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Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence

Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence
Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence
Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06–1.23 Mb upstream of SOX9, and microdeletions both approx1.5 Mb centromeric and approx1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements
1061-4036
359-364
Benko, Sabina
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Fantes, Judy A.
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Amiel, Judy A.
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Kleinjan, Dirk-Jan
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Thomas, Sophie
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Ramsay, Jacqueline
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Jamshidi, Negar
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Essafi, Abdelkader
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Heaney, Simon
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Gordon, Christopher T.
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McBride, David
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Golzio, Christelle
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Fisher, Malcolm
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Perry, Paul
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Abadie, Véronique
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Ayuso, Carmen
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Holder-Espinasse, Muriel
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Kilpatrick, Nicky
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Lees, Melissa M.
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Picard, Arnaud
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Temple, I. Karen
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Thomas, Paul
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Vazquez, Marie-Paule
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Vekemans, Michel
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Crollius, Hugues Roest
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Hastie, Nicholas D.
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Munnich, Arnold
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Etchevers, Heather C
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Pelet, Anna
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Farlie, Peter G.
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FitzPatrick, David R.
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Lyonnet, Stanislas
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Benko, Sabina
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Fantes, Judy A.
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Amiel, Judy A.
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Kleinjan, Dirk-Jan
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Thomas, Sophie
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Ramsay, Jacqueline
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Jamshidi, Negar
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Essafi, Abdelkader
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Heaney, Simon
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Gordon, Christopher T.
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McBride, David
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Golzio, Christelle
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Fisher, Malcolm
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Perry, Paul
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Abadie, Véronique
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Ayuso, Carmen
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Holder-Espinasse, Muriel
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Kilpatrick, Nicky
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Lees, Melissa M.
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Picard, Arnaud
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Temple, I. Karen
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Thomas, Paul
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Vazquez, Marie-Paule
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Vekemans, Michel
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Crollius, Hugues Roest
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Hastie, Nicholas D.
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Munnich, Arnold
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Etchevers, Heather C
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Pelet, Anna
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Farlie, Peter G.
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FitzPatrick, David R.
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Lyonnet, Stanislas
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Benko, Sabina, Fantes, Judy A., Amiel, Judy A., Kleinjan, Dirk-Jan, Thomas, Sophie, Ramsay, Jacqueline, Jamshidi, Negar, Essafi, Abdelkader, Heaney, Simon, Gordon, Christopher T., McBride, David, Golzio, Christelle, Fisher, Malcolm, Perry, Paul, Abadie, Véronique, Ayuso, Carmen, Holder-Espinasse, Muriel, Kilpatrick, Nicky, Lees, Melissa M., Picard, Arnaud, Temple, I. Karen, Thomas, Paul, Vazquez, Marie-Paule, Vekemans, Michel, Crollius, Hugues Roest, Hastie, Nicholas D., Munnich, Arnold, Etchevers, Heather C, Pelet, Anna, Farlie, Peter G., FitzPatrick, David R. and Lyonnet, Stanislas (2009) Highly conserved non-coding elements on either side of SOX9 associated with Pierre Robin sequence. Nature Genetics, 41 (3), 359-364. (doi:10.1038/ng.329).

Record type: Article

Abstract

Pierre Robin sequence (PRS) is an important subgroup of cleft palate. We report several lines of evidence for the existence of a 17q24 locus underlying PRS, including linkage analysis results, a clustering of translocation breakpoints 1.06–1.23 Mb upstream of SOX9, and microdeletions both approx1.5 Mb centromeric and approx1.5 Mb telomeric of SOX9. We have also identified a heterozygous point mutation in an evolutionarily conserved region of DNA with in vitro and in vivo features of a developmental enhancer. This enhancer is centromeric to the breakpoint cluster and maps within one of the microdeletion regions. The mutation abrogates the in vitro enhancer function and alters binding of the transcription factor MSX1 as compared to the wild-type sequence. In the developing mouse mandible, the 3-Mb region bounded by the microdeletions shows a regionally specific chromatin decompaction in cells expressing Sox9. Some cases of PRS may thus result from developmental misexpression of SOX9 due to disruption of very-long-range cis-regulatory elements

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Published date: February 2009

Identifiers

Local EPrints ID: 69515
URI: https://eprints.soton.ac.uk/id/eprint/69515
ISSN: 1061-4036
PURE UUID: c646543c-0282-4411-813e-bf6367935b03
ORCID for I. Karen Temple: ORCID iD orcid.org/0000-0002-6045-1781

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Date deposited: 18 Nov 2009
Last modified: 29 Oct 2019 01:59

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Contributors

Author: Sabina Benko
Author: Judy A. Fantes
Author: Judy A. Amiel
Author: Dirk-Jan Kleinjan
Author: Sophie Thomas
Author: Jacqueline Ramsay
Author: Negar Jamshidi
Author: Abdelkader Essafi
Author: Simon Heaney
Author: Christopher T. Gordon
Author: David McBride
Author: Christelle Golzio
Author: Malcolm Fisher
Author: Paul Perry
Author: Véronique Abadie
Author: Carmen Ayuso
Author: Muriel Holder-Espinasse
Author: Nicky Kilpatrick
Author: Melissa M. Lees
Author: Arnaud Picard
Author: I. Karen Temple ORCID iD
Author: Paul Thomas
Author: Marie-Paule Vazquez
Author: Michel Vekemans
Author: Hugues Roest Crollius
Author: Nicholas D. Hastie
Author: Arnold Munnich
Author: Heather C Etchevers
Author: Anna Pelet
Author: Peter G. Farlie
Author: David R. FitzPatrick
Author: Stanislas Lyonnet

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