Enhancer elements upstream of the SHOX gene are active in the developing limb

C Durand, Fiona Bangs, Jason Signolet, E Decker, Cheryll Tickle, G Rappold

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Leri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.
Original languageEnglish
Pages (from-to)527-532
Number of pages6
JournalEuropean Journal of Human Genetics
Volume18
Issue number5
DOIs
Publication statusPublished - May 2010

Fingerprint

Extremities
Cornea
Genes
Chickens
Limb Buds
Haploinsufficiency
Nucleic Acid Regulatory Sequences
Gene Deletion
Transcription Factors
Phenotype
Bone and Bones
Mutation
Leri-Weil syndrome

Keywords

  • enhancer
  • Leri-Weill dyschondrosteosis
  • homeobox gene
  • SHOX
  • short stature

Cite this

Enhancer elements upstream of the SHOX gene are active in the developing limb. / Durand, C; Bangs, Fiona; Signolet, Jason; Decker, E; Tickle, Cheryll; Rappold, G.

In: European Journal of Human Genetics, Vol. 18, No. 5, 05.2010, p. 527-532.

Research output: Contribution to journalArticle

Durand, C ; Bangs, Fiona ; Signolet, Jason ; Decker, E ; Tickle, Cheryll ; Rappold, G. / Enhancer elements upstream of the SHOX gene are active in the developing limb. In: European Journal of Human Genetics. 2010 ; Vol. 18, No. 5. pp. 527-532.
@article{a6284276ca3642e8824f12c271318e59,
title = "Enhancer elements upstream of the SHOX gene are active in the developing limb",
abstract = "Leri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.",
keywords = "enhancer, Leri-Weill dyschondrosteosis, homeobox gene, SHOX, short stature",
author = "C Durand and Fiona Bangs and Jason Signolet and E Decker and Cheryll Tickle and G Rappold",
year = "2010",
month = "5",
doi = "10.1038/ejhg.2009.216",
language = "English",
volume = "18",
pages = "527--532",
journal = "European Journal of Human Genetics",
issn = "1018-4813",
publisher = "Nature Research",
number = "5",

}

TY - JOUR

T1 - Enhancer elements upstream of the SHOX gene are active in the developing limb

AU - Durand, C

AU - Bangs, Fiona

AU - Signolet, Jason

AU - Decker, E

AU - Tickle, Cheryll

AU - Rappold, G

PY - 2010/5

Y1 - 2010/5

N2 - Leri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.

AB - Leri-Weill Dyschondrosteosis (LWD) is a dominant skeletal disorder characterized by short stature and distinct bone anomalies. SHOX gene mutations and deletions of regulatory elements downstream of SHOX resulting in haploinsufficiency have been found in patients with LWD. SHOX encodes a homeodomain transcription factor and is known to be expressed in the developing limb. We have now analyzed the regulatory significance of the region upstream of the SHOX gene. By comparative genomic analyses, we identified several conserved non-coding elements, which subsequently were tested in an in ovo enhancer assay in both chicken limb bud and cornea, where SHOX is also expressed. In this assay, we found three enhancers to be active in the developing chicken limb, but none were functional in the developing cornea. A screening of 60 LWD patients with an intact SHOX coding and downstream region did not yield any deletion of the upstream enhancer region. Thus, we speculate that SHOX upstream deletions occur at a lower frequency because of the structural organization of this genomic region and/or that SHOX upstream deletions may cause a phenotype that differs from the one observed in LWD.

KW - enhancer

KW - Leri-Weill dyschondrosteosis

KW - homeobox gene

KW - SHOX

KW - short stature

UR - http://www.scopus.com/inward/record.url?scp=77951621736&partnerID=8YFLogxK

UR - http://dx.doi.org/10.1038/ejhg.2009.216

U2 - 10.1038/ejhg.2009.216

DO - 10.1038/ejhg.2009.216

M3 - Article

VL - 18

SP - 527

EP - 532

JO - European Journal of Human Genetics

JF - European Journal of Human Genetics

SN - 1018-4813

IS - 5

ER -