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Exploring Shared Susceptibility between Two Neural Crest Cells Originating Conditions: Neuroblastoma and Congenital Heart Disease

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Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, 80131 Naples, Italy
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CEINGE Biotecnologie Avanzate, 80145 Naples, Italy
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IRCCS SDN, Istituto di Ricerca Diagnostica e Nucleare, 80143 Naples, Italy
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Division of Cardiology, Università degli Studi della Campania “Luigi Vanvitelli” - AO dei Colli, Presidio Monaldi, 80121 Naples, Italy
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Division of Oncology and Center for Childhood Cancer Research, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Division of Genetics, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA
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Department of Translational and Precision Medicine, University of Rome “La Sapienza”, 00185 Rome, Italy
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Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
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Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester M13 9PL, UK
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Manchester University NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester M20 4BX, UK
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Institute of Genetic Medicine, Newcastle University, Central Parkway, Newcastle upon Tyne NE1 3BZ, UK
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Author to whom correspondence should be addressed.
Genes 2019, 10(9), 663; https://doi.org/10.3390/genes10090663
Received: 7 May 2019 / Revised: 12 August 2019 / Accepted: 26 August 2019 / Published: 30 August 2019
(This article belongs to the Section Human Genomics and Genetic Diseases)
In the past years, genome wide association studies (GWAS) have provided evidence that inter-individual susceptibility to diverse pathological conditions can reveal a common genetic architecture. Through the analysis of congenital heart disease (CHD) and neuroblastoma (NB) GWAS data, we aimed to dissect the genetic susceptibility shared between these conditions, which are known to arise from neural crest cell (NCC) migration or development abnormalities, via identification and functional characterization of common regions of association. Two loci (2q35 and 3q25.32) harbor single nucleotide polymorphisms (SNPs) that are associated at a p-value < 10−3 with conotruncal malformations and ventricular septal defect respectively, as well as with NB. In addition, the lead SNP in 4p16.2 for atrial septal defect and the lead SNP in 3q25.32 for tetralogy of Fallot are less than 250 Kb distant from the lead SNPs for NB at the same genomic regions. Some of these shared susceptibility loci regulate the expression of relevant genes involved in NCC formation and developmental processes (such as BARD1, MSX1, and SHOX2) and are enriched in several epigenetic markers from NB and fetal heart cell lines. Although the clinical correlation between NB and CHD is unclear, our exploration of a possible common genetic basis between NB and a subset of cardiac malformations can help shed light on their shared embryological origin and pathogenetic mechanisms. View Full-Text
Keywords: genome wide association studies; neuroblastoma; congenital heart disease genome wide association studies; neuroblastoma; congenital heart disease
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Testori, A.; Lasorsa, V.A.; Cimmino, F.; Cantalupo, S.; Cardinale, A.; Avitabile, M.; Limongelli, G.; Russo, M.G.; Diskin, S.; Maris, J.; Devoto, M.; Keavney, B.; Cordell, H.J.; Iolascon, A.; Capasso, M. Exploring Shared Susceptibility between Two Neural Crest Cells Originating Conditions: Neuroblastoma and Congenital Heart Disease. Genes 2019, 10, 663.

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