a genetic signature of spina bifida risk from pathway-informed comprehensive gene-variant analysis脊柱裂风险的基因签名pathway-informed综合基因变异分析.pdfVIP

A Genetic Signature of Spina Bifida Risk from Pathway- Informed Comprehensive Gene-Variant Analysis 1 2 3 4 4 Nicholas J. Marini *, Thomas J. Hoffmann , Edward J. Lammer , Jill Hardin , Katherine Lazaruk , Jason B. 4 4 5 5 5 6 Stein , Dennis A. Gilbert , Crystal Wright , Anna Lipzen , Len A. Pennacchio , Suzan L. Carmichael , 2 6 1 John S. Witte , Gary M. Shaw , Jasper Rine * 1 Department of Molecular and Cellular Biology, California Institute for Quantitative Biosciences, University of California, Berkeley, California, United States of America, 2 Department of Epidemiology and Biostatistics and Institute of Human Genetics, University of California San Francisco, San Francisco, California, United States of America, 3 Children’s Hospital Oakland Research Institute, Oakland, California, United States of America, 4 VitaPath Genetics, Inc., Foster City, California, United States of America, 5 Department of Energy, Joint Genome Institute, Walnut Creek, California, United States of America, 6 Department of Pediatrics, Stanford University School of Medicine, Stanford, California, United States of America Abstract Despite compelling epidemiological evidence that folic acid supplements reduce the frequency of neural tube defects (NTDs) in newborns, common variant association studies with folate metabolism genes have failed to explain the majority of NTD risk. The contribution of rare alleles as well as genetic interactions within the folate pathway have not been extensively studied in the context of NTDs. Thus, we sequenced the exons in 31 folate-related