Biliary-Atresia-Associated Mannosidase-1-Alpha-2 Gene Regulates Biliary and Ciliary Morphogenesis and Laterality.

biliary atresia biliary morphogenesis cilia laterality liver transplantation

Journal

Frontiers in physiology
ISSN: 1664-042X
Titre abrégé: Front Physiol
Pays: Switzerland
ID NLM: 101549006

Informations de publication

Date de publication:
2020
Historique:
received: 03 06 2020
accepted: 23 09 2020
entrez: 16 11 2020
pubmed: 17 11 2020
medline: 17 11 2020
Statut: epublish

Résumé

Infectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins. We investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype. Candidate gene effects on morphogenesis, developmental pathways, and ciliogenesis, which regulates left-right patterning were investigated with zebrafish knockdown and mouse knockout models, mouse airway cell cultures, and liver transcriptome analysis. Single nucleotide polymorphisms in Mannosidase-1-α-2 ( BA requiring transplantation associates with sequence variants in

Sections du résumé

BACKGROUND/AIMS OBJECTIVE
Infectious and genetic factors are invoked, respectively in isolated biliary atresia (BA), or syndromic BA, with major extrahepatic anomalies. However, isolated BA is also associated with minor extrahepatic gut and cardiovascular anomalies and multiple susceptibility genes, suggesting common origins.
METHODS METHODS
We investigated novel susceptibility genes with genome-wide association, targeted sequencing and tissue staining in BA requiring liver transplantation, independent of BA subtype. Candidate gene effects on morphogenesis, developmental pathways, and ciliogenesis, which regulates left-right patterning were investigated with zebrafish knockdown and mouse knockout models, mouse airway cell cultures, and liver transcriptome analysis.
RESULTS RESULTS
Single nucleotide polymorphisms in Mannosidase-1-α-2 (
CONCLUSION CONCLUSIONS
BA requiring transplantation associates with sequence variants in

Identifiants

pubmed: 33192543
doi: 10.3389/fphys.2020.538701
pmc: PMC7662016
doi:

Types de publication

Journal Article

Langues

eng

Pagination

538701

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK101426
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK109365
Pays : United States

Informations de copyright

Copyright © 2020 So, Ningappa, Glessner, Min, Ashokkumar, Ranganathan, Higgs, Li, Sun, Schmitt, Biery, Dobrowolski, Trautz, Fuhrman, Schwartz, Klena, Fusco, Prasadan, Adenuga, Mohamed, Yan, Chen, Horne, Dhawan, Sharif, Kelly, Squires, Gittes, Hakonarson, Morell, Lo, Subramaniam, Shin and Sindhi.

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Auteurs

Juhoon So (J)

Department of Developmental Biology, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

Mylarappa Ningappa (M)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Joseph Glessner (J)

Center for Applied Genomics of the Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Jun Min (J)

Departments of Bioengineering, Cellular and Molecular Medicine, and Computer Science and Engineering, University of California San Diego, La Jolla, CA, United States.

Chethan Ashokkumar (C)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Sarangarajan Ranganathan (S)

Division of Pediatric Pathology, Department of Pathology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Brandon W Higgs (BW)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Dong Li (D)

Center for Applied Genomics of the Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Qing Sun (Q)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Lori Schmitt (L)

Histology Core Laboratory, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Amy C Biery (AC)

Division of Pediatric Pathology, Department of Pathology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Steven Dobrowolski (S)

Division of Pediatric Pathology, Department of Pathology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Christine Trautz (C)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Leah Fuhrman (L)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Molly Christine Schwartz (MC)

Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States.

Nikolai Thomas Klena (NT)

Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States.

Joseph Fusco (J)

Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Krishna Prasadan (K)

Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Morayooluwa Adenuga (M)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Nada Mohamed (N)

Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Qi Yan (Q)

Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.

Wei Chen (W)

Departments of Human Genetics and Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, United States.

William Horne (W)

Richard King Mellon Foundation Institute for Pediatric Research, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Anil Dhawan (A)

Paediatric Liver, GI, and Nutrition, King's College Hospital, London, United Kingdom.

Khalid Sharif (K)

Children's Hospital of Birmingham, Birmingham, United Kingdom.

Deirdre Kelly (D)

Children's Hospital of Birmingham, Birmingham, United Kingdom.

Robert H Squires (RH)

Pediatric Gastroenterology, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

George K Gittes (GK)

Pediatric General and Thoracic Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Hakon Hakonarson (H)

Center for Applied Genomics of the Children's Hospital of Philadelphia, Philadelphia, PA, United States.

Victor Morell (V)

Division of Cardiac Surgery, Department of Cardiothoracic Surgery, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA, United States.

Cecilia Lo (C)

Department of Developmental Biology, University of Pittsburgh, Pittsburgh, PA, United States.

Shankar Subramaniam (S)

Departments of Bioengineering, Cellular and Molecular Medicine, and Computer Science and Engineering, University of California San Diego, La Jolla, CA, United States.

Donghun Shin (D)

Department of Developmental Biology, McGowan Institute of Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA, United States.

Rakesh Sindhi (R)

Hillman Center for Pediatric Transplantation of the Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center (UPMC), Pittsburgh, PA, United States.

Classifications MeSH