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 journalArticlepeer-review

175 Scopus citations


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
Issue number2
StatePublished - Apr 13 2012

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


Dive into the research topics of 'A mechanism for gene-environment interaction in the etiology of congenital scoliosis'. Together they form a unique fingerprint.

Cite this