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A quantitative transcriptome reference map of the normal human brain

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Abstract

We performed an innovative systematic meta-analysis of 60 gene expression profiles of whole normal human brain, to provide a quantitative transcriptome reference map of it, i.e. a reference typical value of expression for each of the 39,250 known, mapped and 26,026 uncharacterized (unmapped) transcripts. To this aim, we used the software named Transcriptome Mapper (TRAM), which is able to generate transcriptome maps based on gene expression data from multiple sources. We also analyzed differential expression by comparing the brain transcriptome with those derived from human foetal brain gene expression, from a pool of human tissues (except the brain) and from the two normal human brain regions cerebellum and cerebral cortex, which are two of the main regions severely affected when cognitive impairment occurs, as happens in the case of trisomy 21. Data were downloaded from microarray databases, processed and analyzed using TRAM software and validated in vitro by assaying gene expression through several magnitude orders by ‘real-time’ reverse transcription polymerase chain reaction (RT-PCR). The excellent agreement between in silico and experimental data suggested that our transcriptome maps may be a useful quantitative reference benchmark for gene expression studies related to the human brain. Furthermore, our analysis yielded biological insights about those genes which have an intrinsic over-/under-expression in the brain, in addition offering a basis for the regional analysis of gene expression. This could be useful for the study of chromosomal alterations associated to cognitive impairment, such as trisomy 21, the most common genetic cause of intellectual disability.

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Acknowledgments

We would like to give special thanks to the Fondazione Umano Progresso, Milano, Italy, for supporting the research on trisomy 21 conducted at the DIMES Dept. MC fellowship is funded by a donation from the company Illumia, Bologna, Italy, that we greatly thank for their interest in our research. We are grateful to Rotary Club, Cesena, Italy (President: Ing. Giuliano Arbizzani) for the generous donation of the thermal cycler ‘GenePro’ (Bioer). We thank all the other people that very kindly contributed by individual donations to support part of the work that we are conducting on the subject. In particular, we are profoundly grateful to Matteo and Elisa Mele, to the Costa, Dal Monte, Ghignone and Morini families as well as to the architects of the Jérôme Lejeune exhibition at the Rimini Meeting in 2012, to Rina Bini, to the ‘Gruppo Arzdore’ and the ‘Associazione Turistica Pro Loco di Dozza’ (Dozza, Bologna, Italy) for their generous support to our trisomy 21 research. We are grateful to Danielle Mitzman for her expert revision of the manuscript.

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Correspondence to Pierluigi Strippoli.

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Maria Chiara Pelleri and Allison Piovesan contributed equally to the work.

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Caracausi, M., Vitale, L., Pelleri, M.C. et al. A quantitative transcriptome reference map of the normal human brain. Neurogenetics 15, 267–287 (2014). https://doi.org/10.1007/s10048-014-0419-8

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