of the haplotypes. In the mutation analysis 13 novel variants were detected, including 2 amino acid substitutions M389V and I587L, but these are probably not implicated in risk for BP. No deletions or duplications were detected in the CNV analysis. We conclude that variation in the SLC6A4 gene or its regulatory regions does not contribute to the susceptibility for BP disorder in the Northern Swedish population.
  American Journal of Medical Genetics Part B Neuropsychiatric Genetics 10/2008; 150B(4):585-92. · 3.70 Impact Factor
• Article: novoSNP3: variant detection and sequence annotation in resequencing projects.

  Peter De Rijk, Jurgen Del-Favero
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  ABSTRACT: The same high-throughput techniques used to make genomic sequences generally available, are also useful in mapping the genetic differences between individuals. Resequencing of a genomic region in a set of individuals is considered the golden standard for the discovery of sequence variants. However, with the available high-throughput sequencing technology data analysis has become the rate-limiting step in data management and analysis of large resequencing projects. To solve this issue we developed a software package novoSNP that conscientiously discovers single nucleotide polymorphisms and insertion-deletion polymorphisms in sequence trace files in a fast, reliable and user friendly way. Furthermore, it can also be used to create databases containing annotated reference sequences, add and align trace data, keep track of validation status of variants, annotate variants, and produce reports on validated variants and genotypes. novoSNP is available from http://www.molgen.ua.ac.be/bioinfo/novosnp. There are versions for MS Windows as well as Linux.
  Methods in molecular biology (Clifton, N.J.) 02/2007; 396:331-44.
• Article: SNPbox : Web-Based High-Throughput Primer Design with an Eye for Repetitive Sequences.

  Stefan Weckx, Peter De Rijk, Wim Glassee, Christine Van Broeckhoven, Jurgen Del-Favero
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  ABSTRACT: In this omics era, researchers in biosciences need more than ever user-friendly, fast, and straightforward computational tools for high-throughput research. In this chapter, we present SNPbox and explain the general primer design strategy. We also show how the four modules, Exon, Single-Nucleotide Polymorphism (SNP), Saturation, and Exon + Saturation, exactly apply the primer design strategy, give clear guidance for users of the Web interface at http://www.SNPbox.org, and explain how pre-designed primers for Ensembl genes can be visualized and retrieved.
  Methods in molecular biology (Clifton, N.J.) 01/2007; 402:178-199.
• Chapter: novoSNP3

  Peter De Rijk, Jurgen Del-Favero
  [show abstract] [hide abstract]
  ABSTRACT: The same high-throughput techniques used to make genomic sequences generally available, are also useful in mapping the genetic differences between individuals. Resequencing of a genomic region in a set of individuals is considered the golden standard for the discovery of sequence variants. However, with the available high-throughput sequencing technology data analysis has become the rate-limiting step in data management and analysis of large resequencing projects. To solve this issue we developed a software package novoSNP that conscientiously discovers single nucleotide polymorphisms and insertion-deletion polymorphisms in sequence trace files in a fast, reliable and user friendly way. Furthermore, it can also be used to create databases containing annotated reference sequences, add and align trace data, keep track of validation status of variants, annotate variants, and produce reports on validated variants and genotypes. novoSNP is available from http://www.molgen.ua.ac.be/bioinfo/novosnp. There are versions for MS Windows as well as Linux Key WordsSNP detection–insertion/deletion detection–resequencing–DNA sequence analysis–genetic variant–high-throughput analysis–automation
  12/2006: pages 331-344;
• Article: High-density SNP haplotyping suggests altered regulation of tau gene expression in progressive supranuclear palsy.

  Rosa Rademakers, Stacey Melquist, Marc Cruts, Jessie Theuns, Jurgen Del-Favero, Parvoneh Poorkaj, Matt Baker, Kristel Sleegers, Richard Crook, Tim De Pooter, [......], Natalie Thomas, Sebastiaan Engelborghs, Michael Heckman, Irene Litvan, Julia Crook, Peter P De Deyn, Dennis Dickson, Gerard D Schellenberg, Christine Van Broeckhoven, Michael L Hutton
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  ABSTRACT: 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.
  Human Molecular Genetics 11/2005; 14(21):3281-92. · 7.64 Impact Factor
• Article: Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample.

  Rosa Rademakers, Marc Cruts, Kristel Sleegers, Bart Dermaut, Jessie Theuns, Yurii Aulchenko, Stefan Weckx, Tim De Pooter, Marleen Van den Broeck, Ellen Corsmit, Peter De Rijk, Jurgen Del-Favero, John van Swieten, Cornelia M van Duijn, Christine Van Broeckhoven
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  ABSTRACT: 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.
  The American Journal of Human Genetics 10/2005; 77(4):643-52. · 10.60 Impact Factor