Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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    Identification of species-specific novel transcripts in pig reproductive tissues using RNA-seq
    Du, Z. ; Eisley, C.J. ; Onteru, S.K. ; Madsen, O. ; Groenen, M. ; Ross, J.W. ; Rothschild, M.F. - \ 2014
    Animal Genetics 45 (2014)2. - ISSN 0268-9146 - p. 198 - 204.
    long noncoding rnas - extreme phenotypes - human genome - litter size - disease - mechanisms - evolution - discovery - reveals - mir-675
    Although structural properties of the porcine reproductive system are shared by many placental mammals, some combination of these properties is unique to pigs. To explore whether genomic elements specific to pigs could potentially underlie this uniqueness, we made the first step to identify novel transcripts in two representative pig reproductive tissues by the technique of massively parallel sequencing. To automate the whole process, we built a computational pipeline, which can also be easily extended for similar studies in other species. In total, 5516 and 9061 novel transcripts were found, and 159 and 252 novel transcripts appear to be specific to pigs for the placenta and testis respectively. Furthermore, these novel transcripts were found to be enriched in quantitative trait loci (QTL) regions for reproduction traits in pigs. We validated eight of these novel transcripts by quantitative real-time PCR. With respect to their genomic organization and their functional relationship to reproduction, these transcripts need to be further validated and explored in various pig breeds to better comprehend the relevant aspects of pig physiology that contribute to reproductive performance.
    Common and rare single nucleotide polymorphisms in the LDLR gene are present in a black South African population and associate with low-density lipoprotein cholesterol levels
    Zyl, T. ; Jerling, J.C. ; Conradie, K.R. ; Feskens, E.J.M. - \ 2014
    Journal of Human Genetics 59 (2014). - ISSN 1434-5161 - p. 88 - 94.
    coronary-heart-disease - plasma-lipid levels - receptor gene - familial hypercholesterolemia - messenger-rna - human genome - mutations - risk - stabilization - expression
    The LDL receptor has an essential role in regulating plasma LDL-C levels. Genetic variation in the LDLR gene can be associated with either lower or moderately raised plasma levels of LDL-C, or may cause familial hypercholesterolemia. The prevalence of single-nucleotide polymorphisms (SNPs) in the LDLR in the black South African population is not known and therefore, we aimed to determine the genotypic variation of the LDLR in the study population as well as to define the association of the different genotypes with plasma LDL-C levels. A random selection of 1860 apparently healthy black South African volunteers aged 35–60 years was made in a cross-sectional study. Novel SNPs were identified in a subset of 30 individuals by means of automated sequencing before screening the entire cohort by means of the Illumina VeraCode GoldenGate Genotyping Assay on a BeadXpress Reader system. Twenty-five SNPs were genotyped, two of which were novel. A very rare SNP, rs17249141, in the promoter region was significantly associated with lower levels of LDL-C. Four other SNPs (rs2738447, rs14158, rs2738465 and rs3180023) were significantly associated with increased levels of LDL-C. We can conclude that some of the various SNPs identified do indeed associate with LDL-C levels
    Large scale variation in DNA copy number in chicken breeds
    Crooijmans, R.P.M.A. ; Fife, M. ; FitzGerald, R.J. ; strickland, S. ; Groenen, M. - \ 2013
    BMC Genomics 14 (2013). - ISSN 1471-2164
    human genome - structural variation - mareks-disease - evolution - map - genes - resistance - feather - loci - pcr
    Background Detecting genetic variation is a critical step in elucidating the molecular mechanisms underlying phenotypic diversity. Until recently, such detection has mostly focused on single nucleotide polymorphisms (SNPs) because of the ease in screening complete genomes. Another type of variant, copy number variation (CNV), is emerging as a significant contributor to phenotypic variation in many species. Here we describe a genome-wide CNV study using array comparative genomic hybridization (aCGH) in a wide variety of chicken breeds. Results We identified 3,154 CNVs, grouped into 1,556 CNV regions (CNVRs). Thirty percent of the CNVs were detected in at least 2 individuals. The average size of the CNVs detected was 46.3 kb with the largest CNV, located on GGAZ, being 4.3 Mb. Approximately 75% of the CNVs are copy number losses relatively to the Red Jungle Fowl reference genome. The genome coverage of CNVRs in this study is 60 Mb, which represents almost 5.4% of the chicken genome. In particular large gene families such as the keratin gene family and the MHC show extensive CNV. Conclusions A relative large group of the CNVs are line-specific, several of which were previously shown to be related to the causative mutation for a number of phenotypic variants. The chance that inter-specific CNVs fall into CNVRs detected in chicken is related to the evolutionary distance between the species. Our results provide a valuable resource for the study of genetic and phenotypic variation in this phenotypically diverse species.
    An atlas of over 90.000 conserved noncoding sequences provides insight into crucifer regulatory regions
    Haudry, A. ; Platts, A.E. ; Vello, E. ; Hoen, D.R. ; Leclerq, M. ; Williamson, R.J. ; Forczek, E. ; Joly-Lopez, Z. ; Steffen, J.G. ; Hazzouri, K.M. ; Dewar, K. ; Stinchcombe, J.R. ; Schoen, D.J. ; Wang, X. ; Schmutz, J. ; Town, C.D. ; Edger, P.P. ; Pires, J.C. ; Schumaker, K.S. ; Jarvis, D.E. ; Mandakova, T. ; Lysak, M. ; Bergh, E. van den; Schranz, M.E. ; Harrison, P.M. - \ 2013
    Nature Genetics 45 (2013). - ISSN 1061-4036 - p. 891 - 898.
    arabidopsis-thaliana - human genome - dna elements - ultraconserved elements - brassica-oleracea - gene-expression - evolution - drosophila - size - annotation
    Despite the central importance of noncoding DNA to gene regulation and evolution, understanding of the extent of selection on plant noncoding DNA remains limited compared to that of other organisms. Here we report sequencing of genomes from three Brassicaceae species (Leavenworthia alabamica, Sisymbrium irio and Aethionema arabicum) and their joint analysis with six previously sequenced crucifer genomes. Conservation across orthologous bases suggests that at least 17% of the Arabidopsis thaliana genome is under selection, with nearly one-quarter of the sequence under selection lying outside of coding regions. Much of this sequence can be localized to approximately 90,000 conserved noncoding sequences (CNSs) that show evidence of transcriptional and post-transcriptional regulation. Population genomics analyses of two crucifer species, A. thaliana and Capsella grandiflora, confirm that most of the identified CNSs are evolving under medium to strong purifying selection. Overall, these CNSs highlight both similarities and several key differences between the regulatory DNA of plants and other species.
    Balancing of Histone H3K4 Methylation States by the Kdm5c/SMCX Histone Demethylase Modulates Promoter and Enhancer Function
    Outchkourov, N.S. ; Muino Acuna, J.M. ; Kaufmann, K. ; IJken, W.F.J. ; Groot Koerkamp, M.J. ; Leenen, D. van; Graaf, P. de; Holstege, F.C.P. ; Grosveld, F. ; Timmers, H.T.M. - \ 2013
    Cell Reports 3 (2013)4. - ISSN 2211-1247 - p. 1071 - 1079.
    little-imaginal-discs - embryonic stem-cells - binding-protein 2 - gene-expression - distinct functions - self-renewal - human genome - transcription - differentiation - reveals
    The functional organization of eukaryotic genomes correlates with specific patterns of histone methylations. Regulatory regions in genomes such as enhancers and promoters differ in their extent of methylation of histone H3 at lysine-4 (H3K4), but it is largely unknown how the different methylation states are specified and controlled. Here, we show that the Kdm5c/Jarid1c/SMCX member of the Kdm5 family of H3K4 demethylases can be recruited to both enhancer and promoter elements in mouse embryonic stem cells and in neuronal progenitor cells. Knockdown of Kdm5c deregulates transcription via local increases in H3K4me3. Our data indicate that by restricting H3K4me3 modification at core promoters, Kdm5c dampens transcription, but at enhancers Kdm5c stimulates their activity. Remarkably, an impaired enhancer function activates the intrinsic promoter activity of Kdm5c-bound distal elements. Our results demonstrate that the Kdm5c demethylase plays a crucial and dynamic role in the functional discrimination between enhancers and core promoters
    Prediction of a deletion copy number variant by a dense SNP panel
    Kadri, N.K. ; Koks, P.D. ; Meuwissen, T.H.E. - \ 2012
    Genetics, Selection, Evolution 44 (2012). - ISSN 0999-193X
    human genome - linkage disequilibrium - cattle - maps
    Background: A newly recognized type of genetic variation, Copy Number Variation (CNV), is detected in mammalian genomes, e.g. the cattle genome. This form of variation can potentially cause phenotypic variation. Our objective was to determine whether dense SNP (single nucleotide polymorphisms) panels can capture the genetic variation due to a simple bi-allelic CNV, with the prospect of including the effect of such structural variations into genomic predictions. Methods: A deletion type CNV on bovine chromosome 6 was predicted from its neighboring SNP with a multiple regression model. Our dataset consisted of CNV genotypes of 1,682 cows, along with 100 surrounding SNP genotypes. A prediction model was fitted considering 10 to 100 surrounding SNP and the accuracy obtained directly from the model was confirmed by cross-validation. Results and conclusions: The accuracy of prediction increased with an increasing number of SNP in the model and the predicted accuracies were similar to those obtained by cross-validation. A substantial increase in accuracy was observed when the number of SNP increased from 10 to 50 but thereafter the increase was smaller, reaching the highest accuracy (0.94) with 100 surrounding SNP. Thus, we conclude that the genotype of a deletion type CNV and its putative QTL effect can be predicted with a maximum accuracy of 0.94 from surrounding SNP. This high prediction accuracy suggests that genetic variation due to simple deletion CNV is well captured by dense SNP panels. Since genomic selection relies on the availability of a dense marker panel with markers in close linkage disequilibrium to the QTL in order to predict their genetic values, we also discuss opportunities for genomic selection to predict the effects of CNV by dense SNP panels, when CNV cause variation in quantitative traits.
    Including copy number variation in association studies to predict genotypic values
    Calus, M.P.L. ; Koning, de, D.J. ; Haley, C.S. - \ 2010
    Genetics Research 92 (2010)2. - ISSN 0016-6723 - p. 115 - 125.
    wide linkage disequilibrium - human genome - mutation-rates - genetic risk - disease - polymorphism - markers - cattle - snps - microsatellite
    The objective of this study was to investigate, both empirically and deterministically, the ability to explain genetic variation resulting from a copy number polymorphism (CNP) by including the CNP, either by its genotype or by a continuous derivation thereof, alone or together with a nearby single nucleotide polymorphism (SNP) in the model. This continuous measure of a CNP genotype could be a raw hybridization measurement, or a predicted CNP genotype. Results from simulations showed that the linkage disequilibrium (LD) between an SNP and CNP was lower than LD between two SNPs, due to the higher mutation rate at the CNP loci. The model R2 values from analysing the simulated data were very similar to the R2 values predicted with the deterministic formulae. Under the assumption that x copies at a CNP locus lead to the effect of x times the effect of 1 copy, including a continuous measure of a CNP locus in the model together with the genotype of a nearby SNP increased power to explain variation at the CNP locus, even when the continuous measure explained only 15% of the variation at the CNP locus.
    Comparison of linkage disequilibrium and haplotype diversity on macro- and microchromosomes in chicken
    Megens, H.J.W.C. ; Crooijmans, R.P.M.A. ; Bastiaansen, J.W.M. ; Kerstens, H.H.D. ; Coster, A. ; Jalving, R. ; Vereijken, A. ; Silva, P. da; Muir, W.M. ; Cheng, H.H. ; Hanotte, O. ; Groenen, M.A.M. - \ 2009
    BMC Genetics 10 (2009). - ISSN 1471-2156 - 11 p.
    effective population-size - human genome - snps - map - biodiversity - evolution - sequence - breeds - extent
    Background: The chicken (Gallus gallus), like most avian species, has a very distinct karyotype consisting of many micro-and a few macrochromosomes. While it is known that recombination frequencies are much higher for micro-as compared to macrochromosomes, there is limited information on differences in linkage disequilibrium (LD) and haplotype diversity between these two classes of chromosomes. In this study, LD and haplotype diversity were systematically characterized in 371 birds from eight chicken populations (commercial lines, fancy breeds, and red jungle fowl) across macro-and microchromosomes. To this end we sampled four regions of similar to 1 cM each on macrochromosomes (GGA1 and GGA2), and four 1.5 -2 cM regions on microchromosomes (GGA26 and GGA27) at a high density of 1 SNP every 2 kb (total of 889 SNPs). Results: At a similar physical distance, LD, haplotype homozygosity, haploblock structure, and haplotype sharing were all lower for the micro-as compared to the macrochromosomes. These differences were consistent across populations. Heterozygosity, genetic differentiation, and derived allele frequencies were also higher for the microchromosomes. Differences in LD, haplotype variation, and haplotype sharing between populations were largely in line with known demographic history of the commercial chicken. Despite very low levels of LD, as measured by r(2) for most populations, some haploblock structure was observed, particularly in the macrochromosomes, but the haploblock sizes were typically less than 10 kb. Conclusion: Differences in LD between micro- and macrochromosomes were almost completely explained by differences in recombination rate. Differences in haplotype diversity and haplotype sharing between micro- and macrochromosomes were explained by differences in recombination rate and genotype variation. Haploblock structure was consistent with demography of the chicken populations, and differences in recombination rates between micro- and macrochromosomes. The limited haploblock structure and LD suggests that future whole-genome marker assays will need 100+K SNPs to exploit haplotype information. Interpretation and transferability of genetic parameters will need to take into account the size of chromosomes in chicken, and, since most birds have microchromosomes, in other avian species as well
    Bioactive compounds: Safety and efficacy (Consensus Meeting - Part II)
    Biesalski, H.K. ; Dragsted, L.O. ; Elmadfa, I. ; Grossklaus, R. ; Müller, M.R. ; Schrenk, D. ; Walter, P. ; Weber, P. - \ 2009
    Nutrition 25 (2009)11-12. - ISSN 0899-9007 - p. 1206 - 1211.
    single-nucleotide polymorphisms - human genome - receptors - sequence - disease - diet
    The efficacy and safety of bioactive compounds depend on a few known and unknown parameters. What is a physiologic dose and how can that dose be defined in cases of bioactive compounds with a poor knowledge of supply and distribution? What safety sets are needed? How can individual aspects such as polymorphisms or differences in absorption be considered? A group of experts tried to answer these and related questions during the 23rd Hohenheim Consensus Meeting at the University of Hohenheim in Stuttgart. (C) 2009 Elsevier Inc. All rights reserved.
    Consumer acceptance of nutrigenomics based personalised nutrition
    Ronteltap, A. ; Trijp, J.C.M. van; Renes, R.J. - \ 2009
    The British journal of nutrition 101 (2009)1. - ISSN 0007-1145 - p. 132 - 144.
    conjoint-analysis - human genome - health - foods - preference - information - technology - ambiguity - conflict - products
    Nutrigenomics is a new and promising development in nutritional science which aims to understand the fundamental molecular processes affected by foods. Despite general agreement on its promise for better understanding diet¿health relationships, less consensus exists among experts on the potential of spin-offs aimed at the consumer such as personalised nutrition. Research into consumer acceptance of such applications is scarce. The present study develops a set of key hypotheses on public acceptance of personalised nutrition and tests these in a representative sample of Dutch consumers. An innovative consumer research methodology is used in which consumers evaluate short films which are systematically varied scenarios for the future of personalised nutrition. Consumer evaluations of these films, which are pre-tested in a pilot study, allow a formal test of how consumer perceptions of personalised nutrition drive consumer acceptance and through which fundamental psychological processes these effects are mediated. Public acceptance is enhanced if consumers can make their genetic profile available free at their own choice, if the actual spin-off products provide a clearly recognisable advantage to the consumer, and are easy to implement into the daily routine. Consumers prefer communication on nutrigenomics and personalised nutrition by expert stakeholders to be univocal and aimed at building support with consumers and their direct environments for this intriguing new development. Additionally, an exploratory segmentation analysis indicated that people have different focal points in their preferences for alternative scenarios of personalised nutrition. The insights obtained from the present study provide guidance for the successful further development of nutrigenomics and its applications.
    Linkage Disequilibrium Decay and Haplotype Block Structure in the Pig
    Amaral, A.J. ; Megens, H.J.W.C. ; Crooijmans, R.P.M.A. ; Heuven, H.C.M. ; Groenen, M.A.M. - \ 2008
    Genetics 179 (2008)1. - ISSN 0016-6731 - p. 569 - 579.
    human genome - microsatellite markers - disease genes - sus-scrofa - domestication - breeds - populations - diversity - extent - map
    Linkage disequilibrium (LD) may reveal much about domestication and breed history. Ail investigation was conducted, to analyze the extent of LD, haploblock partitioning, and haplotype diversity within haploblocks across several pig breeds from China and Europe and in European wild boar. In total, 371 single-nucleotide-polymorph isms located in three genomic regions were genotyped. The extent of LD differed significantly between European and Chinese breeds, extending tip to 2 cM in Europe and up to 0.05 cM in China. In European breeds, LD extended over large haploblocks tip to 400 kb, whereas in Chinese breeds the extent of LD was smaller and generally did not exceed 10 kb. The European wild boar showed an intermediate level of LD between Chinese and European breeds. In Europe, the extent of LD also differed according to genomic region. Chinese breeds showed a higher level of haplotype diversity and shared high levels of frequent haplotypes with Large White, Landrace, and Duroc. The extent of LD differs between both centers of pig domestication, being higher in Europe. Two hypotheses can explain these findings. First, the European ancestral stock had a higher level of LD. Second, modern breeding programs increased the extent of LD in Europe and caused differences of LD between genomic regions. Large White, Landrace, and Duroc showed evidence of past introgression from Chinese breeds.
    Extent of linkage disequilibrium in chicken
    Aerts, J. ; Megens, H.J.W.C. ; Veenendaal, T. ; Ovcharenko, I. ; Crooijmans, R.P.M.A. ; Gordon, L. ; Stubbs, L. ; Groenen, M.A.M. ; Rodoinov, A. ; Gaginskaya, E. - \ 2007
    Cytogenetic and Genome Research 117 (2007). - ISSN 1424-8581 - p. 338 - 345.
    human genome - map - populations - patterns - sequence - regions - traits - cattle
    Many of the economically important traits in chicken are multifactorial and governed by multiple genes located at different quantitative trait loci (QTLs). The optimal marker density to identify these QTLs in linkage and association studies is largely determined by the extent of linkage disequilibrium (LD) around them. In this study, we investigated the extent of LD on two chromosomes in a white layer and two broiler chicken breeds. Pairwise levels of LD were calculated for 33 and 36 markers on chromosomes 10 and 28, respectively. We found that useful LD (i.e. an r2 value higher than 0.3) in Nutreco chicken breed E5 (inbred) can extend to around 1 cM on chromosomes 10 and 28, although in a second region on chromosome 28 it extends to about 2.5 cM. The extent in breed Nutreco E3 (outbred) was very short in chromosome 10 (15 kb) but very much larger on chromosome 28, particularly in one region of depressed heterozygosity. The layer breed E2 (inbred) showed an extent of useful LD up to 4 cM on chromosome 10; the extent on chromosome 28 could not be assessed due to an erratic pattern of LD on that chromosome, although in one region LD appears to be in the order of 0.8 cM. This indicates that there may be very large differences in patterns of LD between different chicken breeds and different genomic regions.
    Marker densities and the mapping of ancestral junctions
    Macleod, A.K. ; Haley, C.S. ; Woolliams, J.A. ; Stam, P. - \ 2005
    Genetical Research 85 (2005)1. - ISSN 0016-6723 - p. 69 - 79.
    random mating populations - linkage disequilibrium - haplotype blocks - human genome - recombination - segments - descent - model
    In any partially inbred population, `junctions` are the loci that form boundaries between segments of ancestral chromosomes. Here we show that the expected number of junctions per Morgan in such a population is linearly related to the inbreeding coefficient of the population, with a maximum in a completely inbred population corresponding to the prediction given by Stam (1980). We further show that high-density marker maps (fully informative markers with average densities of up to 200 per cM) will fail to detect a significant proportion of the junctions present in highly inbred populations. The number of junctions detected is lower than that which would be expected if junctions were distributed randomly along the chromosome, and we show that junctions are not, in fact randomly spaced. This non-random spacing of junctions significantly increases the number of markers that is required to detect 90% of the junctions present on any chromosome: a marker count of at least 12 times the number of junctions present will be needed to detect this proportion
    A high-resolution radiation hybrid map of chicken chromosome 5 and comparison with human chromosomes
    Pitel, F. ; Abasht, B. ; Morrison, M. ; Crooijmans, R.P.M.A. ; Vignoles, F. ; Leroux, S. ; Feve, K. ; Bardes, S. ; Milan, D. ; Lagarrigue, S. ; Groenen, M.A.M. ; Douaire, M. ; Vignal, A. - \ 2004
    BMC Genomics 5 (2004). - ISSN 1471-2164 - 9 p.
    in-situ hybridization - human genome - genes - assignment - sequences - synteny - panel - pig
    Background - The resolution of radiation hybrid (RH) maps is intermediate between that of the genetic and BAC (Bacterial Artificial Chromosome) contig maps. Moreover, once framework RH maps of a genome have been constructed, a quick location of markers by simple PCR on the RH panel is possible. The chicken ChickRH6 panel recently produced was used here to construct a high resolution RH map of chicken GGA5. To confirm the validity of the map and to provide valuable comparative mapping information, both markers from the genetic map and a high number of ESTs (Expressed Sequence Tags) were used. Finally, this RH map was used for testing the accuracy of the chicken genome assembly for chromosome 5. Results - A total of 169 markers (21 microsatellites and 148 ESTs) were typed on the ChickRH6 RH panel, of which 134 were assigned to GGA5. The final map is composed of 73 framework markers extending over a 1315.6 cR distance. The remaining 61 markers were placed alongside the framework markers within confidence intervals. Conclusion - The high resolution framework map obtained in this study has markers covering the entire chicken chromosome 5 and reveals the existence of a high number of rearrangements when compared to the human genome. Only two discrepancies were observed in relation to the sequence assembly recently reported for this chromosome.
    Development of a single nucleotide polymorphism map of porcine chromosome 2
    Jungerius, B.J. ; Rattink, A.P. ; Crooijmans, R.P.M.A. ; Poel, J.J. van der; Oost, B.A. van; Pas, M.F.W. te; Groenen, M.A.M. - \ 2003
    Animal Genetics 34 (2003)6. - ISSN 0268-9146 - p. 429 - 437.
    dna-sequence diversity - human genome - sus scrofa - pigs - identification - discovery - genes - loci
    Single nucleotide polymorphism markers are developed on SSC2, predominantly on the p-arm. Several studies reported a quantitative trait loci (QTL) for backfat thickness in this region. Single nucleotide polymorphisms were identified by comparative re-sequencing of polymerase chain reaction (PCR) products from a panel of eight individuals. The panel consisted of five Large Whites (each from a different Dutch breeding company), a Meishan, a Pietrain and a Wild Boar. In total, 67 different PCR products were sequenced and 301 SNPs were identified in 32 429 bp of consensus sequence, an average of one SNP in every 108 bp. After correction for sample size, this polymorphism rate corresponds to a heterozygosity value of one SNP in every 357 bp. For 63% of the SNPs, there was variation among the five Large Whites, and these SNPs are relevant for linkage and association studies in commercial populations. Comparing the Whites with other breeds revealed higher variation rates with: (i) Meishan, 89%; (ii) Pietrain, 69%; (iii) Wild Boar, 70%. Because many of the experimental populations to identify QTL are based on crosses between these breeds, these SNPs are relevant for the fine mapping of the QTL identified within these crosses.
    A new web-based data mining tool for the identification of candidate genes for human genetic disorders
    Driel, M.A. van; Cuelenaere, K. ; Kemmeren, P.P.C.W. ; Leunissen, J.A.M. ; Brunner, H.G. - \ 2003
    European Journal of Human Genetics 11 (2003). - ISSN 1018-4813 - p. 57 - 63.
    recessive robinow-syndrome - human genome - expression database - noonan-syndrome - adult-syndrome - sequence - mutation - dysplasia - mouse - ror2
    To identify the gene underlying a human genetic disorder can be difficult and time-consuming. Typically, positional data delimit a chromosomal region that contains between 20 and 200 genes. The choice then lies between sequencing large numbers of genes, or setting priorities by combining positional data with available expression and phenotype data, contained in different internet databases. This process of examining positional candidates for possible functional clues may be performed in many different ways, depending on the investigator's knowledge and experience. Here, we report on a new tool called the GeneSeeker, which gathers and combines positional data and expression/phenotypic data in an automated way from nine different web-based databases. This results in a quick overview of interesting candidate genes in the region of interest. The GeneSeeker system is built in a modular fashion allowing for easy addition or removal of databases if required. Databases are searched directly through the web, which obviates the need for data warehousing. In order to evaluate the GeneSeeker tool, we analysed syndromes with known genesis. For each of 10 syndromes the GeneSeeker programme generated a shortlist that contained a significantly reduced number of candidate genes from the critical region, yet still contained the causative gene. On average, a list of 163 genes based on position alone was reduced to a more manageable list of 22 genes based on position and expression or phenotype information. We are currently expanding the tool by adding other databases. The GeneSeeker is available via the web-interface (http://www.cmbi.kun.nl/GeneSeeker/).
    Nutrigenomics: goals and strategies
    Müller, M.R. ; Kersten, A.H. - \ 2003
    Nature Reviews Genetics 4 (2003). - ISSN 1471-0056 - p. 315 - 322.
    activated receptor-alpha - farnesoid-x-receptor - polyunsaturated fatty-acids - hepatic gene-expression - salt export pump - nuclear receptors - bile-acid - systems biology - human genome - oligonucleotide microarray
    Nutrigenomics is the application of high-throughput genomics tools in nutrition research. Applied wisely, it will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phase of a diet-related disease and to what extent individual sensitizing genotypes contribute to such diseases. Ultimately, nutrigenomics will allow effective dietary-Intervention strategies to recover normal homeostasis and to prevent diet-related diseases.
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