The Role of Cilia and the Complex Genetics of Congenital Heart Disease
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,...
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| Published in | Annual review of genomics and human genetics Vol. 25; no. 1; pp. 309 - 327 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
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01.08.2024
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| Abstract | 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. |
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| AbstractList | 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. 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.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. |
| Author | Gabriel, George C Lo, Cecilia W Ganapathiraju, Madhavi |
| AuthorAffiliation | 1 gcg9@pitt.edu 2 3 Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email Carnegie Mellon University in Qatar, Doha, Qatar Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email cel36@pitt.edu madhavi@pitt.edu , |
| AuthorAffiliation_xml | – name: – name: 3 – name: Department of Developmental Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email – name: gcg9@pitt.edu – name: cel36@pitt.edu – name: Department of Biomedical Informatics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; email – name: , – name: 2 – name: madhavi@pitt.edu – name: 1 – name: Carnegie Mellon University in Qatar, Doha, Qatar |
| Author_xml | – sequence: 1 givenname: George C surname: Gabriel fullname: Gabriel, George C – sequence: 2 givenname: Madhavi surname: Ganapathiraju fullname: Ganapathiraju, Madhavi – sequence: 3 givenname: Cecilia W surname: Lo fullname: Lo, Cecilia W |
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| Cites_doi | 10.1091/mbc.e08-08-0805 10.1016/S0735-1097(02)01886-7 10.1038/ng.3870 10.1007/s00431-010-1200-0 10.3390/biom12060847 10.1093/nar/gkn892 10.1038/s41572-020-0209-6 10.1073/pnas.2218819120 10.1016/S0735-1097(98)00259-9 10.1038/ng.2681 10.1111/chd.12413 10.1038/nature14670 10.1038/gim.2017.94 10.1186/s13630-016-0035-3 10.1016/j.ejmg.2012.07.010 10.1038/s41588-020-0707-1 10.1016/j.jpeds.2018.08.068 10.4161/org.27483 10.1038/ncomms7023 10.1016/j.xcrm.2021.100501 10.1016/j.ajhg.2008.10.002 10.1007/s00018-017-2570-5 10.1038/gim.2016.167 10.1038/nrm.2017.60 10.1161/CIRCULATIONAHA.119.038376 10.3389/fped.2018.00175 10.1093/nar/gky1079 10.1016/0735-1097(89)90122-8 10.1161/CIRCIMAGING.113.000451 10.1016/j.bbrc.2009.03.113 10.1126/scitranslmed.aax0290 10.1038/ng.3558 10.1161/CIRCULATIONAHA.123.064400 10.1038/ng.3376 10.1161/CIR.0b013e318265ee8a 10.3390/genes13040627 10.1161/CIRCULATIONAHA.110.946343 10.1038/nature14269 10.1164/rccm.201301-0059CI 10.1038/s41467-019-12582-y 10.1126/science.1063525 10.1093/hmg/dds408 10.1053/ajkd.2001.29216 10.1038/ng.263 10.1038/ng.3970 10.1016/j.ahj.2004.10.036 10.1016/j.jpeds.2008.05.059 10.1038/s41525-022-00311-2 10.1016/j.bbrc.2016.04.036 10.1038/78140 10.1038/npjschz.2016.12 |
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| References_xml | – volume: 20 start-page: 481 year: 2009 ident: B4 article-title: Polarized traffic of LRP1 involves AP1B and SNX17 operating on Y-dependent sorting motifs in different pathways publication-title: Mol. Biol. Cell doi: 10.1091/mbc.e08-08-0805 – volume: 39 start-page: 1890 year: 2002 ident: B20 article-title: The incidence of congenital heart disease publication-title: J. Am. Coll. Cardiol. doi: 10.1016/S0735-1097(02)01886-7 – volume: 49 start-page: 1152 year: 2017 ident: B33 article-title: The complex genetics of hypoplastic left heart syndrome publication-title: Nat. Genet. doi: 10.1038/ng.3870 – volume: 169 start-page: 1195 year: 2010 ident: B53 article-title: Prevalence of congenital heart defects and persistent pulmonary hypertension of the neonate with Down syndrome publication-title: Eur. J. Pediatr. doi: 10.1007/s00431-010-1200-0 – volume: 12 start-page: 847 year: 2022 ident: B37 article-title: CPLANE complex and ciliopathies publication-title: Biomolecules doi: 10.3390/biom12060847 – volume: 37 start-page: D767 year: 2009 ident: B26 article-title: Human protein reference database—2009 update publication-title: Nucleic Acids Res doi: 10.1093/nar/gkn892 – volume: 6 start-page: 77 year: 2020 ident: B51 article-title: Motile ciliopathies publication-title: Nat. Rev. Dis. Primers doi: 10.1038/s41572-020-0209-6 – volume: 10 start-page: 25629 year: 2020 ident: B23 article-title: Cilia interactome with predicted protein–protein interactions reveals connections to Alzheimer's disease, aging and other neuropsychiatric processes publication-title: Sci. Rep. – volume: 120 start-page: e2218819120 year: 2023 ident: B34 article-title: Unraveling the intricate cargo-BBSome coupling mechanism at the ciliary tip publication-title: PNAS doi: 10.1073/pnas.2218819120 – volume: 32 start-page: 492 year: 1998 ident: B14 article-title: Frequency of 22q11 deletions in patients with conotruncal defects publication-title: J. Am. Coll. Cardiol. doi: 10.1016/S0735-1097(98)00259-9 – volume: 45 start-page: 951 year: 2013 ident: B19 article-title: ANKS6 is a central component of a nephronophthisis module linking NEK8 to INVS and NPHP3 publication-title: Nat. Genet. doi: 10.1038/ng.2681 – volume: 12 start-page: 105 year: 2017 ident: B30 article-title: A population-based analysis of mortality in patients with Turner syndrome and hypoplastic left heart syndrome using the Texas Birth Defects Registry publication-title: Congenit. Heart Dis. doi: 10.1111/chd.12413 – volume: 525 start-page: 109 year: 2015 ident: B6 article-title: Mutations in DCHS1 cause mitral valve prolapse publication-title: Nature doi: 10.1038/nature14670 – volume: 20 start-page: 223 year: 2018 ident: B43 article-title: Interpreting the clinical significance of combined variants in multiple recessive disease genes: systematic investigation of Joubert syndrome yields little support for oligogenicity publication-title: Genet. Med. doi: 10.1038/gim.2017.94 – volume: 5 start-page: 14 year: 2016 ident: B13 article-title: The cilia-regulated proteasome and its role in the development of ciliopathies and cancer publication-title: Cilia doi: 10.1186/s13630-016-0035-3 – volume: 55 start-page: 605 year: 2012 ident: B22 article-title: Severe aortic stenosis, bicuspid aortic valve and atrial septal defect in a child with Joubert Syndrome and Related Disorders (JSRD)—a case report and review of congenital heart defects reported in the human ciliopathies publication-title: Eur. J. Med. Genet. doi: 10.1016/j.ejmg.2012.07.010 – volume: 52 start-page: 1145 year: 2020 ident: B29 article-title: Evidence for secondary-variant genetic burden and non-random distribution across biological modules in a recessive ciliopathy publication-title: Nat. Genet. doi: 10.1038/s41588-020-0707-1 – volume: 204 start-page: 31 year: 2019 ident: B40 article-title: Thoraco-abdominal abnormalities in Bardet-Biedl syndrome: situs inversus and heterotaxy publication-title: J. Pediatr. doi: 10.1016/j.jpeds.2018.08.068 – volume: 10 start-page: 108 year: 2014 ident: B28 article-title: Cilia and coordination of signaling networks during heart development publication-title: Organogenesis doi: 10.4161/org.27483 – volume: 6 start-page: 6023 year: 2015 ident: B2 article-title: ANKS6 is the critical activator of NEK8 kinase in embryonic situs determination and organ patterning publication-title: Nat. Commun. doi: 10.1038/ncomms7023 – volume: 3 start-page: 100501 year: 2022 ident: B47 article-title: Genetic resiliency associated with dominant lethal TPM1 mutation causing atrial septal defect with high heritability publication-title: Cell Rep. Med. doi: 10.1016/j.xcrm.2021.100501 – volume: 83 start-page: 559 year: 2008 ident: B15 article-title: CC2D2A is mutated in Joubert syndrome and interacts with the ciliopathy-associated basal body protein CEP290 publication-title: Am. J. Hum. Genet. doi: 10.1016/j.ajhg.2008.10.002 – volume: 74 start-page: 4077 year: 2017 ident: B1 article-title: Routes and machinery of primary cilium biogenesis publication-title: Cell. Mol. Life Sci. doi: 10.1007/s00018-017-2570-5 – volume: 19 start-page: 711 year: 2017 ident: B12 article-title: Ciliopathy variant burden and developmental delay in children with hypoplastic left heart syndrome publication-title: Genet. Med. doi: 10.1038/gim.2016.167 – volume: 18 start-page: 533 year: 2017 ident: B44 article-title: Genes and molecular pathways underpinning ciliopathies publication-title: Nat. Rev. Mol. Cell Biol. doi: 10.1038/nrm.2017.60 – volume: 140 start-page: 1331 year: 2019 ident: B8 article-title: Defects in the exocyst-cilia machinery cause bicuspid aortic valve disease and aortic stenosis publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.119.038376 – volume: 6 start-page: 175 year: 2018 ident: B9 article-title: Congenital heart defects and ciliopathies associated with renal phenotypes publication-title: Front. Pediatr. doi: 10.3389/fped.2018.00175 – volume: 47 start-page: D529 year: 2019 ident: B41 article-title: The BioGRID interaction database: 2019 update publication-title: Nucleic Acids Res doi: 10.1093/nar/gky1079 – volume: 14 start-page: 756 year: 1989 ident: B7 article-title: Congenital cardiovascular malformations: questions on inheritance publication-title: J. Am. Coll. Cardiol. doi: 10.1016/0735-1097(89)90122-8 – volume: 7 start-page: 31 year: 2014 ident: B32 article-title: Interrogating congenital heart defects with noninvasive fetal echocardiography in a mouse forward genetic screen publication-title: Circ. Cardiovasc. Imaging doi: 10.1161/CIRCIMAGING.113.000451 – volume: 383 start-page: 16 year: 2009 ident: B46 article-title: The polycystic kidney disease-related proteins Bicc1 and SamCystin interact publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2009.03.113 – volume: 11 start-page: eaax0290 year: 2019 ident: B48 article-title: Primary cilia defects causing mitral valve prolapse publication-title: Sci. Transl. Med. doi: 10.1126/scitranslmed.aax0290 – year: 2023 ident: B10 article-title: Pathogenic mechanisms underlying adverse neurodevelopmental outcome in congenital heart disease – volume: 48 start-page: 648 year: 2016 ident: B49 article-title: The ciliopathy-associated CPLANE proteins direct basal body recruitment of intraflagellar transport machinery publication-title: Nat. Genet. doi: 10.1038/ng.3558 – volume: 148 start-page: 575 year: 2023 ident: B5 article-title: Survival from birth until young adulthood among individuals with congenital heart defects: CH STRONG publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.123.064400 – volume: 47 start-page: 1260 year: 2015 ident: B16 article-title: MMP21 is mutated in human heterotaxy and is required for normal left-right asymmetry in vertebrates publication-title: Nat. Genet. doi: 10.1038/ng.3376 – volume: 126 start-page: 1143 year: 2012 ident: B36 article-title: Neurodevelopmental outcomes in children with congenital heart disease: evaluation and management: a scientific statement from the American Heart Association publication-title: Circulation doi: 10.1161/CIR.0b013e318265ee8a – volume: 13 start-page: 627 year: 2022 ident: B24 article-title: Novel protein–protein interactions highlighting the crosstalk between hypoplastic left heart syndrome, ciliopathies and neurodevelopmental delays publication-title: Genes doi: 10.3390/genes13040627 – volume: 122 start-page: 2264 year: 2010 ident: B38 article-title: Temporal trends in survival to adulthood among patients born with congenital heart disease from 1970 to 1992 in Belgium publication-title: Circulation doi: 10.1161/CIRCULATIONAHA.110.946343 – volume: 521 start-page: 520 year: 2015 ident: B31 article-title: Global genetic analysis in mice unveils central role for cilia in congenital heart disease publication-title: Nature doi: 10.1038/nature14269 – volume: 188 start-page: 913 year: 2013 ident: B27 article-title: Primary ciliary dyskinesia: recent advances in diagnostics, genetics, and characterization of clinical disease publication-title: Am. J. Respir. Crit. Care Med. doi: 10.1164/rccm.201301-0059CI – volume: 10 start-page: 4722 year: 2019 ident: B52 article-title: De novo and recessive forms of congenital heart disease have distinct genetic and phenotypic landscapes publication-title: Nat. Commun. doi: 10.1038/s41467-019-12582-y – volume: 293 start-page: 2256 year: 2001 ident: B25 article-title: Triallelic inheritance in Bardet-Biedl syndrome, a Mendelian recessive disorder publication-title: Science doi: 10.1126/science.1063525 – volume: 18 start-page: 25 year: 2016 ident: B18 article-title: Congenital heart disease and primary ciliary dyskinesia publication-title: Paediatr. Respir. Rev. – volume: 21 start-page: 5528 year: 2012 ident: B17 article-title: The ciliopathy disease protein NPHP9 promotes nuclear delivery and activation of the oncogenic transcriptional regulator TAZ publication-title: Hum. Mol. Genet. doi: 10.1093/hmg/dds408 – volume: 38 start-page: 1208 year: 2001 ident: B35 article-title: Mitral valve prolapse and mitral regurgitation are common in patients with polycystic kidney disease type 1 publication-title: Am. J. Kidney Dis. doi: 10.1053/ajkd.2001.29216 – volume: 40 start-page: 1445 year: 2008 ident: B54 article-title: Foxj1 transcription factors are master regulators of the motile ciliogenic program publication-title: Nat. Genet. doi: 10.1038/ng.263 – volume: 49 start-page: 1593 year: 2017 ident: B21 article-title: Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands publication-title: Nat. Genet. doi: 10.1038/ng.3970 – volume: 150 start-page: 513 year: 2005 ident: B50 article-title: The prevalence of bicuspid aortic valve in newborns by echocardiographic screening publication-title: Am. Heart J. doi: 10.1016/j.ahj.2004.10.036 – volume: 153 start-page: 807 year: 2008 ident: B45 article-title: Prevalence of congenital heart defects in metropolitan Atlanta, 1998–2005 publication-title: J. Pediatr. doi: 10.1016/j.jpeds.2008.05.059 – volume: 7 start-page: 41 year: 2022 ident: B42 article-title: Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome publication-title: npj Genom. Med. doi: 10.1038/s41525-022-00311-2 – volume: 473 start-page: 1177 year: 2016 ident: B3 article-title: The atypical cadherin Dachsous1 localizes to the base of the ciliary apparatus in airway epithelia publication-title: Biochem. Biophys. Res. Commun. doi: 10.1016/j.bbrc.2016.04.036 – volume: 25 start-page: 440 year: 2000 ident: B39 article-title: A systematic, genome-wide, phenotype-driven mutagenesis programme for gene function studies in the mouse publication-title: Nat. Genet. doi: 10.1038/78140 – volume: 2 start-page: 16012 year: 2016 ident: B11 article-title: Schizophrenia interactome with 504 novel protein–protein interactions publication-title: npj Schizophr. doi: 10.1038/npjschz.2016.12 |
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| SubjectTerms | Animals cilia Cilia - genetics Cilia - metabolism Cilia - pathology complex genetics congenital heart disease Heart Defects, Congenital - genetics Heart Defects, Congenital - pathology Humans Mice Mutation Protein Interaction Maps Signal Transduction |
| Title | The Role of Cilia and the Complex Genetics of Congenital Heart Disease |
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