Tuesday, April 1, 2025
No menu items!
HomeNatureThe contribution of de novo coding mutations to meningomyelocele

The contribution of de novo coding mutations to meningomyelocele

  • Iskandar, B. J. & Finnell, R. H. Spina bifida. N. Engl. J. Med. 387, 444–450 (2022).

    PubMed 

    Google Scholar
     

  • Lee, S. & Gleeson, J. G. Closing in on mechanisms of open neural tube defects. Trends Neurosci. 43, 519–532 (2020).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council vitamin study. Lancet 338, 131–137 (1991).

  • Arnold, J. A. Myelocyste, transposition von gewebskeimen und sympodie. Beitr. Pathol. Anat. 16, 1–28 (1894).

    MATH 

    Google Scholar
     

  • Chiari, H. Uber veränderungen des kleinhirns infolge von hydrocephalie des grosshirns. Dtsch. Med. Wochenschr. 17, 1172–1175 (1891).


    Google Scholar
     

  • Wilde, J. J., Petersen, J. R. & Niswander, L. Genetic, epigenetic, and environmental contributions to neural tube closure. Annu. Rev. Genet. 48, 583–611 (2014).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Carter, C. O. & Evans, K. Spina bifida and anencephalus in greater London. J. Med. Genet. 10, 209–234 (1973).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Zhang, T. et al. Genetic variants in the folate pathway and the risk of neural tube defects: a meta-analysis of the published literature. PLoS ONE 8, e59570 (2013).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lei, Y. et al. Identification of novel CELSR1 mutations in spina bifida. PLoS ONE 9, e92207 (2014).

    ADS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kibar, Z. et al. Mutations in VANGL1 associated with neural-tube defects. N. Engl. J. Med. 356, 1432–1437 (2007).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Morrison, K. et al. Genetic mapping of the human homologue (T) of mouse T (Brachyury) and a search for allele association between human T and spina bifida. Hum. Mol. Genet. 5, 669–674 (1996).

    CAS 
    PubMed 

    Google Scholar
     

  • Jensen, L. E., Etheredge, A. J., Brown, K. S., Mitchell, L. E. & Whitehead, A. S. Maternal genotype for the monocyte chemoattractant protein 1 A(-2518)G promoter polymorphism is associated with the risk of spina bifida in offspring. Am. J. Med. Genet. A 140, 1114–1118 (2006).

    PubMed 

    Google Scholar
     

  • Iossifov, I. et al. The contribution of de novo coding mutations to autism spectrum disorder. Nature 515, 216–221 (2014).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zaidi, S. et al. De novo mutations in histone-modifying genes in congenital heart disease. Nature 498, 220–223 (2013).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Lemay, P. et al. Loss-of-function de novo mutations play an important role in severe human neural tube defects. J. Med. Genet. 52, 493–497 (2015).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Fischbach, G. D. & Lord, C. The Simons Simplex Collection: a resource for identification of autism genetic risk factors. Neuron 68, 192–195 (2010).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Rahbari, R. et al. Timing, rates and spectra of human germline mutation. Nat. Genet. 48, 126–133 (2016).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Kessler, M. D. et al. De novo mutations across 1,465 diverse genomes reveal mutational insights and reductions in the Amish founder population. Proc. Natl Acad. Sci. USA 117, 2560–2569 (2020).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Besenbacher, S. et al. Novel variation and de novo mutation rates in population-wide de novo assembled Danish trios. Nat. Commun. 6, 5969 (2015).

    ADS 
    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Frome, E. L. The analysis of rates using Poisson regression models. Biometrics 39, 665–674 (1983).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Willsey, A. J. et al. De novo coding variants are strongly associated with Tourette disorder. Neuron 94, 486–499 (2017).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Dong, C. et al. Comparison and integration of deleteriousness prediction methods for nonsynonymous SNVs in whole exome sequencing studies. Hum. Mol. Genet. 24, 2125–2137 (2015).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Kong, A. et al. Rate of de novo mutations and the importance of father’s age to disease risk. Nature 488, 471–475 (2012).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Goldmann, J. M., Veltman, J. A. & Gilissen, C. De novo mutations reflect development and aging of the human germline. Trends Genet. 35, 828–839 (2019).

    CAS 
    PubMed 

    Google Scholar
     

  • Turner, T. N. et al. Genomic patterns of de novo mutation in simplex autism. Cell 171, 710–722 (2017).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Martin, J. et al. A brief report: de novo copy number variants in children with attention deficit hyperactivity disorder. Transl. Psychiatry 10, 135 (2020).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Sanders, S. J. et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 70, 863–885 (2011).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Hol, F. A. et al. A frameshift mutation in the gene for PAX3 in a girl with spina bifida and mild signs of Waardenburg syndrome. J. Med. Genet. 32, 52–56 (1995).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Szklarczyk, D. et al. The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Res. 51, D638–D646 (2023).

    CAS 
    PubMed 

    Google Scholar
     

  • Cowen, L., Ideker, T., Raphael, B. J. & Sharan, R. Network propagation: a universal amplifier of genetic associations. Nat. Rev. Genet. 18, 551–562 (2017).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Harris, M. J. & Juriloff, D. M. An update to the list of mouse mutants with neural tube closure defects and advances toward a complete genetic perspective of neural tube closure. Birth Defects Res. A Clin. Mol. Teratol. 88, 653–669 (2010).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Traag, V. A., Waltman, L. & van Eck, N. J. From Louvain to Leiden: guaranteeing well-connected communities. Sci. Rep. 9, 5233 (2019).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Rolo, A., Escuin, S., Greene, N. D. E. & Copp, A. J. Rho GTPases in mammalian spinal neural tube closure. Small GTPases 9, 283–289 (2018).

    CAS 
    PubMed 

    Google Scholar
     

  • Wallingford, J. B., Niswander, L. A., Shaw, G. M. & Finnell, R. H. The continuing challenge of understanding, preventing, and treating neural tube defects. Science 339, 1222002 (2013).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Niederkofler, V., Salie, R., Sigrist, M. & Arber, S. Repulsive guidance molecule (RGM) gene function is required for neural tube closure but not retinal topography in the mouse visual system. J. Neurosci. 24, 808–818 (2004).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kee, N., Wilson, N., Key, B. & Cooper, H. M. Netrin-1 is required for efficient neural tube closure. Dev. Neurobiol. 73, 176–187 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Greene, N. D., Stanier, P. & Moore, G. E. The emerging role of epigenetic mechanisms in the etiology of neural tube defects. Epigenetics 6, 875–883 (2011).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Akimova, D. et al. Metabolite profiling of whole murine embryos reveals metabolic perturbations associated with maternal valproate-induced neural tube closure defects. Birth Defects Res. 109, 106–119 (2017).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Copp, A. J., Stanier, P. & Greene, N. D. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol. 12, 799–810 (2013).

    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Schaar, B. T. & McConnell, S. K. Cytoskeletal coordination during neuronal migration. Proc. Natl Acad. Sci. USA 102, 13652–13657 (2005).

    ADS 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dent, E. W., Gupton, S. L. & Gertler, F. B. The growth cone cytoskeleton in axon outgrowth and guidance. Cold Spring Harb. Perspect. Biol. 3, a001800 (2011).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Geelen, J. A. & Langman, J. Closure of the neural tube in the cephalic region of the mouse embryo. Anat. Rec. 189, 625–640 (1977).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Rolo, A. et al. Regulation of cell protrusions by small GTPases during fusion of the neural folds. eLife 5, e13273 (2016).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hamosh, A., Scott, A. F., Amberger, J. S., Bocchini, C. A. & McKusick, V. A. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Res. 33, D514–D517 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Jin, S. C. et al. Contribution of rare inherited and de novo variants in 2,871 congenital heart disease probands. Nat. Genet. 49, 1593–1601 (2017).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Halvorsen, M. et al. De novo mutations in childhood cases of sudden unexplained death that disrupt intracellular Ca2+ regulation. Proc. Natl Acad. Sci. USA 118, e2115140118 (2021).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Li, W. et al. De novo mutations contributes approximately 7% of pathogenicity in inherited eye diseases. Invest. Ophthalmol. Vis. Sci. 64, 5 (2023).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Boyle, E. A., Li, Y. I. & Pritchard, J. K. An expanded view of complex traits: from polygenic to omnigenic. Cell 169, 1177–1186 (2017).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Lemos, M. C. et al. Genetic background influences embryonic lethality and the occurrence of neural tube defects in Men1 null mice: relevance to genetic modifiers. J. Endocrinol. 203, 133–142 (2009).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Momb, J. et al. Deletion of Mthfd1l causes embryonic lethality and neural tube and craniofacial defects in mice. Proc. Natl Acad. Sci. USA 110, 549–554 (2013).

    ADS 
    CAS 
    PubMed 

    Google Scholar
     

  • Chen, Z. et al. Threshold for neural tube defect risk by accumulated singleton loss-of-function variants. Cell Res. 28, 1039–1041 (2018).

    ADS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Bassuk, A. G. et al. Copy number variation analysis implicates the cell polarity gene glypican 5 as a human spina bifida candidate gene. Hum. Mol. Genet. 22, 1097–1111 (2013).

    CAS 
    PubMed 

    Google Scholar
     

  • Rendeli, C. et al. Assessment of health status in children with spina bifida. Spinal Cord 43, 230–235 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Dimitromanolakis, A., Paterson, A. D. & Sun, L. Fast and accurate shared segment detection and relatedness estimation in un-phased genetic data via TRUFFLE. Am. J. Hum. Genet. 105, 78–88 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lee, J. et al. Mutalisk: a web-based somatic MUTation AnaLyIS toolKit for genomic, transcriptional and epigenomic signatures. Nucleic Acids Res. 46, W102–W108 (2018).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Quinlan, A. R. & Hall, I. M. BEDTools: a flexible suite of utilities for comparing genomic features. Bioinformatics 26, 841–842 (2010).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Ioannidis, N. M. et al. REVEL: An ensemble method for predicting the pathogenicity of rare missense variants. Am. J. Hum. Genet. 99, 877–885 (2016).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Jaganathan, K. et al. Predicting splicing from primary sequence with deep learning. Cell 176, 535–548 (2019).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Giacopuzzi, E., Popitsch, N. & Taylor, J. C. GREEN-DB: a framework for the annotation and prioritization of non-coding regulatory variants from whole-genome sequencing data. Nucleic Acids Res. 50, 2522–2535 (2022).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Suvakov, M., Panda, A., Diesh, C., Holmes, I. & Abyzov, A. CNVpytor: a tool for copy number variation detection and analysis from read depth and allele imbalance in whole-genome sequencing. Gigascience 10, giab074 (2021).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, X. et al. Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications. Bioinformatics 32, 1220–1222 (2016).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Rausch, T. et al. DELLY: structural variant discovery by integrated paired-end and split-read analysis. Bioinformatics 28, i333–i339 (2012).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Chen, K. H., Boettiger, A. N., Moffitt, J. R., Wang, S. & Zhuang, X. RNA imaging. Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090 (2015).

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Delile, J. et al. Single cell transcriptomics reveals spatial and temporal dynamics of gene expression in the developing mouse spinal cord. Development 146, dev173807 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Soldatov, R. et al. Spatiotemporal structure of cell fate decisions in murine neural crest. Science 364, eaas9536 (2019).

    CAS 
    PubMed 
    MATH 

    Google Scholar
     

  • Simões-Costa, M. & Bronner, M. E. Establishing neural crest identity: a gene regulatory recipe. Development 142, 242–257 (2015).

    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Wolf, F. A., Angerer, P. & Theis, F. J. SCANPY: large-scale single-cell gene expression data analysis. Genome Biol. 19, 15 (2018).

    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Komatsu, N. et al. Development of an optimized backbone of FRET biosensors for kinases and GTPases. Mol. Biol. Cell 22, 4647–4656 (2011).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Rosenthal, S. B. et al. Mapping the common gene networks that underlie related diseases. Nat. Protoc. 18, 1745–1759 (2023).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Huang, J. K. et al. Systematic evaluation of molecular networks for discovery of disease genes. Cell Syst. 6, 484–495 (2018).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Duman, R. S., Sanacora, G. & Krystal, J. H. Altered connectivity in depression: GABA and glutamate neurotransmitter deficits and reversal by novel treatments. Neuron 102, 75–90 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tolias, K. F. et al. The Rac1-GEF Tiam1 couples the NMDA receptor to the activity-dependent development of dendritic arbors and spines. Neuron 45, 525–538 (2005).

    CAS 
    PubMed 

    Google Scholar
     

  • Duman, J. G. et al. The adhesion-GPCR BAI1 shapes dendritic arbors via Bcr-mediated RhoA activation causing late growth arrest. eLife 8, e47566 (2019).

    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Henrie, H. et al. Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue. J. Cell Biol. 219, e201909093 (2020).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).

    ADS 
    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Adasme, M. F. et al. PLIP 2021: expanding the scope of the protein–ligand interaction profiler to DNA and RNA. Nucleic Acids Res. 49, W530–W534 (2021).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Santos-Martins, D. et al. Accelerating AutoDock4 with GPUs and gradient-based local search. J. Chem. Theory Comput. 17, 1060–1073 (2021).

    CAS 
    PubMed 
    PubMed Central 
    MATH 

    Google Scholar
     

  • Sive, H., Grainger, R. M. & Harland, R. M. Early Development of Xenopus laevis: A Laboratory Manual (Cold Spring Harbor Laboratory Press, 2000).

  • RELATED ARTICLES

    Most Popular

    Recent Comments