A mechanism for gene-environment interaction in the etiology of congenital scoliosis

Duncan B. Sparrow, Gavin Chapman, Allanceson J. Smith, Muhammad Z. Mattar, Joelene A. Major, Victoria C. O'Reilly, Yumiko Saga, Elaine H. Zackai, John P. Dormans, Benjamin A. Alman, Lesley McGregor, Ryoichiro Kageyama, Kenro Kusumi, Sally L. Dunwoodie

Research output: Contribution to journalArticle

102 Citations (Scopus)

Abstract

Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.

Original languageEnglish (US)
Pages (from-to)295-306
Number of pages12
JournalCell
Volume149
Issue number2
DOIs
StatePublished - Apr 13 2012

Fingerprint

Gene-Environment Interaction
Scoliosis
Genes
Haploinsufficiency
Defects
Penetrance
Genetic Models
Live Birth
Spine
Hypoxia

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Sparrow, D. B., Chapman, G., Smith, A. J., Mattar, M. Z., Major, J. A., O'Reilly, V. C., ... Dunwoodie, S. L. (2012). A mechanism for gene-environment interaction in the etiology of congenital scoliosis. Cell, 149(2), 295-306. https://doi.org/10.1016/j.cell.2012.02.054

A mechanism for gene-environment interaction in the etiology of congenital scoliosis. / Sparrow, Duncan B.; Chapman, Gavin; Smith, Allanceson J.; Mattar, Muhammad Z.; Major, Joelene A.; O'Reilly, Victoria C.; Saga, Yumiko; Zackai, Elaine H.; Dormans, John P.; Alman, Benjamin A.; McGregor, Lesley; Kageyama, Ryoichiro; Kusumi, Kenro; Dunwoodie, Sally L.

In: Cell, Vol. 149, No. 2, 13.04.2012, p. 295-306.

Research output: Contribution to journalArticle

Sparrow, DB, Chapman, G, Smith, AJ, Mattar, MZ, Major, JA, O'Reilly, VC, Saga, Y, Zackai, EH, Dormans, JP, Alman, BA, McGregor, L, Kageyama, R, Kusumi, K & Dunwoodie, SL 2012, 'A mechanism for gene-environment interaction in the etiology of congenital scoliosis', Cell, vol. 149, no. 2, pp. 295-306. https://doi.org/10.1016/j.cell.2012.02.054
Sparrow DB, Chapman G, Smith AJ, Mattar MZ, Major JA, O'Reilly VC et al. A mechanism for gene-environment interaction in the etiology of congenital scoliosis. Cell. 2012 Apr 13;149(2):295-306. https://doi.org/10.1016/j.cell.2012.02.054
Sparrow, Duncan B. ; Chapman, Gavin ; Smith, Allanceson J. ; Mattar, Muhammad Z. ; Major, Joelene A. ; O'Reilly, Victoria C. ; Saga, Yumiko ; Zackai, Elaine H. ; Dormans, John P. ; Alman, Benjamin A. ; McGregor, Lesley ; Kageyama, Ryoichiro ; Kusumi, Kenro ; Dunwoodie, Sally L. / A mechanism for gene-environment interaction in the etiology of congenital scoliosis. In: Cell. 2012 ; Vol. 149, No. 2. pp. 295-306.
@article{bc80e74f3b0e47409ebbe8415756aba5,
title = "A mechanism for gene-environment interaction in the etiology of congenital scoliosis",
abstract = "Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.",
author = "Sparrow, {Duncan B.} and Gavin Chapman and Smith, {Allanceson J.} and Mattar, {Muhammad Z.} and Major, {Joelene A.} and O'Reilly, {Victoria C.} and Yumiko Saga and Zackai, {Elaine H.} and Dormans, {John P.} and Alman, {Benjamin A.} and Lesley McGregor and Ryoichiro Kageyama and Kenro Kusumi and Dunwoodie, {Sally L.}",
year = "2012",
month = "4",
day = "13",
doi = "10.1016/j.cell.2012.02.054",
language = "English (US)",
volume = "149",
pages = "295--306",
journal = "Cell",
issn = "0092-8674",
publisher = "Cell Press",
number = "2",

}

TY - JOUR

T1 - A mechanism for gene-environment interaction in the etiology of congenital scoliosis

AU - Sparrow, Duncan B.

AU - Chapman, Gavin

AU - Smith, Allanceson J.

AU - Mattar, Muhammad Z.

AU - Major, Joelene A.

AU - O'Reilly, Victoria C.

AU - Saga, Yumiko

AU - Zackai, Elaine H.

AU - Dormans, John P.

AU - Alman, Benjamin A.

AU - McGregor, Lesley

AU - Kageyama, Ryoichiro

AU - Kusumi, Kenro

AU - Dunwoodie, Sally L.

PY - 2012/4/13

Y1 - 2012/4/13

N2 - Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.

AB - Congenital scoliosis, a lateral curvature of the spine caused by vertebral defects, occurs in approximately 1 in 1,000 live births. Here we demonstrate that haploinsufficiency of Notch signaling pathway genes in humans can cause this congenital abnormality. We also show that in a mouse model, the combination of this genetic risk factor with an environmental condition (short-term gestational hypoxia) significantly increases the penetrance and severity of vertebral defects. We demonstrate that hypoxia disrupts FGF signaling, leading to a temporary failure of embryonic somitogenesis. Our results potentially provide a mechanism for the genesis of a host of common sporadic congenital abnormalities through gene-environment interaction.

UR - http://www.scopus.com/inward/record.url?scp=84859753758&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84859753758&partnerID=8YFLogxK

U2 - 10.1016/j.cell.2012.02.054

DO - 10.1016/j.cell.2012.02.054

M3 - Article

C2 - 22484060

AN - SCOPUS:84859753758

VL - 149

SP - 295

EP - 306

JO - Cell

JF - Cell

SN - 0092-8674

IS - 2

ER -