title: Xenopus as a model organism for birth defects-Congenital heart disease and heterotaxy.
abstract: Congenital heart disease is the leading cause of birth defects, affecting 9 out of 1000 newborns each year. A particularly severe form of congenital heart disease is heterotaxy, a disorder of left-right development. Despite aggressive surgical management, patients with heterotaxy have poor survival rates and severe morbidity due to their complex congenital heart disease. Recent genetic analysis of affected patients has found novel candidate genes for heterotaxy although their underlying mechanisms remain unknown. In this review, we discuss the importance and challenges of birth defects research including high locus heterogeneity and few second alleles that make defining disease causality difficult. A powerful strategy moving forward is to analyze these candidate genes in a high-throughput human disease model. Xenopus is ideal for these studies. We present multiple examples demonstrating the power of Xenopus in discovering new biology from the analysis of candidate heterotaxy genes such as GALNT11, NEK2 and BCOR. These genes have diverse roles in embryos and have led to a greater understanding of complex signaling pathways and basic developmental biology. It is our hope that the mechanistic analysis of these candidate genes in Xenopus enabled by next generation sequencing of patients will provide clinicians with a greater understanding of patient pathophysiology allowing more precise and personalized medicine, to help patients more effectively in the future.
authors.affiliation: Department of Pediatrics, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, United States.
authors.forename: Anna R
authors.initials: AR
authors.lastname: Duncan
authors.affiliation: Department of Pediatrics and Genetics, Yale University School of Medicine, 333 Cedar St, New Haven, CT 06520, United States. Electronic address: mustafa.khokha@yale.edu.
authors.forename: Mustafa K
authors.initials: MK
authors.lastname: Khokha
mesh_terms: D000818:Animals; D019521:Body Patterning; D004195:Disease Models, Animal; D059446:Heterotaxy Syndrome / Q000235:genetics*; D006801:Humans; D009154:Mutation; D017350:N-Acetylgalactosaminyltransferases / Q000235:genetics; D000072379:NIMA-Related Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D014981:Xenopus / Q000235:genetics / Q000254:growth & development*; D029867:Xenopus Proteins / Q000235:genetics
chemical_list: C411984:BCOR protein, human; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; D029867:Xenopus Proteins; C553205:GALNT11 protein, human; D017350:N-Acetylgalactosaminyltransferases; C089441:NEK2 protein, human; D000072379:NIMA-Related Kinases
keywords: BCOR; Congenital heart disease; Disease model; Heterotaxy; Human genetics; Xenopus; galnt11; nek2