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      Inter-species differences of co-expression of neighboring genes in eukaryotic genomes

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          Abstract

          Background

          There is increasing evidence that gene order within the eukaryotic genome is not random. In yeast and worm, adjacent or neighboring genes tend to be co-expressed. Clustering of co-expressed genes has been found in humans, worm and fruit flies. However, in mice and rats, an effect of chromosomal distance (CD) on co-expression has not been investigated yet. Also, no cross-species comparison has been made so far. We analyzed the effect of CD as well as normalized distance (ND) using expression data in six eukaryotic species: yeast, fruit fly, worm, rat, mouse and human.

          Results

          We analyzed 24 sets of expression data from the six species. Highly co-expressed pairs were sorted into bins of equal sized intervals of CD, and a co-expression rate (CoER) in each bin was calculated. In all datasets, a higher CoER was obtained in a short CD range than a long distance range. These results show that across all studied species, there was a consistent effect of CD on co-expression. However, the results using the ND show more diversity. Intra- and inter-species comparisons of CoER reveal that there are significant differences in the co-expression rates of neighboring genes among the species. A pair-wise BLAST analysis finds 8 – 30 % of the highly co-expressed pairs are duplic ated genes.

          Conclusion

          We confirmed that in the six eukaryotic species, there was a consistent tendency that neighboring genes are likely to be co-expressed. Results of pair-wised BLAST indicate a significant effect of non-duplicated pairs on co-expression. A comparison of CD and ND suggests the dominant effect of CD.

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          Most cited references19

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          Prediction of central nervous system embryonal tumour outcome based on gene expression.

          Embryonal tumours of the central nervous system (CNS) represent a heterogeneous group of tumours about which little is known biologically, and whose diagnosis, on the basis of morphologic appearance alone, is controversial. Medulloblastomas, for example, are the most common malignant brain tumour of childhood, but their pathogenesis is unknown, their relationship to other embryonal CNS tumours is debated, and patients' response to therapy is difficult to predict. We approached these problems by developing a classification system based on DNA microarray gene expression data derived from 99 patient samples. Here we demonstrate that medulloblastomas are molecularly distinct from other brain tumours including primitive neuroectodermal tumours (PNETs), atypical teratoid/rhabdoid tumours (AT/RTs) and malignant gliomas. Previously unrecognized evidence supporting the derivation of medulloblastomas from cerebellar granule cells through activation of the Sonic Hedgehog (SHH) pathway was also revealed. We show further that the clinical outcome of children with medulloblastomas is highly predictable on the basis of the gene expression profiles of their tumours at diagnosis.
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            MLL translocations specify a distinct gene expression profile that distinguishes a unique leukemia.

            Acute lymphoblastic leukemias carrying a chromosomal translocation involving the mixed-lineage leukemia gene (MLL, ALL1, HRX) have a particularly poor prognosis. Here we show that they have a characteristic, highly distinct gene expression profile that is consistent with an early hematopoietic progenitor expressing select multilineage markers and individual HOX genes. Clustering algorithms reveal that lymphoblastic leukemias with MLL translocations can clearly be separated from conventional acute lymphoblastic and acute myelogenous leukemias. We propose that they constitute a distinct disease, denoted here as MLL, and show that the differences in gene expression are robust enough to classify leukemias correctly as MLL, acute lymphoblastic leukemia or acute myelogenous leukemia. Establishing that MLL is a unique entity is critical, as it mandates the examination of selectively expressed genes for urgently needed molecular targets.
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              Gene expression during the life cycle of Drosophila melanogaster.

              Molecular genetic studies of Drosophila melanogaster have led to profound advances in understanding the regulation of development. Here we report gene expression patterns for nearly one-third of all Drosophila genes during a complete time course of development. Mutations that eliminate eye or germline tissue were used to further analyze tissue-specific gene expression programs. These studies define major characteristics of the transcriptional programs that underlie the life cycle, compare development in males and females, and show that large-scale gene expression data collected from whole animals can be used to identify genes expressed in particular tissues and organs or genes involved in specific biological and biochemical processes.
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                Author and article information

                Journal
                BMC Genomics
                BMC Genomics
                BioMed Central (London )
                1471-2164
                2004
                13 January 2004
                : 5
                : 4
                Affiliations
                [1 ]Department of Biosystem Modeling, School of Biomedical Science, Tokyo Medical and Dental University, Tokyo, Japan
                [2 ]Department of Biomedical Information, Institute of Biomaterials and Biomedical Engineering, Tokyo Medical and Dental University, Tokyo, Japan
                [3 ]Informatics Program, Children's Hospital, Harvard Medical School, Boston, MA, USA
                [4 ]Division of Health Sciences and Technology, Harvard University and MIT, Cambridge, MA, USA
                [5 ]Harvard Partners Center for Genetics and Genomics, Boston, MA, USA
                Article
                1471-2164-5-4
                10.1186/1471-2164-5-4
                331401
                14718066
                e466af4b-e804-4a24-9ac4-efb77de571f2
                Copyright © 2004 Fukuoka et al; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.
                History
                : 7 August 2003
                : 13 January 2004
                Categories
                Research Article

                Genetics
                inter-species comparison,eukaryotic genome,chromosomal distance,co-expression
                Genetics
                inter-species comparison, eukaryotic genome, chromosomal distance, co-expression

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