Biomedical subjects

Antoine H C van Kampen

Publications and source records attributed to Antoine H C van Kampen.

5 recordsLinked to original sources

PubMed2006

Compositional discordance between prokaryotic plasmids and host chromosomes.

BACKGROUND: Most plasmids depend on the host replication machinery and possess partitioning genes. These properties confine plasmids to a limited range of hosts, yielding a close and presumably stable relationship between plasmid and host. Hence, it is anticipated that due to amelioration the dinucleotide composition of plasmids is similar to that of the genome of their hosts. However, plasmids are also thought to play a major role in horizontal gene transfer and thus are frequently exchanged between hosts, suggesting dinucleotide composition dissimilarity between plasmid and host genome. We compared the dinucleotide composition of a large collection of plasmids with that of their host genomes to shed more light on this enigma. RESULTS: The dinucleotide frequency, coined the genome signature, facilitates the identification of putative horizontally transferred DNA in complete genome sequences, since it was found to be typical for a certain genome, and similar between related species. By comparison of the genome signature of 230 plasmid sequences with that of the genome of each respective host, we found that in general the genome signature of plasmids is dissimilar from that of their host genome. CONCLUSION: Our results show that the genome signature of plasmids does not resemble that of their host genome. This indicates either absence of amelioration or a less stable relationship between plasmids and their host. We propose an indiscriminate lifestyle for plasmids preserving the genome signature discordance between these episomes and host chromosomes.

Base Composition↗

PubMed2006

Inosine triphosphate pyrophosphatase and thiopurine s-methyltransferase genotypes relationship to azathioprine-induced myelosuppression.

BACKGROUND & AIMS: The use of azathioprine (AZA) in inflammatory bowel disease (IBD) patients is limited by toxicity, which occurs in up to 20% of treated patients. Mutations in the thiopurine S-methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) genes have been associated with the occurrence of AZA-related toxicity. The aim of our study was to determine the relative contribution of ITPA and TPMT mutations to the development of toxicity induced by AZA treatment in IBD patients. METHODS: ITPA(94C>A, IVS2+21A>C) and TPMT (238G>C, 460G>A, and 719A>G) genotypes were assessed in 262 IBD patients (159 females, 103 males; 67 patients with ulcerative colitis, 195 patients with Crohn's disease) treated with AZA and were correlated with the development of leukopenia and hepatotoxicity. RESULTS: Leukopenia (leukocyte count, <3.0 x 10(9)/L) was observed in 4.6% of treated patients. The frequencies of mutant ITPA 94C>A and TPMT alleles were significantly higher in the leukopenic population compared with patients without leukopenia (16.7% and 5.4%, respectively, for ITPA 94C>A, and 20.8% and 4%, respectively, for TPMT). Moreover, the ITPA 94C>A and TPMT mutations predicted leukopenia: ITPA 94C>A odds ratio, 3.504; 95% confidence interval, 1.119-10.971 (P = .046); TPMT odds ratio, 6.316; 95% confidence interval, 2.141-18.634 (P = .004). Neither TPMT nor ITPA genotype predicted hepatotoxicity. CONCLUSIONS: ITPA 94C>A and TPMT polymorphisms are associated with AZA-related leukopenia in IBD patients.

Adolescent↗

PubMed2006

Identification of acquired DNA in Neisseria lactamica.

Anomalous DNA (aDNA) in prokaryotic genomes, identified by its aberrant nucleotide composition, generally represents horizontally acquired DNA. Previous studies showed that frequent DNA transfer occurs between commensal Neisseriae and Neisseria meningitidis. Currently, it is unknown whether aDNA regions are also transferred between these species. The genome of Neisseria lactamica strain 892586 was assessed by a strategy that enables the selective isolation of aDNA, using endonucleases with recognition sites that are overrepresented in aDNA. Of eight regions with aDNA, five displayed similarity to virulence-associated meningococcal sequences. Of three aDNA fragments with limited or no similarity to neisserial sequences, one encodes a novel putative autotransporter/adhesin. The remaining two fragments are adjacent in the N. lactamica genome, and encode a novel putative ATPase/subtilisin-like protease operon. A similar operon is present in the genomes of different respiratory tract pathogens. The identification of aDNA from N. lactamica with similarity to meningococcal aDNA shows that genetic exchange between the Neisseriae is not limited to the neisserial core genome. The discovery of aDNA in N. lactamica similar to a locus in other pathogens substantially expands the neisserial gene pool.

Adenosine Triphosphatases↗

PubMed2005

Full transcriptome analysis of rhabdomyosarcoma, normal, and fetal skeletal muscle: statistical comparison of multiple SAGE libraries.

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.

Cell Adhesion↗

PubMed2003

The human transcriptome map reveals extremes in gene density, intron length, GC content, and repeat pattern for domains of highly and weakly expressed genes.

The chromosomal gene expression profiles established by the Human Transcriptome Map (HTM) revealed a clustering of highly expressed genes in about 30 domains, called ridges. To physically characterize ridges, we constructed a new HTM based on the draft human genome sequence (HTMseq). Expression of 25,003 genes can be analyzed online in a multitude of tissues (http://bioinfo.amc.uva.nl/HTMseq). Ridges are found to be very gene-dense domains with a high GC content, a high SINE repeat density, and a low LINE repeat density. Genes in ridges have significantly shorter introns than genes outside of ridges. The HTMseq also identifies a significant clustering of weakly expressed genes in domains with fully opposite characteristics (antiridges). Both types of domains are open to tissue-specific expression regulation, but the maximal expression levels in ridges are considerably higher than in antiridges. Ridges are therefore an integral part of a higher order structure in the genome related to transcriptional regulation.

Base Composition↗