Enhancer chip: detecting human copy number variations in regulatory elements.
Critical functional properties are embedded in the non-coding portion of the human genome. Recent successful studies have shown that variations in distant-acting gene enhancer sequences can contribute to disease. In fact, various disorders, such as thalassaemias, preaxial polydactyly or susceptibili...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052264&type=printable |
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| author | Marco Savarese Giulio Piluso Daniela Orteschi Giuseppina Di Fruscio Manuela Dionisi Francesca del Vecchio Blanco Annalaura Torella Teresa Giugliano Michele Iacomino Marcella Zollino Giovanni Neri Vincenzo Nigro |
| author_facet | Marco Savarese Giulio Piluso Daniela Orteschi Giuseppina Di Fruscio Manuela Dionisi Francesca del Vecchio Blanco Annalaura Torella Teresa Giugliano Michele Iacomino Marcella Zollino Giovanni Neri Vincenzo Nigro |
| author_sort | Marco Savarese |
| collection | DOAJ |
| description | Critical functional properties are embedded in the non-coding portion of the human genome. Recent successful studies have shown that variations in distant-acting gene enhancer sequences can contribute to disease. In fact, various disorders, such as thalassaemias, preaxial polydactyly or susceptibility to Hirschsprung's disease, may be the result of rearrangements of enhancer elements. We have analyzed the distribution of enhancer loci in the genome and compared their localization to that of previously described copy-number variations (CNVs). These data suggest a negative selection of copy number variable enhancers. To identify CNVs covering enhancer elements, we have developed a simple and cost-effective test. Here we describe the gene selection, design strategy and experimental validation of a customized oligonucleotide Array-Based Comparative Genomic Hybridization (aCGH), designated Enhancer Chip. It has been designed to investigate CNVs, allowing the analysis of all the genome with a 300 Kb resolution and specific disease regions (telomeres, centromeres and selected disease loci) at a tenfold higher resolution. Moreover, this is the first aCGH able to test over 1,250 enhancers, in order to investigate their potential pathogenic role. Validation experiments have demonstrated that Enhancer Chip efficiently detects duplications and deletions covering enhancer loci, demonstrating that it is a powerful instrument to detect and characterize copy number variable enhancers. |
| format | Article |
| id | doaj-art-e27358dcfc8a4d88ae6fc455dca8ef90 |
| institution | DOAJ |
| issn | 1932-6203 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-e27358dcfc8a4d88ae6fc455dca8ef902025-08-20T03:09:48ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-01712e5226410.1371/journal.pone.0052264Enhancer chip: detecting human copy number variations in regulatory elements.Marco SavareseGiulio PilusoDaniela OrteschiGiuseppina Di FruscioManuela DionisiFrancesca del Vecchio BlancoAnnalaura TorellaTeresa GiuglianoMichele IacominoMarcella ZollinoGiovanni NeriVincenzo NigroCritical functional properties are embedded in the non-coding portion of the human genome. Recent successful studies have shown that variations in distant-acting gene enhancer sequences can contribute to disease. In fact, various disorders, such as thalassaemias, preaxial polydactyly or susceptibility to Hirschsprung's disease, may be the result of rearrangements of enhancer elements. We have analyzed the distribution of enhancer loci in the genome and compared their localization to that of previously described copy-number variations (CNVs). These data suggest a negative selection of copy number variable enhancers. To identify CNVs covering enhancer elements, we have developed a simple and cost-effective test. Here we describe the gene selection, design strategy and experimental validation of a customized oligonucleotide Array-Based Comparative Genomic Hybridization (aCGH), designated Enhancer Chip. It has been designed to investigate CNVs, allowing the analysis of all the genome with a 300 Kb resolution and specific disease regions (telomeres, centromeres and selected disease loci) at a tenfold higher resolution. Moreover, this is the first aCGH able to test over 1,250 enhancers, in order to investigate their potential pathogenic role. Validation experiments have demonstrated that Enhancer Chip efficiently detects duplications and deletions covering enhancer loci, demonstrating that it is a powerful instrument to detect and characterize copy number variable enhancers.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052264&type=printable |
| spellingShingle | Marco Savarese Giulio Piluso Daniela Orteschi Giuseppina Di Fruscio Manuela Dionisi Francesca del Vecchio Blanco Annalaura Torella Teresa Giugliano Michele Iacomino Marcella Zollino Giovanni Neri Vincenzo Nigro Enhancer chip: detecting human copy number variations in regulatory elements. PLoS ONE |
| title | Enhancer chip: detecting human copy number variations in regulatory elements. |
| title_full | Enhancer chip: detecting human copy number variations in regulatory elements. |
| title_fullStr | Enhancer chip: detecting human copy number variations in regulatory elements. |
| title_full_unstemmed | Enhancer chip: detecting human copy number variations in regulatory elements. |
| title_short | Enhancer chip: detecting human copy number variations in regulatory elements. |
| title_sort | enhancer chip detecting human copy number variations in regulatory elements |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0052264&type=printable |
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