التفاصيل البيبلوغرافية
| العنوان: |
The Role of Cilia and the Complex Genetics of Congenital Heart Disease. |
| المؤلفون: |
Gabriel GC; Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email: gcg9@pitt.edu, cel36@pitt.edu., Ganapathiraju M; Carnegie Mellon University in Qatar, Doha, Qatar.; Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email: madhavi@pitt.edu., Lo CW; Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email: gcg9@pitt.edu, cel36@pitt.edu. |
| المصدر: |
Annual review of genomics and human genetics [Annu Rev Genomics Hum Genet] 2024 Aug; Vol. 25 (1), pp. 309-327. Date of Electronic Publication: 2024 Aug 06. |
| نوع المنشور: |
Journal Article; Review |
| اللغة: |
English |
| بيانات الدورية: |
Publisher: Annual Reviews Country of Publication: United States NLM ID: 100911346 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1545-293X (Electronic) Linking ISSN: 15278204 NLM ISO Abbreviation: Annu Rev Genomics Hum Genet Subsets: MEDLINE |
| أسماء مطبوعة: |
Original Publication: Palo Alto, CA : Annual Reviews, c2000- |
| مواضيع طبية MeSH: |
Cilia*/pathology , Cilia*/genetics , Cilia*/metabolism , Heart Defects, Congenital*/genetics , Heart Defects, Congenital*/pathology, Humans ; Animals ; Mice ; Mutation ; Signal Transduction ; Protein Interaction Maps |
| مستخلص: |
Congenital heart disease (CHD) can affect up to 1% of live births, and despite abundant evidence of a genetic etiology, the genetic landscape of CHD is still not well understood. A large-scale mouse chemical mutagenesis screen for mutations causing CHD yielded a preponderance of cilia-related genes, pointing to a central role for cilia in CHD pathogenesis. The genes uncovered by the screen included genes that regulate ciliogenesis and cilia-transduced cell signaling as well as many that mediate endocytic trafficking, a cell process critical for both ciliogenesis and cell signaling. The clinical relevance of these findings is supported by whole-exome sequencing analysis of CHD patients that showed enrichment for pathogenic variants in ciliome genes. Surprisingly, among the ciliome CHD genes recovered were many that encoded direct protein-protein interactors. Assembly of the CHD genes into a protein-protein interaction network yielded a tight interactome that suggested this protein-protein interaction may have functional importance and that its disruption could contribute to the pathogenesis of CHD. In light of these and other findings, we propose that an interactome enriched for ciliome genes may provide the genomic context for the complex genetics of CHD and its often-observed incomplete penetrance and variable expressivity. |
| فهرسة مساهمة: |
Keywords: cilia; complex genetics; congenital heart disease |
| تواريخ الأحداث: |
Date Created: 20240509 Date Completed: 20240827 Latest Revision: 20240827 |
| رمز التحديث: |
20240828 |
| DOI: |
10.1146/annurev-genom-121222-105345 |
| PMID: |
38724024 |
| قاعدة البيانات: |
MEDLINE |
