Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development
Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients h...
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| Veröffentlicht in: | PLoS genetics 2021-08, Vol.17 (8), p.e1009698-e1009698 |
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| creator | Kuil, Laura E MacKenzie, Katherine C Tang, Clara S Windster, Jonathan D Le, Thuy Linh Karim, Anwarul de Graaf, Bianca M van der Helm, Robert van Bever, Yolande Sloots, Cornelius E. J Meeussen, Conny Tibboel, Dick de Klein, Annelies Wijnen, René M. H Amiel, Jeanne Lyonnet, Stanislas Garcia-Barcelo, Maria-Mercè Tam, Paul K. H Alves, Maria M Brooks, Alice S Hofstra, Robert M. W Brosens, Erwin |
| description | Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. Next, we used a zebrafish model to investigate whether loss of these genes affects enteric neuron development in vivo. |
| doi_str_mv | 10.1371/journal.pgen.1009698 |
| format | Article |
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J ; Meeussen, Conny ; Tibboel, Dick ; de Klein, Annelies ; Wijnen, René M. H ; Amiel, Jeanne ; Lyonnet, Stanislas ; Garcia-Barcelo, Maria-Mercè ; Tam, Paul K. H ; Alves, Maria M ; Brooks, Alice S ; Hofstra, Robert M. W ; Brosens, Erwin</creator><contributor>Barsh, Gregory S.</contributor><creatorcontrib>Kuil, Laura E ; MacKenzie, Katherine C ; Tang, Clara S ; Windster, Jonathan D ; Le, Thuy Linh ; Karim, Anwarul ; de Graaf, Bianca M ; van der Helm, Robert ; van Bever, Yolande ; Sloots, Cornelius E. J ; Meeussen, Conny ; Tibboel, Dick ; de Klein, Annelies ; Wijnen, René M. H ; Amiel, Jeanne ; Lyonnet, Stanislas ; Garcia-Barcelo, Maria-Mercè ; Tam, Paul K. H ; Alves, Maria M ; Brooks, Alice S ; Hofstra, Robert M. W ; Brosens, Erwin ; Barsh, Gregory S.</creatorcontrib><description>Hirschsprung disease (HSCR) is a complex genetic disease characterized by absence of ganglia in the intestine. HSCR etiology can be explained by a unique combination of genetic alterations: rare coding variants, predisposing haplotypes and Copy Number Variation (CNV). Approximately 18% of patients have additional anatomical malformations or neurological symptoms (HSCR-AAM). Pinpointing the responsible culprits within a CNV is challenging as often many genes are affected. Therefore, we selected candidate genes based on gene enrichment strategies using mouse enteric nervous system transcriptomes and constraint metrics. 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| ispartof | PLoS genetics, 2021-08, Vol.17 (8), p.e1009698-e1009698 |
| issn | 1553-7404 1553-7390 1553-7404 |
| language | eng |
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| source | DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Biology and Life Sciences Coding Congenital diseases Copy number Copy number variations CRISPR Cystic fibrosis Danio rerio Disease Enteric nervous system Epistasis Etiology Ganglia Gene expression Genetic aspects Genomes Haplotypes Health aspects Health risk assessment Hirschsprung's disease Intestine Intestine, Small Medicine and Health Sciences Mutation Nervous system Nervous system, Autonomic Neural coding Patients Research and Analysis Methods Transcriptomes |
| title | Size matters: Large copy number losses in Hirschsprung disease patients reveal genes involved in enteric nervous system development |
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