Fred van Ruissen

Publications (25)111.18 Total impact

• Article: The phenotype of the Gly94fsX222 PMP22 insertion.

  Sara D J de Vries, Camiel Verhamme, Fred van Ruissen, Barbara W van Paassen, Willem F Arts, Henk Kerkhoff, Baziel G M van Engelen, Martin Lammens, Marianne de Visser, Frank Baas, Anneke J van der Kooi
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  ABSTRACT: Point mutations in PMP22 are relatively rare and the phenotype may vary from mild hereditary neuropathy with liability to pressure palsies (HNPP) to severe Charcot-Marie-Tooth type 1 (CMT1). We describe the phenotype of the Gly94fsX222 mutation in the PMP22 gene. Medical records of all patients were reviewed and 11 patients were re-examined. EMG was carried out in nine patients and nerve biopsy in one. Thirteen patients originating from seven families with a Gly94fsX222 mutation were included and consisted of 10 women and 3 men with a median age of 41 years (range 7-67). Five index patients were originally suspected of CMT1. Ten patients had abnormal motor skills during childhood. Nine patients had a history of pressure palsies. Involvement of the olfactory, trigeminal, facial, and pudendal nerves occurred in three patients. Twelve patients had pes cavus and one scoliosis. Distal anterior leg and distal arm weakness were found in 12 and 4 patients, respectively. Twelve patients had distal leg sensory abnormalities. Electrophysiological examination revealed a demyelinating sensorimotor neuropathy, both resembling CMT1 and HNPP. Sural nerve biopsy showed demyelinating neuropathy with presence of tomacula. More than three-fourths of the patients with Gly94fsX222 mutation demonstrated a CMT1 phenotype combined with transient deficits. Clinicians should test for this mutation in those patients exhibiting a generalised neuropathy combined with compressive like episodes.
  Journal of the Peripheral Nervous System 06/2011; 16(2):113-8. · 2.80 Impact Factor
• Article: TSEN54 mutations cause pontocerebellar hypoplasia type 5.

  Yasmin Namavar, David Chitayat, Peter G Barth, Fred van Ruissen, Marit B de Wissel, Bwee Tien Poll-The, Rachel Silver, Frank Baas
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  ABSTRACT: Pontocerebellar hypoplasia (PCH) is a group of autosomal recessive neurodegenerative disorders characterized by prenatal onset of stunted brain growth and progressive atrophy predominantly affecting cerebellum, pons and olivary nuclei, and to a lesser extent also the cerebral cortex. Six subtypes (PCH1-6) were described and genes for four types (PCH1, 2, 4 and 6) were identified. Mutations in the tRNA splicing endonuclease subunit (TSEN) genes 54, 2 and 34 are found in PCH2 and PCH4. One family with severe prenatal onset of PCH has been the only representative of PCH5 published so far, and the molecular genetic status of PCH5 has not been ascertained until now. We screened the previously reported PCH5 family for mutations in the TSEN54 gene. The PCH5 patient was found to be the result of compound heterozygosity for the common TSEN54 mutation (p.A307S) plus a novel splice site mutation. The mutations associated with PCH5 are similar to what has been reported in PCH4. Thus, PCH5, PCH4 and PCH2 represent a spectrum of clinical manifestations caused by different mutations in the TSEN genes. We, therefore, propose to classify PCH2, PCH4 and PCH5 as TSEN mutation spectrum disorders.
  European journal of human genetics: EJHG 02/2011; 19(6):724-6. · 3.56 Impact Factor
• Source

  Available from: John M Graham

  Article: Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia.

  Yasmin Namavar, Peter G Barth, Paul R Kasher, Fred van Ruissen, Knut Brockmann, Günther Bernert, Karin Writzl, Karen Ventura, Edith Y Cheng, Donna M Ferriero, [......], Linda De Meirleir, Mary King, John M Graham, Arpad von Moers, Nine Knoers, Laszlo Sztriha, Rudolf Korinthenberg, William B Dobyns, Frank Baas, Bwee Tien Poll-The
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  ABSTRACT: Pontocerebellar hypoplasia is a group of autosomal recessive neurodegenerative disorders with prenatal onset. The common characteristics are cerebellar hypoplasia with variable atrophy of the cerebellum and the ventral pons. Supratentorial involvement is reflected by variable neocortical atrophy, ventriculomegaly and microcephaly. Mutations in the transfer RNA splicing endonuclease subunit genes (TSEN54, TSEN2, TSEN34) were found to be associated with pontocerebellar hypoplasia types 2 and 4. Mutations in the mitochondrial transfer RNA arginyl synthetase gene (RARS2) were associated with pontocerebellar hypoplasia type 6. We studied a cohort of 169 patients from 141 families for mutations in these genes, of whom 106 patients tested positive for mutations in one of the TSEN genes or the RARS2 gene. In order to delineate the neuroradiological and clinical phenotype of patients with mutations in these genes, we compared this group with 63 patients suspected of pontocerebellar hypoplasia who were negative on mutation analysis. We found a strong correlation (P < 0.0005) between TSEN54 mutations and a dragonfly-like cerebellar pattern on magnetic resonance imaging, in which the cerebellar hemispheres are flat and severely reduced in size and the vermis is relatively spared. Mutations in TSEN54 are clinically associated with dyskinesia and/or dystonia and variable degrees of spasticity, in some cases with pure generalized spasticity. Nonsense or splice site mutations in TSEN54 are associated with a more severe phenotype of more perinatal symptoms, ventilator dependency and early death. In addition, we present ten new mutations in TSEN54, TSEN2 and RARS2. Furthermore, we show that pontocerebellar hypoplasia type 1 together with elevated cerebrospinal fluid lactate may be caused by RARS2 mutations.
  Brain 10/2010; 134(Pt 1):143-56. · 9.46 Impact Factor
• Article: X-linked Charcot-Marie-Tooth disease with novel c.47A>T GJB1 gene mutation.

  Alexander F J E Vrancken, Wim G M Spliet, Fred van Ruissen
  Journal of the Peripheral Nervous System 06/2010; 15(2):156-7. · 2.80 Impact Factor
• Article: Copy number variation upstream of PMP22 in Charcot-Marie-Tooth disease.

  Marian A J Weterman, Fred van Ruissen, Marit de Wissel, Lou Bordewijk, Johnny P A Samijn, W Ludo van der Pol, Farid Meggouh, Frank Baas
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  ABSTRACT: In several individuals with a Charcot-Marie-Tooth (CMT) phenotype, we found a copy number variation (CNV) on chromosome 17p12 in the direct vicinity of the peripheral myelin protein 22 (PMP22) gene. The exact borders and size of this CNV were determined by Southern blot analysis, MLPA, vectorette PCR, and microarray hybridization analyses. All patients from six apparently unrelated families carried an identical 186-kb duplication different from the commonly reported 1.5-Mb duplication associated with CMT1A. This ancestral mutation that was not reported in the human structural variation database was only detected in affected individuals and family members. It was absent in 2124 control chromosomes and 40 patients with a chronic inflammatory demyelinating polyneuropathy (CIDP) and therefore should be regarded as causative for the disease. This variant escapes most routine diagnostic screens for CMT1A, because copy numbers of PMP22 probes were all normal. No indications were found for the involvement of the genes that are located within this duplication. A possible association of this duplication with a mutation in the PMP22 coding regions was also excluded. We suggest that this CNV proximal of the PMP22 gene leads to CMT through an unknown mechanism affecting PMP22 expression.
  European journal of human genetics: EJHG 11/2009; 18(4):421-8. · 3.56 Impact Factor
• Article: Myoclonus-dystonia: clinical and genetic evaluation of a large cohort.

  K Ritz, M C F Gerrits, E M J Foncke, F van Ruissen, C van der Linden, M D I Vergouwen, B R Bloem, W Vandenberghe, R Crols, J D Speelman, F Baas, M A J Tijssen
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  ABSTRACT: Myoclonus-dystonia (M-D) is an autosomal dominant inherited movement disorder. Various mutations within the epsilon-sarcoglycan (SGCE) gene have been associated with M-D, but mutations are detected in only about 30% of patients. The lack of stringent clinical inclusion criteria and limitations of mutation screens by direct sequencing might explain this observation. Eighty-six M-D index patients from the Dutch national referral centre for M-D underwent neurological examination and were classified according to previously published criteria into definite, probable and possible M-D. Sequence analysis of the SGCE gene and screening for copy number variations were performed. In addition, screening was carried out for the 3 bp deletion in exon 5 of the DYT1 gene. Based on clinical examination, 24 definite, 23 probable and 39 possible M-D patients were detected. Thirteen of the 86 M-D index patients carried a SGCE mutation: seven nonsense mutations, two splice site mutations, three missense mutations (two within one patient) and one multiexonic deletion. In the definite M-D group, 50% carried an SGCE mutation and one single patient in the probable group (4%). One possible M-D patient showed a 4 bp deletion in the DYT1 gene (c.934_937delAGAG). Mutation carriers were mainly identified in the definite M-D group. However, in half of definite M-D cases, no mutation could be identified. Copy-number variations did not play a major role in the large cohort.
  Journal of neurology, neurosurgery, and psychiatry 01/2009; 80(6):653-8. · 4.87 Impact Factor
• Article: tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia.

  Birgit S Budde, Yasmin Namavar, Peter G Barth, Bwee Tien Poll-The, Gudrun Nürnberg, Christian Becker, Fred van Ruissen, Marian A J Weterman, Kees Fluiter, Erik T te Beek, [......], Francesco Muntoni, Colin D Ferrie, Roberta Battini, Raoul C M Hennekam, Eugenio Grillo, Frits A Beemer, Loes M E Stoets, Bernd Wollnik, Peter Nürnberg, Frank Baas
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  ABSTRACT: Pontocerebellar hypoplasias (PCH) represent a group of neurodegenerative autosomal recessive disorders with prenatal onset, atrophy or hypoplasia of the cerebellum, hypoplasia of the ventral pons, microcephaly, variable neocortical atrophy and severe mental and motor impairments. In two subtypes, PCH2 and PCH4, we identified mutations in three of the four different subunits of the tRNA-splicing endonuclease complex. Our findings point to RNA processing as a new basic cellular impairment in neurological disorders.
  Nature Genetics 09/2008; 40(9):1113-8. · 35.53 Impact Factor
• Article: Scaling of gene expression data allowing the comparison of different gene expression platforms.

  Fred van Ruissen, Gerben J Schaaf, Marcel Kool, Frank Baas, Jan M Ruijter
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  ABSTRACT: Serial analysis of gene expression (SAGE) and microarrays have found a widespread application, but much ambiguity exists regarding the amalgamation of the data resulting from these technologies. Cross-platform utilization of gene expression data from the SAGE and microarray technology could reduce the need for duplicate experiments and facilitate a more extensive exchange of data within the research community. This requires a measure for the correspondence of the results from different gene expression platforms. To date, a number of cross-platform evaluations (including a few studies using SAGE and Affymetrix GeneChips) have been conducted showing a variable, but overall low, concordance using different overall correlation approaches, such as Up/Down classification, contingency tables, and correlation coefficients. Here, we demonstrate an approach to compare two platforms based on the calculation of the difference between expression ratios observed in each platform for each individual transcript. This approach results in a concordance measure per gene, as opposed to the commonly used overall concordance measures between platforms. This between-ratio difference is a filtering-independent measure for between-platform concordance. Moreover, the between-ratio difference per gene can be used to identify transcripts with similar regulation on both platforms.
  Methods in molecular biology (Clifton, N.J.) 02/2008; 387:169-83.
• Article: Congenital hypomyelinating neuropathy, a long term follow-up study in an affected family.

  Liesbeth S Smit, Daniella Roofthooft, Fred van Ruissen, Frank Baas, Pieter A van Doorn
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  ABSTRACT: Congenital hypomyelinating neuropathy is a rare condition characterized by prenatal, neonatal or early infantile onset of hypotonia, paresis and areflexia. Most of the few patients described in literature die within the first years of life. Histopathologically there are no or thin myelin sheaths. Mutations have been described in the following genes, MPZ, EGR2, PMP22, and MTMR2. Here we describe a family with a heterozygous mutation in MPZ, confirmed in two generations.
  Neuromuscular Disorders 02/2008; 18(1):59-62. · 2.80 Impact Factor
• Article: Statistical comparison of two or more SAGE libraries: one tag at a time.

  Gerben J Schaaf, Fred van Ruissen, Antoine van Kampen, Marcel Kool, Jan M Ruijter
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  ABSTRACT: Several statistical tests have been introduced for the comparison of serial analysis of gene expression (SAGE) libraries to quantitatively analyze the differential expression of genes. As each SAGE library is only one measurement, the necessary information on biological variation or experimental precision is lacking. Therefore, each test includes its own approach to derive such a variance measure from the data set or a theoretical distribution. Because the confidence in tag counts depends on the library size, a test between two or more libraries should be based on original tag counts. When groups of libraries are compared, the test should determine that the proportion of a specific tag in all libraries is the same (null hypothesis), but also offer the possibility to detect specific differences between individual libraries and groups of libraries. The Z-test and the G-test encompass these characteristics and are described for the comparison of two libraries and (two or more) groups of libraries, respectively.
  Methods in molecular biology (Clifton, N.J.) 02/2008; 387:151-68.
• Chapter: Statistical Comparison of Two or More SAGE Libraries

  Gerben J. Schaaf, Fred van Ruissen, Antoine van Kampen, Marcel Kool, Jan M. Ruijter
  [show abstract] [hide abstract]
  ABSTRACT: Several statistical tests have been introduced for the comparison of serial analysis of gene expression (SAGE) libraries to quantitatively analyze the differential expression of genes. As each SAGE library is only one measurement, the necessary information on biological variation or experimental precision is lacking. Therefore, each test includes its own approach to derive such a variance measure from the data set or a theoretical distribution. Because the confidence in tag counts depends on the library size, a test between two or more libraries should be based on original tag counts. When groups of libraries are compared, the test should determine that the proportion of a specific tag in all libraries is the same (null hypothesis), but also offer the possibility to detect specific differences between individual libraries and groups of libraries. The Z-test and the G-test encompass these characteristics and are described for the comparison of two libraries and (two or more) groups of libraries, respectively. Key WordsSAGE-statistics–Z-test–binomial distribution–G-test–log–likelihood ratio–multinomial distribution–null hypothesis
  12/2007: pages 151-168;
• Article: Serial analysis of gene expression (SAGE).

  Fred van Ruissen, Frank Baas
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  ABSTRACT: In 1995, serial analysis of gene expression (SAGE) was developed as a versatile tool for gene expression studies. SAGE technology does not require pre-existing knowledge of the genome that is being examined and therefore SAGE can be applied to many different model systems. In this chapter, the SAGE procedure was described, which cannot only be used as a tool to generate gene expression profiles but also to identify new transcripts. SAGE data can easily be exchanged between laboratories and a large database with SAGE data is now available on the Internet.
  Methods in molecular biology (Clifton, N.J.) 02/2007; 383:41-66.
• Article: Comparison of Schwann cell and sciatic nerve transcriptomes indicates that mouse is a valid model for the human peripheral nervous system.

  Anneloor L M A Ten Asbroek, Fred Van Ruissen, Jan M Ruijter, Frank Baas
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  ABSTRACT: High-throughput gene expression analyses of murine models of the peripheral nervous system (PNS), and its cellular components, have yielded enormous amounts of expression data of the PNS in various conditions. These data provided clues for future research directions to further decipher this complex organ in relation to acquired and inherited PNS diseases. Various studies addressing the validity of mouse models for human conditions in other tissues and cell types have indicated that in many cases the mouse model only poorly represents the human situation. To determine how well the mouse can serve as model to study the biological processes occurring in the PNS, we compared the gene expression profiles that we generated for mouse and human sciatic nerve and cultured Schwann cells derived thereof. A two-way analysis based on the differentially expressed genes between the sciatic nerve and the cultured Schwann cell, and which takes into account the differential expression between mouse and man, indicates that the human PNS is well represented by that of the mouse in terms of the "biological processes" ontology.
  Journal of Neuroscience Research 09/2006; 84(3):542-52. · 2.74 Impact Factor
• Article: Full transcriptome analysis of rhabdomyosarcoma, normal, and fetal skeletal muscle: statistical comparison of multiple SAGE libraries.

  Gerben J Schaaf, Jan M Ruijter, Fred van Ruissen, Danny A Zwijnenburg, Raymond Waaijer, Linda J Valentijn, Jennifer Benit-Deekman, Antoine H C van Kampen, Frank Baas, Marcel Kool
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  ABSTRACT: Rhabdomyosarcoma (RMS) is the most frequent soft tissue sarcoma in children. Improved treatment strategies have increased overall survival, but the response of approximately one-third of the patients is still poor. To increase the knowledge of RMS pathogenesis, we performed the first full transcriptome analysis of RMS using serial analysis of gene expression (SAGE). With a G-test for the simultaneous comparison of subsets of SAGE libraries of normal skeletal muscle, embryonal (ERMS) and alveolar (ARMS) RMS, we identified 251 differentially expressed genes. A literature-mining procedure demonstrated that 158 of these genes have not previously been associated with RMS or normal muscle. Gene Ontology (GO) analysis assigned 198 of the 251 genes to muscle-specific classes, including those involved in normal myogenic development, as well as tumor-related classes. Prominent GO classes were those associated with proliferation and actin reorganization, which are processes that play roles during early muscle development, muscle function, and tumor progression. Using custom microarrays, we confirmed the (up- or down-) regulation of 80% of 98 differentially expressed genes. Another SAGE library of 19- to 22-week-old fetal skeletal muscle was compared with the RMS and normal muscle transcriptomes. Cluster analysis showed that the RMS and fetal muscle SAGE libraries formed one cluster distinct from normal muscle samples. Moreover, the expression profile of 86% of the differentially expressed genes between normal muscle and RMS was highly similar in fetal muscle and RMS. In conclusion, the G-test is a robust tool for analyzing groups of SAGE libraries and correctly identifies genes marking the difference between fully differentiated skeletal muscle and RMS. This study not only substantiates the close association between embryonic myogenesis and RMS development but also provides a rich source of candidate genes to further elucidate the etiology of RMS or to identify diagnostic and/or prognostic markers.
  The FASEB Journal 04/2005; 19(3):404-6. · 5.71 Impact Factor
• Article: Serial analysis of gene expression in human keratinocytes and epidermis.

  Bastiaan J H Jansen, Gys de Jongh, Joost Schalkwijk, Fred van Ruissen
  [show abstract] [hide abstract]
  ABSTRACT: The demand for large-scale gene expression analysis tools is on the rise now that several genomes have been sequenced. One of these tools, serial analysis of gene expression (SAGE), allows the qualitative as well as quantitative analysis of a large number of genes in a defined tissue or culture model. SAGE has already been successfully used to identify differentially expressed genes in normal physiological processes and pathological conditions. This chapter focuses on the SAGE protocol and its application to cultured human keratinocytes, and on MicroSAGE, an adapted protocol that allows the use of small amounts of mRNA from isolated epidermis or a skin biopsy.
  Methods in molecular biology (Clifton, N.J.) 02/2005; 289:383-98.
• Source

  Available from: Marcel Kool

  Article: Evaluation of the similarity of gene expression data estimated with SAGE and Affymetrix GeneChips.

  Fred van Ruissen, Jan M Ruijter, Gerben J Schaaf, Lida Asgharnegad, Danny A Zwijnenburg, Marcel Kool, Frank Baas
  [show abstract] [hide abstract]
  ABSTRACT: Serial Analysis of Gene Expression (SAGE) and microarrays have found a widespread application, but much ambiguity exists regarding the evaluation of these technologies. Cross-platform utilization of gene expression data from the SAGE and microarray technology could reduce the need for duplicate experiments and facilitate a more extensive exchange of data within the research community. This requires a measure for the correspondence of the different gene expression platforms. To date, a number of cross-platform evaluations (including a few studies using SAGE and Affymetrix GeneChips) have been conducted showing a variable, but overall low, concordance. This study evaluates these overall measures and introduces the between-ratio difference as a concordance measure pergene. In this study, gene expression measurements of Unigene clusters represented by both Affymetrix GeneChips HG-U133A and SAGE were compared using two independent RNA samples. After matching of the data sets the final comparison contains a small data set of 1094 unique Unigene clusters, which is unbiased with respect to expression level. Different overall correlation approaches, like Up/Down classification, contingency tables and correlation coefficients were used to compare both platforms. In addition, we introduce a novel approach to compare two platforms based on the calculation of differences between expression ratios observed in each platform for each individual transcript. This approach results in a concordance measure per gene (with statistical probability value), as opposed to the commonly used overall concordance measures between platforms. We can conclude that intra-platform correlations are generally good, but that overall agreement between the two platforms is modest. This might be due to the binomially distributed sampling variation in SAGE tag counts, SAGE annotation errors and the intensity variation between probe sets of a single gene in Affymetrix GeneChips. We cannot identify or advice which platform performs better since both have their (dis)-advantages. Therefore it is strongly recommended to perform follow-up studies of interesting genes using additional techniques. The newly introduced between-ratio difference is a filtering-independent measure for between-platform concordance. Moreover, the between-ratio difference per gene can be used to detect transcripts with similar regulation on both platforms.
  BMC Genomics 02/2005; 6:91. · 4.07 Impact Factor
• Article: Tumor necrosis factor related apoptosis inducing ligand triggers apoptosis in dividing but not in differentiating human epidermal keratinocytes.

  Bastiaan J H Jansen, Fred van Ruissen, Stefanie Cerneus, Wendy Cloin, Mieke Bergers, Piet E J van Erp, Joost Schalkwijk
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  ABSTRACT: Using serial analysis of gene expression we have previously identified the expression of several pro-apoptotic and anti-apoptotic genes in cultured human primary epidermal keratinocytes, including tumor necrosis factor related apoptosis inducing ligand (TRAIL). TRAIL is a potent inducer of apoptosis in transformed and tumor cell lines, but usually not in other cells. Here we present a study on the effect of TRAIL on cultured keratinocytes. It is shown that differentiated and undifferentiated keratinocytes undergo apoptosis after addition of TRAIL to the medium as determined by morphologic and biochemical criteria, such as cellular shrinkage and activation of caspases. The sensitivity for TRAIL differs greatly between undifferentiated and differentiating keratinocytes, however, with undifferentiated cells being much more susceptible to apoptosis. Commitment to terminal differentiation in the absence of TRAIL does not in itself induce apoptosis. In contrast to the promyelocytic cell line HL60, internucleosomal DNA fragmentation is not observed in keratinocytes, as assessed by flow cytometric analysis and agarose gel electrophoresis. Interestingly, the prime effector of DNA fragmentation, DNA fragmentation factor of 40 kDa (DFF40), is expressed in keratinocytes, yet internucleosomal cleavage fails to occur. Our data indicate that programmed cell death during keratinocyte differentiation is distinct from receptor-mediated apoptosis in response to a death ligand.
  Journal of Investigative Dermatology 01/2004; 121(6):1433-9. · 6.31 Impact Factor
• Article: Development of a keratinocyte-based screening model for antipsoriatic drugs using green fluorescent protein under the control of an endogenous promoter.

  Arno Pol, Fred van Ruissen, Joost Schalkwijk
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  ABSTRACT: Inflamed epidermis (psoriasis, wound healing, ultraviolet-irradiated skin) harbors keratinocytes that are hyperproliferative and display an abnormal differentiation program. A distinct feature of this so-called regenerative maturation pathway is the expression of proteins such as the cytokeratins CK6, CK16, and CK17 and the antiinflammatory protein SKALP/elafin. These proteins are absent in normal skin but highly induced in lesional psoriatic skin. Expression of these genes can be used as a surrogate marker for psoriasis in drug-screening procedures of large compound libraries. The aim of this study was to develop a keratinocyte cell line that contained a reporter gene under the control of a psoriasis-associated endogenous promoter and demonstrate its use in an assay suitable for screening. We generated a stably transfected keratinocyte cell line that expresses enhanced green fluorescent protein (EGFP), under the control of a 0.8-kb fragment derived from the promoter of the SKALP/elafin gene, which confers high levels of tissue-specific expression at the mRNA level. Induction of the SKALP promoter by tumor necrosis factor-alpha resulted in increased expression levels of the secreted SKALP-EGFP fusion protein as assessed by direct readout of fluorescence and fluorescence polarization in 96-well cell culture plates. The fold stimulation of the reporter gene was comparable to that of the endogenous SKALP gene as assessed by enzyme-linked immunosorbent assay. Although the dynamic range of the screening system is limited, the small standard deviation yields a Z factor of 0.49. This indicates that the assay is suitable as a high-throughput screen, and provides proof of the concept that a secreted EGFP fusion protein under the control of a physiologically relevant endogenous promoter can be used as a fluorescence-based high-throughput screen for differentiation-modifying or antiinflammatory compounds that act via the keratinocyte.
  Journal of Biomolecular Screening 09/2002; 7(4):325-32. · 2.05 Impact Factor
• Source

  Available from:

  Article: A partial transcriptome of human epidermis.

  Fred van Ruissen, Bastiaan J H Jansen, Gys J de Jongh, Patrick L J M Zeeuwen, Joost Schalkwijk
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  ABSTRACT: Serial analysis of gene expression (SAGE) is a powerful technique for global expression profiling without prior knowledge of the genes of interest. We carried out SAGE analysis of purified keratinocytes derived from human skin biopsy specimens, resulting in a partial transcriptome of human epidermis. We identified 7645 unique SAGE tags with quantitative information from 15,131 collected SAGE tags obtained from approximately 3 x 10(6) epidermal cells. This catalog contains a large number of genes that were not previously known to be expressed by human epidermis. Comparison with the databases of all known human SAGE tags allowed us to identify a number of keratinocyte-specific tags that putatively correspond to formerly unknown genes. Surprisingly, human epidermal keratinocytes in vivo show relatively low expression levels of genes typically associated with epidermal differentiation, whereas the expression levels of housekeeping genes are considerably higher than in cultured keratinocytes. This study provides a first step toward a transcriptome of human epidermis and, as such, harbors a wealth of information to identify genes involved in skin function, and candidate genes for genetic skin disorders.
  Genomics 06/2002; 79(5):671-8. · 3.02 Impact Factor
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  Available from:

  Article: Differential gene expression in premalignant human epidermis revealed by cluster analysis of serial analysis of gene expression (SAGE) libraries.

  Fred van Ruissen, Bastiaan J H Jansen, Gys J de Jongh, Ivonne M J J van Vlijmen-Willems, Joost Schalkwijk
  [show abstract] [hide abstract]
  ABSTRACT: Serial analysis of gene expression (SAGE) has been used for quantitative analysis of gene expression. We applied cluster analysis on multiple SAGE libraries derived from premalignant epidermal tissue (actinic keratosis), normal human epidermis, and cultured keratinocytes. The samples were obtained from skin biopsies without contamination by dermal tissue or blood. A total of 60,000 transcripts (tags) were analyzed. Two-way cluster analysis was applied to both the transcripts and the tissues, resulting in separation of the cultured cells from the epidermal samples, and clustering of many, presumably coregulated, genes. Two clusters of genes, strongly up-regulated in the tumor tissue compared with normal epidermis, were investigated in more detail. The differential expression of genes could be confirmed in actinic keratosis from four patients. Several of these genes have been previously associated with carcinogenesis or are likely to be important on the basis of their presumed function. Automated literature search tools show that a subgroup of these genes is coexpressed in other tissues and is part of an epidermal differentiation gene cluster on chromosome 1q21. We conclude that cluster analysis on large data sets uncovers clear partitions and correlations that could be confirmed by independent methods. We predict that these partitions will lead to biological interpretations that can be relevant for understanding the processes of carcinogenesis and tumor progression.
  The FASEB Journal 03/2002; 16(2):246-8. · 5.71 Impact Factor