Integrated Quantitative Transcriptome Maps of Human Trisomy 21 Tissues and Cells
Open accessAbstract
Down syndrome (DS) is due to the presence of an extra full or partial chromosome 21 (Hsa21). The identification of genes contributing to DS pathogenesis could be the key to any rational therapy of the associated intellectual disability. We aim at generating quantitative transcriptome maps in DS integrating all gene expression profile datasets available for any cell type or tissue, to obtain a complete model of the transcriptome in terms of both expression values for each gene and segmental trend of gene expression along each chromosome. We used the TRAM (Transcriptome Mapper) software for this meta-analysis, comparing transcript expression levels and profiles between DS and normal brain, lymphoblastoid cell lines, blood cells, fibroblasts, thymus and induced pluripotent stem cells, respectively. TRAM combined, normalized and integrated datasets from different sources and across diverse experimental platforms. The main output was a linear expression value that may be used as a reference for each of up to 37,181 mapped transcripts analyzed, related to both known genes and expression sequence tag (EST) clusters. An independent example in vitro validation of fibroblast transcriptome map data was performed through “Real-Time” reverse transcription polymerase chain reaction showing an excellent correlation coefficient (r=0.93, p<0.0001) with data obtained in silico. The availability of linear expression values for each gene allowed the testing of the gene dosage hypothesis of the expected 3:2 DS/normal ratio for Hsa21 as well as other human genes in DS, in addition to listing genes differentially expressed with statistical significance. Although a fraction of Hsa21 genes escapes dosage effects, Hsa21 genes are selectively over-expressed in DS samples compared to genes from other chromosomes, reflecting a decisive role in the pathogenesis of the syndrome. Finally, the analysis of chromosomal segments reveals a high prevalence of Hsa21 over-expressed segments over the other genomic regions, suggesting, in particular, a specific region on Hsa21 that appears to be frequently over-expressed (21q22). Our complete datasets are released as a new framework to investigate transcription in DS for individual genes as well as chromosomal segments in different cell types and tissues.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2−ΔΔCT Method
Livak, K. J., & Schmittgen, T. D. (2001) · Methods · doi:10.1006/meth.2001.1262 · Cited by 180,860 · see citing works
Single-Step Method of RNA Isolation by Acid Guanidinium Thiocyanate–Phenol–Chloroform Extraction
Chomczynski, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1006/abio.1987.9999 · Cited by 65,240 · see citing works
Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction
Chomczyński, P., & Sacchi, N. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90021-2 · Cited by 47,092 · see citing works
Genome-wide atlas of gene expression in the adult mouse brain
Lein, E. S., Hawrylycz, M. J., Ao, N., Ayres, M., Bensinger, A., Bernard, A., Boe, A. F., Boguski, M. S., Brockway, K. S., Byrnes, E. J., et al. (2007) · Nature · doi:10.1038/nature05453 · Cited by 5,572 · see citing works
Mutation of the mouse klotho gene leads to a syndrome resembling ageing
Kuro-o, M., Matsumura, Y., Aizawa, H., Kawaguchi, H., Suga, T., Utsugi, T., Ohyama, Y., Kurabayashi, M., Kaname, T., Kume, E., et al. (1997) · Nature · doi:10.1038/36285 · Cited by 3,837 · see citing works
ToppGene Suite for gene list enrichment analysis and candidate gene prioritization
Chen, J., Bardes, E. E., Aronow, B. J., & Jegga, A. G. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp427 · Cited by 2,952 · see citing works
Microarray data normalization and transformation
Quackenbush, J. (2002) · Nature Genetics · doi:10.1038/ng1032 · Cited by 1,975 · see citing works
The DNA sequence of human chromosome 21
Hattori, M., Fujiyama, A., Taylor, T. D., Watanabe, H., Yada, T., Park, H.-S., Toyoda, A., Ishii, K., Totoki, Y., Choi, D., et al. (2000) · Nature · doi:10.1038/35012518 · Cited by 1,475 · see citing works
[19] Gene Expression Omnibus: Microarray Data Storage, Submission, Retrieval, and Analysis
Barrett, T., & Edgar, R. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(06)11019-8 · Cited by 511 · see citing works
Neuroanatomy of Down’s Syndrome: A High-Resolution MRI Study
Pinter, J. D., Eliez, S., Schmitt, J. E., Capone, G. T., & Reiss, A. L. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.10.1659 · Cited by 452 · see citing works
Trisomy 21 consistently activates the interferon response
Sullivan, K. D., Lewis, H. C., Hill, A. A., Pandey, A., Jackson, L. P., Cabral, J. M., Smith, K. P., Liggett, L. A., Gomez, E. B., Galbraith, M. D., et al. (2016) · eLife · doi:10.7554/elife.16220 · Cited by 362 · see citing works
Aït Yahya-Graison, E., Aubert, J., Dauphinot, L., Rivals, I., Prieur, M., Golfier, G., Rossier, J., Personnaz, L., Créau, N., Bléhaut, H., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/520000 · Cited by 338 · see citing works
AltAnalyze and DomainGraph: analyzing and visualizing exon expression data
Emig, D., Salomonis, N., Baumbach, J., Lengauer, T., Conklin, B. R., & Albrecht, M. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkq405 · Cited by 324 · see citing works
Domains of genome-wide gene expression dysregulation in Down’s syndrome
Letourneau, A., Santoni, F. A., Bonilla, X., Sailani, M. R., Gonzalez, D., Kind, J., Chevalier, C., Thurman, R., Sandstrom, R. S., Hibaoui, Y., et al. (2014) · Nature · doi:10.1038/nature13200 · Cited by 319 · see citing works
Dendritic atrophy in children with down’s syndrome.
Becker, L. E., Armstrong, D. L., & Chan, F. (1986) · Annals of Neurology · doi:10.1002/ana.410200413 · Cited by 279 · see citing works
Down syndrome and the complexity of genome dosage imbalance
Antonarakis, S. (2016) · Nature reviews genetics · doi:10.1038/nrg.2016.154 · Cited by 264 · see citing works
Gene expression profiling in the adult Down syndrome brain
Lockstone, H. E., Harris, L. W., Swatton, J. E., Wayland, M. T., Holland, A. J., & Bahn, S. (2007) · Genomics · doi:10.1016/j.ygeno.2007.08.005 · Cited by 240 · see citing works
Olmos-Serrano, J. L., Kang, H. J., Tyler, W. A., Silbereis, J. C., Cheng, F., Zhu, Y., Pletikos, M., Jankovic-Rapan, L., Cramer, N. P., Galdzicki, Z., et al. (2016) · Neuron · doi:10.1016/j.neuron.2016.01.042 · Cited by 239 · cited 3× · see citing works
“…terms of mean expression level derived from all the genes on that chromosome) showed that the most over-expressed chromosome, in proportion, is Hsa21 in all analyzed maps, in accordance with the most recently published results (Weick et al., 2013; Olmos-Serrano et al., 2016; Sullivan et al., 2016).”
BackgroundResultDo you know the sex of your cells?
Shah, K., McCormack, C. E., & Bradbury, N. A. (2014) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00281.2013 · Cited by 219 · see citing works
Deficits in human trisomy 21 iPSCs and neurons
Weick, J. P., Held, D. L., Bonadurer, G. F., Doers, M. E., Liu, Y., Maguire, C., Clark, A., Knackert, J. A., Molinarolo, K., Musser, M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1216575110 · Cited by 205 · see citing works
Natural Gene-Expression Variation in Down Syndrome Modulates the Outcome of Gene-Dosage Imbalance
Prandini, P., Deutsch, S., Lyle, R., Gagnebin, M., Delucinge-Vivier, C., Delorenzi, M., Gehrig, C., Descombes, P., Sherman, S. L., Bricarelli, F. D., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519248 · Cited by 196 · see citing works
Contributing software to the internet: the amplify program
Engels, W. R. (1993) · Trends in Biochemical Sciences · doi:10.1016/0968-0004(93)90148-g · Cited by 170 · see citing works
Guidi, S., Ciani, E., Bonasoni, P., Santini, D., & Bartesaghi, R. (2011) · Brain Pathology · doi:10.1111/j.1750-3639.2010.00459.x · Cited by 165 · see citing works
Generation of Genomic Deletions in Mammalian Cell Lines via CRISPR/Cas9
Bauer, D. E., Canver, M. C., & Orkin, S. H. (2014) · Journal of Visualized Experiments · doi:10.3791/52118 · Cited by 158 · see citing works
Briggs, J. A., Sun, J., Shepherd, J., Ovchinnikov, D. A., Chung, T.-L., Nayler, S. P., Kao, L.-P., Morrow, C. A., Thakar, N. Y., Soo, S.-Y., et al. (2013) · Stem Cells · doi:10.1002/stem.1297 · Cited by 151 · see citing works
Down Syndrome: From Understanding the Neurobiology to Therapy
Gardiner, K., Hérault, Y., Lott, I. T., Antonarakis, S. E., Reeves, R. H., & Dierssen, M. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.3728-10.2010 · Cited by 149 · see citing works
Global disruption of the cerebellar transcriptome in a Down syndrome mouse model
Saran, N. G. (2003) · Human Molecular Genetics · doi:10.1093/hmg/ddg217 · Cited by 143 · see citing works
Systematic proteome and proteostasis profiling in human trisomy 21 fibroblast cells
Liu, Y., Borel, C., Li, L., Müller, T., Williams, E. G., Germain, P.-L., Buljan, M., Sajic, T., Boersema, P. J., Shao, W., et al. (2017) · Nature Communications · doi:10.1038/s41467-017-01422-6 · Cited by 141 · see citing works
The European Bioinformatics Institute's data resources
Brooksbank, C., Cameron, G. N., & Thornton, J. M. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp986 · Cited by 138 · see citing works
Vilardell, M., Rasche, A., Thormann, A., Maschke-Dutz, E., Jurado, L. A. P., Lehrach, H. R., & Herwig, R. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-229 · Cited by 127 · see citing works
[Human chromosomes in tissue cultures].
LEJEUNE, J., GAUTHIER, M., & Turpin, R. (1959) · PubMed · Cited by 118 · see citing works
Piovesan, A., Caracausi, M., Antonaros, F., Pelleri, M. C., & Vitale, L. (2016) · Database · doi:10.1093/database/baw153 · Cited by 113 · see citing works
Self-citationCaracausi, M., Ghini, V., Locatelli, C., Mericio, M., Piovesan, A., Antonaros, F., Pelleri, M. C., Vitale, L., Vacca, R. A., Bedetti, F., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-20834-y · Cited by 84 · see citing works
Self-citationPelleri, M. C., Cicchini, E., Locatelli, C., Vitale, L., Caracausi, M., Piovesan, A., Rocca, A., Poletti, G., Seri, M., Strippoli, P., et al. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw116 · Cited by 83 · see citing works
Self-citationCharacterization of the Bex gene family in humans, mice, and rats
Álvarez, E., Zhou, W., Witta, S. E., et al. (2005) · Gene · doi:10.1016/j.gene.2005.05.012 · Cited by 81 · see citing works
Caracausi, M., Piovesan, A., Antonaros, F., Strippoli, P., Vitale, L., & Pelleri, M. C. (2017) · Molecular Medicine Reports · doi:10.3892/mmr.2017.6944 · Cited by 81 · see citing works
Self-citationLEJEUNE, J. (1981) · PubMed · Cited by 67 · see citing works
Mariani, E., Frabetti, F., Tarozzi, A., Pelleri, M. C., Pizzetti, F., & Casadei, R. (2016) · PLoS ONE · doi:10.1371/journal.pone.0161567 · Cited by 65 · see citing works
Self-citationThe European Bioinformatics Institute’s data resources 2014
Brooksbank, C., Bergman, M. T., Apweiler, R., Birney, E., & Thornton, J. M. (2013) · Nucleic Acids Research · doi:10.1093/nar/gkt1206 · Cited by 60 · see citing works
Guedj, F., Pennings, J. L. A., Massingham, L. J., Wick, H. C., Siegel, A. E., Tantravahi, U., & Bianchi, D. W. (2016) · Scientific Reports · doi:10.1038/srep32353 · Cited by 59 · see citing works
Piovesan, A., Caracausi, M., Ricci, M., Strippoli, P., Vitale, L., & Pelleri, M. C. (2015) · DNA Research · doi:10.1093/dnares/dsv028 · Cited by 56 · see citing works
Self-citationPathways to cognitive deficits in Down syndrome
Sturgeon, X., Le, T., Ahmed, M. M., & Gardiner, K. (2012) · Progress in brain research · doi:10.1016/b978-0-444-54299-1.00005-4 · Cited by 51 · see citing works
Rodia, M. T., Ugolini, G., Mattei, G., Montroni, I., Zattoni, D., Ghignone, F., Veronese, G., Marisi, G., Lauriola, M., Strippoli, P., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8108 · Cited by 43 · see citing works
Self-citationLenzi, L., Facchin, F., Piva, F., Giulietti, M., Pelleri, M. C., Frabetti, F., Vitale, L., Casadei, R., Canaider, S., Bortoluzzi, S., et al. (2011) · BMC Genomics · doi:10.1186/1471-2164-12-121 · Cited by 40 · see citing works
Self-citationBaldo, C., Casareto, L., Renieri, A., et al. (2016) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-016-0527-7 · Cited by 39 · see citing works
Chromosome 21: from sequence to applications
Antonarakis, S. E. (2001) · Current Opinion in Genetics & Development · doi:10.1016/s0959-437x(00)00185-4 · Cited by 32 · see citing works
UniGene Tabulator: a full parser for the UniGene format
Lenzi, L., Frabetti, F., Facchin, F., et al. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl425 · Cited by 32 · see citing works
Clinical Aspects of Down’s Syndrome from Infancy to Adult Life
Tolksdorf, M., & Wiedemann, H. ‐. (1981) · Human genetics. Supplement · doi:10.1007/978-3-642-68006-9_2 · Cited by 29 · see citing works
Bioinformatics analysis of biomarkers and transcriptional factor motifs in Down syndrome
Kong, X., Liu, N., & Xu, X. (2014) · Brazilian Journal of Medical and Biological Research · doi:10.1590/1414-431x20143792 · Cited by 28 · see citing works
A quantitative transcriptome reference map of the normal human brain
Caracausi, M., Vitale, L., Pelleri, M. C., Piovesan, A., Bruno, S., & Strippoli, P. (2014) · Neurogenetics · doi:10.1007/s10048-014-0419-8 · Cited by 27 · see citing works
Self-citationPelleri, M. C., Piovesan, A., Caracausi, M., Berardi, A. C., Vitale, L., & Strippoli, P. (2014) · BMC Medical Genomics · doi:10.1186/s12920-014-0063-z · Cited by 25 · see citing works
Self-citationIdentification and characterization of two novel (neuro)endocrine long coiled‐coil proteins
Cruz-García, D., Vázquez‐Martínez, R., Peinado, J. R., et al. (2007) · FEBS Letters · doi:10.1016/j.febslet.2007.06.002 · Cited by 23 · see citing works
Integrated Transcriptome Map Highlights Structural and Functional Aspects of the Normal Human Heart
Caracausi, M., Piovesan, A., Vitale, L., & Pelleri, M. C. (2016) · Journal of Cellular Physiology · doi:10.1002/jcp.25471 · Cited by 23 · see citing works
Self-citationA quantitative transcriptome reference map of the normal human hippocampus
Caracausi, M., Rigon, V., Piovesan, A., Strippoli, P., Vitale, L., & Pelleri, M. C. (2015) · Hippocampus · doi:10.1002/hipo.22483 · Cited by 22 · see citing works
Self-citationVitale, L., Piovesan, A., Antonaros, F., Strippoli, P., Pelleri, M. C., & Caracausi, M. (2017) · BMC Genomics · doi:10.1186/s12864-017-4049-z · Cited by 22 · see citing works
Self-citationPiovesan, A., Vitale, L., Pelleri, M. C., & Strippoli, P. (2013) · Genomics · doi:10.1016/j.ygeno.2013.02.009 · Cited by 21 · see citing works
Self-citationMoldrich, R. X., Lainé, J., Visel, A., Beart, P. M., Laffaire, J., Rossier, J., & Potier, M. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.01.089 · Cited by 20 · see citing works
Expression Signature as a Biomarker for Prenatal Diagnosis of Trisomy 21
Volk, M., Maver, A., Lovrečić, L., Juvan, P., & Peterlin, B. (2013) · PLoS ONE · doi:10.1371/journal.pone.0074184 · Cited by 19 · see citing works
Molecular mapping of the Down syndrome phenotype.
Korenberg, J. R. (1990) · PubMed · Cited by 18 · see citing works
Questioned validity of Gene Expression Dysregulated Domains in Down's Syndrome
Do, L. H., Mobley, W. C., & Singhal, N. (2015) · F1000Research · doi:10.12688/f1000research.6735.1 · Cited by 17 · see citing works
Co-expression network analysis of Down's syndrome based on microarray data
Zhao, J., Zhang, Z., Ren, S., Zong, Y., & Kong, X. (2016) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2016.3462 · Cited by 12 · see citing works
Díaz‐Ruiz, A., Rabanal‐Ruiz, Y., Trávez, A., Gracia‐Navarro, F., Cruz-García, D., Montero‐Hadjadje, M., Anouar, Y., Gasman, S., Vitale, N., Vázquez‐Martínez, R., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0073668 · Cited by 7 · see citing works
LEJEUNE, J. (1981) · Human genetics. Supplement · doi:10.1007/978-3-642-68006-9_8 · Cited by 4 · see citing works
Vitale, L., Caracausi, M., Casadei, R., Pelleri, M. C., & Piovesan, A. (2017) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2017.2942 · Cited by 4 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Sharrocks A. (1994). “The design of primer for PCR,” in PCR Technology—Current Innovations, eds Griffin H. G. Griffin A. M. (Boca Raton, FL: CRC Press), 5– 11.
Cited by
Sorted by citations
On the length, weight and GC content of the human genome
Piovesan, A., Pelleri, M. C., Antonaros, F., Strippoli, P., Caracausi, M., & Vitale, L. (2019) · BMC Research Notes · doi:10.1186/s13104-019-4137-z · Cited by 283 · see citing works
Self-citationAstrocytes in Down Syndrome Across the Lifespan
Ponroy Bally, B., & Murai, K. K. (2021) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2021.702685 · Cited by 35 · see citing works
- Authors
- Pelleri, M. C., Cattani, C., Vitale, L., Antonaros, F., Strippoli, P., Locatelli, C., Cocchi, G., Piovesan, A., & Caracausi, M.
- Affiliations
- University of Bologna (IT)
- IRCCS Azienda Ospedliero-Universitaria di Bologna Policlinico di Sant'Orsola (IT)
- Corresponding author
- Piovesan, Allison
- ORCID
- Venue
- Frontiers in Genetics
- Publisher
- Frontiers Media SA
- Published
- 2018-04-24
- Volume
- 9
- Pages
- 125-125
- ISSN
- 1664-8021 (ISSN-L)
- PMC
- PMC5928158
- OpenAlex
- W2802174253
- Cited by
- 61
- References
- 64
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 7 · 2023: 8 · 2022: 5 · 2021: 14 · 2020: 12 · 2019: 8
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Frontiers in Genetics (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Down syndrome and intellectual disability research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- Down syndrome, transcriptome mapping, gene expression, intellectual disability, fibroblasts, lymphoblastoid cell lines, induced pluripotent stem cells, thymus, brain, blood cells, expressed sequence tags
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
