Genomic analyses of glycine decarboxylase neurogenic mutations yield a large-scale prediction model for prenatal disease
Autoři:
Joseph Farris aff001; Md Suhail Alam aff001; Arpitha Mysore Rajashekara aff001; Kasturi Haldar aff001
Působiště autorů:
Boler-Parseghian Center for Rare and Neglected Disease, University of Notre Dame, Notre Dame, Indiana, United States of America
aff001; Department of Biological Sciences, University of Notre Dame, Notre Dame, Indiana, United State of America
aff002
Vyšlo v časopise:
Genomic analyses of glycine decarboxylase neurogenic mutations yield a large-scale prediction model for prenatal disease. PLoS Genet 17(2): e1009307. doi:10.1371/journal.pgen.1009307
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1009307
Souhrn
Hundreds of mutations in a single gene result in rare diseases, but why mutations induce severe or attenuated states remains poorly understood. Defect in glycine decarboxylase (GLDC) causes Non-ketotic Hyperglycinemia (NKH), a neurological disease associated with elevation of plasma glycine. We unified a human multiparametric NKH mutation scale that separates severe from attenuated neurological disease with new in silico tools for murine and human genome level-analyses, gathered in vivo evidence from mice engineered with top-ranking attenuated and a highly pathogenic mutation, and integrated the data in a model of pre- and post-natal disease outcomes, relevant for over a hundred major and minor neurogenic mutations. Our findings suggest that highly severe neurogenic mutations predict fatal, prenatal disease that can be remedied by metabolic supplementation of dams, without amelioration of persistent plasma glycine. The work also provides a systems approach to identify functional consequences of mutations across hundreds of genetic diseases. Our studies provide a new framework for a large scale understanding of mutation functions and the prediction that severity of a neurogenic mutation is a direct measure of pre-natal disease in neurometabolic NKH mouse models. This framework can be extended to analyses of hundreds of monogenetic rare disorders where the underlying genes are known but understanding of the vast majority of mutations and why and how they cause disease, has yet to be realized.
Klíčová slova:
Hydrocephalus – Animal models of disease – Glycine – Homozygosity – Mouse models – Mutation – Substitution mutation – Formates
Zdroje
1. Christensen CK, Walsh L. Movement Disorders and Neurometabolic Diseases. Semin Pediatr Neurol. 2018 Apr;25:82–91. doi: 10.1016/j.spen.2018.02.003 29735120
2. Tharp BR. Neonatal seizures and syndromes. Epilepsia. 2002;43(3):2–10. doi: 10.1046/j.1528-1157.43.s.3.11.x 12060001
3. Karimzadeh P. Approach to neurometabolic diseases from a pediatric neurological point of view. Iran J child Neurol. 2015;9(1):1–16. 25767534
4. Locasale JW. Serine, glycine and one-carbon units: cancer metabolism in full circle. Nat Rev. 2013;13:572–83. doi: 10.1038/nrc3557 23822983
5. Yuan Y, Sun L, Wang X, Chen J, Jia M, Zou Y, et al. Identification of a new GLDC gene alternative splicing variant and its protumorigenic roles in lung cancer. Futur Oncol. 2019;15(36):4127–39. doi: 10.2217/fon-2019-0403 31773974
6. Kang PJ, Zheng J, Lee G, Son D, Kim IY, Song G, et al. Glycine decarboxylase regulates the maintenance and induction of pluripotency via metabolic control. Metab Eng. 2019 May;53:35–47. doi: 10.1016/j.ymben.2019.02.003 30779965
7. Zhou J, Wang D, Wong BH, Li C, Poon VK, Wen L, et al. Identification and characterization of GLDC as host susceptibility gene to severe influenza. EMBO Mol Med. 2019 Jan;11(1). doi: 10.15252/emmm.201809528 30498026
8. Zhang WC, Ng SC, Yang H, Rai A, Umashankar S, Ma S, et al. Glycine decarboxylase activity drives non-small cell lung cancer tumor-initiating cells and tumorigenesis. Cell. 2012;148:259–72. doi: 10.1016/j.cell.2011.11.050 22225612
9. Kim D, Fiske BP, Birsoy K, Freinkman E, Kami K, Possemato RL, et al. SHMT2 drives glioma cell survival in ischaemia but imposes a dependence on glycine clearance. Nature. 2015;520:363–7. doi: 10.1038/nature14363 25855294
10. Ducker GS, Rabinowitz JD. One-Carbon Metabolism in Health and Disease. Vol. 25, Cell Metabolism. Cell Press; 2017. p. 27–42.
11. Coughlin CR, Swanson MA, Kronquist K, Acquaviva C, Hutchin T, Rodriguez-Pombo P, et al. The genetic basis of classic nonketotic hyperglycinemia due to mutations in GLDC and AMT. Genet Med. 2017;19:104–11. doi: 10.1038/gim.2016.74 27362913
12. Kure S, Takayanagi M, Narisawa K, Tada K, Leisti J. Identification of a common mutation in finnish patients with nonketotic hyperglycinemia. J Clin Invest. 1992;90(1):160–4. doi: 10.1172/JCI115831 1634607
13. Indiana Genetics Advisory Committee Meeting Minutes April 13, 2010. 2010.
14. Hennermann JB, Berger JM, Grieben U, Scharer GH, Van Hove JLK. Prediction of long-term outcome in glycine encephalopathy: A clinical survey. J Inherit Metab Dis. 2012;35:253–61. doi: 10.1007/s10545-011-9398-1 22002442
15. Swanson MA, Coughlin CR, Scharer GH, Szerlong HJ, Bjoraker KJ, Spector EB, et al. Biochemical and molecular predictors for prognosis in nonketotic hyperglycinemia. Ann Neurol. 2015;78(4):606–18. doi: 10.1002/ana.24485 26179960
16. Farris J, Calhoun B, Alam MS, Lee S, Haldar K. Large scale analyses of genotype-phenotype relationships of glycine decarboxylase mutations and neurological disease severity. Ofran Y, editor. PLOS Comput Biol. 2020 May;16(5):e1007871. doi: 10.1371/journal.pcbi.1007871 32421718
17. Bjoraker KJ, Swanson MA, Coughlin CR, Christodoulou J, Tan ES, Fergeson M, et al. Neurodevelopmental Outcome and Treatment Efficacy of Benzoate and Dextromethorphan in Siblings with Attenuated Nonketotic Hyperglycinemia. J Pediatr. 2016;170:234–9. doi: 10.1016/j.jpeds.2015.12.027 26749113
18. Ryan TM, Ciavatta DJ, Townes TM. Knockout-transgenic mouse model of sickle cell disease. Science. 1997 Oct;278(5339):873–6. doi: 10.1126/science.278.5339.873 9346487
19. Maue RA, Burgess RW, Wang B, Wooley CM, Seburn KL, Vanier MT, et al. A novel mouse model of Niemann-Pick type C disease carrying a D1005G-Npc1 mutation comparable to commonly observed human mutations. Hum Mol Genet. 2012 Feb;21(4):730–50. doi: 10.1093/hmg/ddr505 22048958
20. Alam MS, Getz M, Haldar K. Chronic administration of an HDAC inhibitor treats both neurological and systemic Niemann-Pick type C disease in a mouse model. Sci Transl Med. 2016 Feb;8(326):326ra23. doi: 10.1126/scitranslmed.aad9407 26888431
21. Hasse D, Andersson E, Carlsson G, Masloboy A, Hagemann M, Bauwe H, et al. Structure of the homodimeric glycine decarboxylase P-protein from synechocystis sp. PCC 6803 suggests a mechanism for redox regulation. J Biol Chem. 2013;288(49):35333–45. doi: 10.1074/jbc.M113.509976 24121504
22. Dajnowicz S, Johnston RC, Parks JM, Blakeley MP, Keen DA, Weiss KL, et al. Direct visualization of critical hydrogen atoms in a pyridoxal 5′-phosphate enzyme. Nat Commun. 2017 Dec;8(1).
23. Scheiner S, Kar T, Pattanayak J. Comparison of various types of hydrogen bonds involving aromatic amino acids. J Am Chem Soc. 2002 Nov;124(44):13257–64. doi: 10.1021/ja027200q 12405854
24. Gray VE, Hause RJ, Fowler DM. Analysis of large-scale mutagenesis data to assess the impact of single amino acid substitutions. Genetics. 2017 Sep;207(1):53–61. doi: 10.1534/genetics.117.300064 28751422
25. Pai YJ, Leung K-Y, Savery D, Hutchin T, Prunty H, Heales S, et al. Glycine decarboxylase deficiency causes neural tube defects and features of non-ketotic hyperglycinemia in mice. Nat Commun. 2015;6:e6388. doi: 10.1038/ncomms7388 25736695
26. Yis U, Kurul SH, Dirik E. Nonketotic Hyperglycinemia and Acquired Hydrocephalus. Pediatr Neurol. 2009 Feb;40(2):138–40. doi: 10.1016/j.pediatrneurol.2008.10.007 19135633
27. Bravo-Alonso I, Navarrete R, Arribas-Carreira L, Perona A, Abia D, Couce ML, et al. Nonketotic hyperglycinemia: Functional assessment of missense variants in GLDC to understand phenotypes of the disease. Hum Mutat. 2017 Jun 1;38(6):678–91. doi: 10.1002/humu.23208 28244183
28. Van Hove JLK, Kishnani PS, Demaerel P, Kahler SG, Miller C, Jaeken J, et al. Acute hydrocephalus in nonketotic hyperglycinemia. Neurology. 2000 Feb;54(3):754–6. doi: 10.1212/wnl.54.3.754 10680820
29. Guex N, Peitsch MC, Schwede T. Automated comparative protein structure modeling with SWISS-MODEL and Swiss-PdbViewer: A historical perspective. Electrophoresis. 2009 Jun;30(S1):S162–73. doi: 10.1002/elps.200900140 19517507
30. Bienert S, Waterhouse A, de Beer TAP, Tauriello G, Studer G, Bordoli L, et al. The SWISS-MODEL Repository—new features and functionality. Nucleic Acids Res. 2017 Jan 4;45(D1):D313–9. doi: 10.1093/nar/gkw1132 27899672
31. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, et al. SWISS-MODEL: homology modelling of protein structures and complexes. Nucleic Acids Res. 2018 Jul 2;46(W1):W296–303. doi: 10.1093/nar/gky427 29788355
32. Sievers F, Wilm A, Dineen D, Gibson TJ, Karplus K, Li W, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol. 2011;7.
33. Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, et al. UCSF Chimera—A visualization system for exploratory research and analysis. J Comput Chem. 2004 Oct;25(13):1605–12. doi: 10.1002/jcc.20084 15264254
34. Ashkenazy H, Abadi S, Martz E, Chay O, Mayrose I, Pupko T, et al. ConSurf 2016: an improved methodology to estimate and visualize evolutionary conservation in macromolecules. Nucleic Acids Res. 2016 Jul 8;44(W1):W344–50. doi: 10.1093/nar/gkw408 27166375
35. Chan PP, Lowe TM. GtRNAdb 2.0: An expanded database of transfer RNA genes identified in complete and draft genomes. Nucleic Acids Res. 2016;44(D1):D184–9. doi: 10.1093/nar/gkv1309 26673694
Článek vyšel v časopise
PLOS Genetics
2021 Číslo 2
- ASCO 2024: Elektronické cigarety – riziko pro mladou generaci a naděje pro dospělé kuřáky
- Při vzniku života zřejmě hrály klíčovou roli obří viry
- FDA varuje před selfmonitoringem cukru pomocí chytrých hodinek. Jak je to v Česku?
- Vitaminy v topických magistraliter přípravcích – co je důležité vědět pro praxi?
- Ibuprofen jako alternativa antibiotik při léčbě infekcí močových cest
Nejčtenější v tomto čísle
- Glucocerebrosidase reduces the spread of protein aggregation in a Drosophila melanogaster model of neurodegeneration by regulating proteins trafficked by extracellular vesicles
- ATF3 downmodulates its new targets IFI6 and IFI27 to suppress the growth and migration of tongue squamous cell carcinoma cells
- Transcriptome-wide transmission disequilibrium analysis identifies novel risk genes for autism spectrum disorder
- Four families of folate-independent methionine synthases