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A cis-regulatory-directed pipeline for the identification of genes involved in cardiac development and disease.
Nim, Hieu T; Dang, Louis; Thiyagarajah, Harshini; Bakopoulos, Daniel; See, Michael; Charitakis, Natalie; Sibbritt, Tennille; Eichenlaub, Michael P; Archer, Stuart K; Fossat, Nicolas; Burke, Richard E; Tam, Patrick P L; Warr, Coral G; Johnson, Travis K; Ramialison, Mirana.
Afiliación
  • Nim HT; Australian Regenerative Medicine Institute and Systems Biology Institute Australia, Monash University, Clayton, VIC, Australia.
  • Dang L; Murdoch Children's Research Institute, Parkville, VIC, Australia.
  • Thiyagarajah H; Australian Regenerative Medicine Institute and Systems Biology Institute Australia, Monash University, Clayton, VIC, Australia.
  • Bakopoulos D; School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia.
  • See M; School of Biological Sciences, Faculty of Science, Monash University, Clayton, VIC, Australia.
  • Charitakis N; Murdoch Children's Research Institute, Parkville, VIC, Australia.
  • Sibbritt T; Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia.
  • Eichenlaub MP; Murdoch Children's Research Institute, Parkville, VIC, Australia.
  • Archer SK; Department of Paediatrics, University of Melbourne, Parkville, VIC, Australia.
  • Fossat N; Embryology Research Unit, Children's Medical Research Institute, and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead, New South Wales, Australia.
  • Burke RE; Australian Regenerative Medicine Institute and Systems Biology Institute Australia, Monash University, Clayton, VIC, Australia.
  • Tam PPL; Monash Bioinformatics Platform, Monash University, Clayton, VIC, Australia.
  • Warr CG; Embryology Research Unit, Children's Medical Research Institute, and School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead, New South Wales, Australia.
  • Johnson TK; Present address: Copenhagen Hepatitis C Program, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark.
  • Ramialison M; Present address: Department of Infectious Diseases, Hvidovre Hospital, Hvidovre, Denmark.
Genome Biol ; 22(1): 335, 2021 12 15.
Article en En | MEDLINE | ID: mdl-34906219
BACKGROUND: Congenital heart diseases are the major cause of death in newborns, but the genetic etiology of this developmental disorder is not fully known. The conventional approach to identify the disease-causing genes focuses on screening genes that display heart-specific expression during development. However, this approach would have discounted genes that are expressed widely in other tissues but may play critical roles in heart development. RESULTS: We report an efficient pipeline of genome-wide gene discovery based on the identification of a cardiac-specific cis-regulatory element signature that points to candidate genes involved in heart development and congenital heart disease. With this pipeline, we retrieve 76% of the known cardiac developmental genes and predict 35 novel genes that previously had no known connectivity to heart development. Functional validation of these novel cardiac genes by RNAi-mediated knockdown of the conserved orthologs in Drosophila cardiac tissue reveals that disrupting the activity of 71% of these genes leads to adult mortality. Among these genes, RpL14, RpS24, and Rpn8 are associated with heart phenotypes. CONCLUSIONS: Our pipeline has enabled the discovery of novel genes with roles in heart development. This workflow, which relies on screening for non-coding cis-regulatory signatures, is amenable for identifying developmental and disease genes for an organ without constraining to genes that are expressed exclusively in the organ of interest.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación del Desarrollo de la Expresión Génica / Corazón / Cardiopatías Congénitas Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Regulación del Desarrollo de la Expresión Génica / Corazón / Cardiopatías Congénitas Tipo de estudio: Diagnostic_studies Límite: Animals Idioma: En Revista: Genome Biol Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2021 Tipo del documento: Article País de afiliación: Australia Pais de publicación: Reino Unido