@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.}",
note = "Funding Information: We thank patients, their families, and clinicians for their contribution and cooperation; D. Chapman, S. Mansour, G. Martin, T. Vogt, and K. Willert for plasmids; K. Hozumi, R. Kopan, S. Piccolo, and P. Tam for mouse lines; E. Thompson and C. Barnett for assessment of family B; BioCORE staff, L. Tomlinson, S. Goettl, J.-S. Han, L. Lunny, and M. Maisenbacher for technical assistance; Herbert Smith for donating the confocal microscopes used in this study; and R. Harvey and K. Anderson for comments on the text. Work was supported by National Health and Medical Research Council Project grant 635500 (S.L.D. and D.B.S.); NHMRC Senior Research Fellowship 514900 (S.L.D.); a Westfield-Belconnen Fellowship (D.B.S.); and a Hitchings-Elion Fellowship of the Burroughs Wellcome Fund, Cervical Spine Research Society, Ethel Brown Foerderer Fund for Excellence and Florence R.C. Murray Fund (K.K.). D.B.S. dedicates this article to David Sparrow (December 11, 1927–March 22, 2012) an inspiring geneticist and loving father. ",
year = "2012",
month = apr,
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",
}