A Mechanism for Gene-Environment Interaction in the Etiology of Congenital Scoliosis
نویسندگان
چکیده
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.
منابع مشابه
Etiology of Congenital Scoliosis
Congenital scoliosis is an abnormal lateral curvature of the spine, resulting from disruption of normal vertebral development. Although there are many types of defects observed in congenital scoliosis, all result from abnormal formation and segmentation of the vertebral precursors, called somites. Developmental studies in animal models have identified many genes regulating somite formation and ...
متن کاملمقایسه نتایج کوتاه مدت و بلند مدت فیوژن ستون مهرهها با و بدون وسیلهگذاری خلفی در درمان اسکولیوز مادرزادی
Background: Congenital scoliosis is a developmental disorder defined as a lateral curvature of the spine. Its progressive trend and complications, such as cosmetic problems, pain and pulmonary symptoms, have put scoliosis as an important skeletal deformity that should be corrected. One of the currently accepted methods of treatment is posterior spinal fusion (PSF) that may be performed with or ...
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Congenital scoliosis due to vertebral anomalies may occur in less than 0.1% of the population. Several different theories have been put forth in the literature to account for the etiology of congenital scoliosis and the vertebral anomalies which contribute to its development. The study of scoliosis in twins has contributed to the understanding of causative factors including genetics, environmen...
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A common study to investigate gene-environment interaction is designed to be longitudinal and population-based. Data arising from longitudinal association studies often contain missing responses. Naive analysis without taking missingness into account may produce invalid inference, especially when the missing data mechanism depends on the response process. To address this issue in the ana...
متن کاملCongenital scoliosis in monozygotic twins: case report and review of possible factors contributing to its development
BACKGROUND The exact etiology of congenital scoliosis remains unknown as yet. It seems that its development may be influenced by both genetic predisposition and environmental factors, at varying degrees. International bibliography features few cases of monozygotic twins with congenital scoliosis. The aim of this study is to report a case in monozygotic twins and review the literature relating t...
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عنوان ژورنال:
- Cell
دوره 149 شماره
صفحات -
تاریخ انتشار 2012