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The KCNQ1OT1 imprin...
The KCNQ1OT1 imprinting control region and non-coding RNA : new properties derived from the study of Beckwith-Wiedemann syndrome and Silver-Russell syndrome cases
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Chiesa, Nicoletta (author)
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De Crescenzo, Agostina (author)
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- Mishra, Kankadeb (author)
- Uppsala universitet,Genomik
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Perone, Lucia (author)
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Carella, Massimo (author)
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Palumbo, Orazio (author)
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Mussa, Alessandro (author)
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Sparago, Angela (author)
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Cerrato, Flavia (author)
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Russo, Silvia (author)
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Lapi, Elisabetta (author)
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Cubellis, Maria Vittoria (author)
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- Kanduri, Chandrasekhar (author)
- Gothenburg University,Göteborgs universitet,Uppsala universitet,Genomik,Institutionen för biomedicin,Institute of Biomedicine
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Silengo, Margherita Cirillo (author)
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Riccio, Andrea (author)
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Ferrero, Giovanni Battista (author)
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(creator_code:org_t)
- 2011-09-14
- 2012
- English.
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 21:1, s. 10-25
- Related links:
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https://academic.oup...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
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- A cluster of imprinted genes at chromosome 11p15.5 is associated with the growth disorders, Silver-Russell syndrome (SRS) and Beckwith-Wiedemann syndrome (BWS). The cluster is divided into two domains with independent imprinting control regions (ICRs). We describe two maternal 11p15.5 microduplications with contrasting phenotypes. The first is an inverted and in cis duplication of the entire 11p15.5 cluster associated with the maintenance of genomic imprinting and with the SRS phenotype. The second is a 160 kb duplication also inverted and in cis, but resulting in the imprinting alteration of the centromeric domain. It includes the centromeric ICR (ICR2) and the most 5' 20 kb of the non-coding KCNQ1OT1 gene. Its maternal transmission is associated with ICR2 hypomethylation and the BWS phenotype. By excluding epigenetic mosaicism, cell clones analysis indicated that the two closely located ICR2 sequences resulting from the 160 kb duplication carried discordant DNA methylation on the maternal chromosome and supported the hypothesis that the ICR2 sequence is not sufficient for establishing imprinted methylation and some other property, possibly orientation-dependent, is needed. Furthermore, the 1.2 Mb duplication demonstrated that all features are present for correct imprinting at ICR2 when this is duplicated and inverted within the entire cluster. In the individuals maternally inheriting the 160 kb duplication, ICR2 hypomethylation led to the expression of a truncated KCNQ1OT1 transcript and to down-regulation of CDKN1C. We demonstrated by chromatin RNA immunopurification that the KCNQ1OT1 RNA interacts with chromatin through its most 5' 20 kb sequence, providing a mechanism likely mediating the silencing activity of this long non-coding RNA.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Chiesa, Nicolett ...
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De Crescenzo, Ag ...
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Mishra, Kankadeb
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Perone, Lucia
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Carella, Massimo
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Palumbo, Orazio
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Mussa, Alessandr ...
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Sparago, Angela
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Cerrato, Flavia
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Russo, Silvia
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Lapi, Elisabetta
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Cubellis, Maria ...
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Kanduri, Chandra ...
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Silengo, Margher ...
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Riccio, Andrea
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Ferrero, Giovann ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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Human Molecular ...
- By the university
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Uppsala University
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University of Gothenburg