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Birth Defects Res A Clin Mol Teratol. 2015 Aug;103(8):680-91. doi: 10.1002/bdra.23385. Epub 2015 May 28.

Developments in our understanding of the genetic basis of birth defects.

Author information

Division of Birth Defects Research, Department of Pediatrics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Division of Genetic Medicine, Department of Pediatrics, University of Washington, Seattle, Washington.
Stanford University School of Medicine, Stanford, California.
Dell Pediatric Research Institute, Department of Nutritional Sciences, The University of Texas at Austin, Austin, Texas.
Department of Epidemiology, MD Anderson Cancer Center, Houston, Texas.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, California.
Department of Biostatistics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas.


Birth defects are a major cause of morbidity and mortality worldwide. There has been much progress in understanding the genetic basis of familial and syndromic forms of birth defects. However, the etiology of nonsydromic birth defects is not well-understood. Although there is still much work to be done, we have many of the tools needed to accomplish the task. Advances in next-generation sequencing have introduced a sea of possibilities, from disease-gene discovery to clinical screening and diagnosis. These advances have been fruitful in identifying a host of candidate disease genes, spanning the spectrum of birth defects. With the advent of CRISPR-Cas9 gene editing, researchers now have a precise tool for characterizing this genetic variation in model systems. Work in model organisms has also illustrated the importance of epigenetics in human development and birth defects etiology. Here we review past and current knowledge in birth defects genetics. We describe genotyping and sequencing methods for the detection and analysis of rare and common variants. We remark on the utility of model organisms and explore epigenetics in the context of structural malformation. We conclude by highlighting approaches that may provide insight into the complex genetics of birth defects.


Birth defects; cleft lip and palate; congenital heart defects; epigenetics; genetics; hypospadias; neural tube defects; next-generation sequencing

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