Affiliations: [a] Section of Hematology-Oncology, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA | [b] Department of Epidemiology, Human Genetics and Environmental Sciences, UTHealth School of Public Health, Houston, TX, USA | [c] Section of Developmental Pediatrics, Department of Pediatrics, Baylor College of Medicine, Houston, TX, USA | [d] Department of Physical Medicine and Rehabilitation, Children’s Hospital Colorado, Aurora, CO, USA | [e] Department of Pediatrics, Center for Development Behavior and Genetics, State University of New York Upstate Medical University, Syracuse, NY, USA | [f] Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, AL, USA | [g] Department of Urology, University of Alabama at Birmingham, Birmingham, AL, USA | [h] Division of Developmental Medicine, Seattle Children’s Hospital, Seattle, WA, USA | [i] Division of Urology, Duke University Medical Center, Durham, NC, USA
Corresponding author: Philip J. Lupo, One Baylor Plaza, MS: BCM305, Houston, TX 77030, USA. Tel.: +1 713 798 2960; E-mail: [email protected]
Abstract: It has been estimated that 60–70% of neural tube defects (NTDs) have a genetic component, but few causative genes have been identified. The lack of information on genes associated with non-syndromic NTDs in humans is especially notable as the “genomic revolution” has led to new tools (e.g., genome-wide genotyping arrays, next-generation sequencing) that are helping to elucidate the full spectrum of genetic variation (from common to rare) contributing to complex traits, including structural birth defects. However, the application of modern genomic approaches to the study of NTDs has lagged behind that of some other common structural birth defects. This may be due to the difficulty of assembling large study cohorts for anencephaly or spina bifida. The purpose of this review is to outline the evolution of genetic studies of NTDs, from studies of familial aggregation to candidate gene and genome-wide association studies, through whole-exome and whole-genome sequencing. Strategies for addressing gaps in NTD genetic research are also explored.
Keywords: Epidemiology, genetics, human studies, neural tube defects, spina bifida