Experimental Assessment of Splicing Variants Using Expression Minigenes and Comparison with In Silico Predictions

Human Mutation

Volumn 35, Issue 10, 2014, Pages 1249-1259

  Sharma, Neeraj ^a   Sosnay, Patrick R ^a   Ramalho, Anabela S ^b   Douville, Christopher ^c   Franca, Arianna ^a   Gottschalk, Laura B ^a   Park, Jeenah ^a   Lee, Melissa ^a   Vecchio Pagan, Briana ^a   Raraigh, Karen S ^a   Amaral, Margarida D ^b   Karchin, Rachel ^a   Cutting, Garry R ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF LISBON   (Portugal)

^c Johns Hopkins University   (United States)

Author keywords

CFTR; Expression minigene; In silico tools; Splicing

Indexed keywords

CFTR PROTEIN, HUMAN; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; RNA ISOFORM; RNA SPLICING;

CELL LINE; COMPARATIVE STUDY; COMPUTER SIMULATION; CYSTIC FIBROSIS; GENETIC PROCEDURES; GENETICS; HUMAN; METABOLISM; MUTATION; RNA SPLICING;

CELL LINE; COMPUTER SIMULATION; CYSTIC FIBROSIS; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; GENETIC TECHNIQUES; HUMANS; MUTATION; RNA ISOFORMS; RNA SPLICE SITES; RNA SPLICING;

EID: 84908665879     PISSN: 10597794     EISSN: 10981004     Source Type: Journal    
DOI: 10.1002/humu.22624     Document Type: Article

References (59)

1. Acedo A, Sanz DJ, Duran M, Infante M, Perez-Cabornero L, Miner C, Velasco EA. 2012. Comprehensive splicing functional analysis of DNA variants of the BRCA2 gene by hybrid minigenes. Breast Cancer Res 14:R87.
2. Aissat A, de Becdelievre A, Golmard L, Vasseur C, Costa C, Chaoui A, Martin N, Costes B, Goossens M, Girodon E, Fanen P, Hinzpeter, A. 2013. Combined computational-experimental analyses of CFTR exon strength uncover predictability of exon-skipping level. Hum Mutat 34:873-881.
3. Baralle M, Skoko N, Knezevich A, de Conti L, Motti D, Bhuvanagiri M, Baralle D, Buratti E, Baralle FE. 2006. NF1 mRNA biogenesis: effect of the genomic milieu in splicing regulation of the NF1 exon 37 region. FEBS Lett 580:4449-4456.
4. Bonnet C, Krieger S, Vezain M, Rousselin A, Tournier I, Martins A, Berthet P, Chevrier A, Dugast C, Layet V, Rossi A, Lidereau R, et al. 2008. Screening BRCA1 and BRCA2 unclassified variants for splicing mutations using reverse transcription PCR on patient RNA and an ex vivo assay based on a splicing reporter minigene. J Med Genet 45:438-446.
5. Bruscia E, Sangiuolo F, Sinibaldi P, Goncz KK, Novelli G, Gruenert DC. 2002. Isolation of CF cell lines corrected at DeltaF508-CFTR locus by SFHR-mediated targeting. Gene Ther 9:683-685.
6. Burge C, Karlin S. 1997. Prediction of complete gene structures in human genomic DNA. J Mol Biol 268:78-94.
7. Burset M, Seledtsov IA, Solovyev VV. 2000. Analysis of canonical and non-canonical splice sites in mammalian genomes. Nucleic Acids Res 28:4364-4375.
8. Cartegni L, Chew SL, Krainer AR. 2002. Listening to silence and understanding nonsense: exonic mutations that affect splicing. Nat Rev Genet 3:285-298.
9. Castellani C, Southern KW, Brownlee K, Dankert RJ, Duff A, Farrell M, Mehta A, Munck A, Pollitt R, Sermet-Gaudelus I, Wilcken B, Ballmann M, et al. 2009. European best practice guidelines for cystic fibrosis neonatal screening. J Cyst Fibros 8:153-173.
10. Chang YF, Imam JS, Wilkinson MF. 2007. The nonsense-mediated decay RNA surveillance pathway. Annu Rev Biochem 76:51-74.
11. Cheng SH, Gregory RJ, Marshall J, Paul S, Souza DW, White GA, O'Riordan CR, Smith AE. 1990. Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis. Cell 63:827-834.
12. Cooper DN, Krawczak M, Polychronakos C, Tyler-Smith C, Kehrer-Sawatzki H. 2013. Where genotype is not predictive of phenotype: towards an understanding of the molecular basis of reduced penetrance in human inherited disease. Hum Genet 132:1077-1130.
13. Cooper TA. 2005. Use of minigene systems to dissect alternative splicing elements. Methods 37:331-340.
14. Desmet FO, Hamroun D, Lalande M, Collod-Beroud G, Claustres M, Beroud C. 2009. Human Splicing Finder: an online bioinformatics tool to predict splicing signals. Nucleic Acids Res 37:e67.
15. Desmet FO, Hamroun D, Collod-Beroud G, Claustres M, Beroud, C. 2010. Bioinformatics identification of splice site signals and prediction of mutation effects. In: Mohan RM, editor. Recent advances in nucleic acid research, Kerala, India: Global Research Network. p 1-14.
16. Dogan RI, Getoor L, Wilbur WJ, Mount SM. 2007. SplicePort-an interactive splice-site analysis tool. Nucleic Acids Res 35:W285-W291.
17. Dominski Z, Kole R. 1991. Selection of splice sites in pre-mRNAs with short internal exons. Mol Cell Biol 11:6075-6083.
18. Ehrhardt C, Collnot EM, Baldes C, Becker U, Laue M, Kim KJ, Lehr CM. 2006. Towards an in vitro model of cystic fibrosis small airway epithelium: characterisation of the human bronchial epithelial cell line CFBE41o-. Cell Tissue Res 323:405-415.
19. Eriksson M, Brown WT, Gordon LB, Glynn MW, Singer J, Scott L, Erdos MR, Robbins CM, Moses TY, Berglund P, Dutra A, Pak E, et al. 2003. Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome. Nature 423:293-298.
20. Fededa JP, Petrillo E, Gelfand MS, Neverov AD, Kadener S, Nogues G, Pelisch F, Baralle FE, Muro AF, Kornblihtt AR. 2005. A polar mechanism coordinates different regions of alternative splicing within a single gene. Mol Cell 19:393-404.
21. Frischmeyer PA, Dietz HC. 1999. Nonsense-mediated mRNA decay in health and disease. Hum Mol Genet 8:1893-1900.
22. Goina E, Fernandez-Alanis E, Pagani F. 2011. Approaches to study CFTR pre-mRNA splicing defects. Methods Mol Biol 741:155-169.
23. Hastings ML, Krainer AR. 2001. Pre-mRNA splicing in the new millennium. Curr Opin Cell Biol 13:302-309.
24. Hefferon TW, Groman JD, Yurk CE, Cutting GR. 2004. A variable dinucleotide repeat in the CFTR gene contributes to phenotype diversity by forming RNA secondary structures that alter splicing. Proc Natl Acad Sci USA 101:3504-3509.
25. Highsmith WE, Jr., Lauranell BH, Zhaoqing Z, Olsen JC, Strong TV, Smith T, Friedman KJ, Silverman LM, Boucher RC, Collins FS, Knowles MR. 1997. Identification of a splice site mutation (2789+5G>A) associated with small amounts of normal CFTR mRNA and mild cystic fibrosis. Hum Mutat 9:332-338.
26. Houdayer C, Caux-Moncoutier V, Krieger S, Barrois M, Bonnet F, Bourdon V, Bronner M, Buisson M, Coulet F, Gaildrat P, Lefol C, Leone M, et al. 2012. Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Hum Mutat 33:1228-1238.
27. Houdayer C, Dehainault C, Mattler C, Michaux D, Caux-Moncoutier V, Pages-Berhouet S, d'Enghien CD, Lauge A, Castera L, Gauthier-Villars M, Stoppa-Lyonnet D. 2008. Evaluation of in silico splice tools for decision-making in molecular diagnosis. Hum Mutat 29:975-982.
28. Hull J, Shackleton S, Harris A. 1993. Abnormal mRNA splicing resulting from three different mutations in the CFTR gene. Hum Mol Genet 2:689-692.
29. Iossifov I, Ronemus M, Levy D, Wang Z, Hakker I, Rosenbaum J, Yamrom B, Lee YH, Narzisi G, Leotta A, Kendall J, Grabowska E, et al. 2012. De novo gene disruptions in children on the autistic spectrum. Neuron 74:285-299.
30. Jacob HJ, Abrams K, Bick DP, Brodie K, Dimmock DP, Farrell M, Geurts J, Harris J, Helbling D, Joers BJ, Kliegman R, Kowalski G, et al. 2013. Genomics in clinical practice: lessons from the front lines. Sci Transl Med 5:194cm5.
31. Jian X, Boerwinkle E, Liu X. 2013. In silico tools for splicing defect prediction: a survey from the viewpoint of end users. Genet Med.
32. Jordan CT, Cao L, Roberson ED, Pierson KC, Yang CF, Joyce CE, Ryan C, Duan S, Helms CA, Liu Y, Chen Y, McBride AA, et al. 2012. PSORS2 is due to mutations in CARD14. Am J Hum Genet 90:784-795.
33. Korf I, Flicek P, Duan D, Brent MR. 2001. Integrating genomic homology into gene structure prediction. Bioinformatics 17(Suppl 1):S140-S148.
34. Krasnov KV, Tzetis M, Cheng J, Guggino WB, Cutting GR. 2008. Localization studies of rare missense mutations in cystic fibrosis transmembrane conductance regulator (CFTR) facilitate interpretation of genotype-phenotype relationships. Hum Mutat 29:1364-1372.
35. Krawczak M, Thomas NS, Hundrieser B, Mort M, Wittig M, Hampe J, Cooper DN. 2007. Single base-pair substitutions in exon-intron junctions of human genes: nature, distribution, and consequences for mRNA splicing. Hum Mutat 28:150-158.
36. MacArthur DG, Manolio TA, Dimmock DP, Rehm HL, Shendure J, Abecasis GR, Adams DR, Altman RB, Antonarakis SE, Ashley EA, Barrett JC, Biesecker LG, et al. 2014. Guidelines for investigating causality of sequence variants in human disease. Nature 508:469-476.
37. Marden JH. 2008. Quantitative and evolutionary biology of alternative splicing: how changing the mix of alternative transcripts affects phenotypic plasticity and reaction norms. Heredity (Edinb) 100:111-120.
38. Masvidal L, Igreja S, Ramos MD, Alvarez A, de Gracia J, Ramalho A, Amaral MD, Larriba S, Casals T. 2014. Assessing the residual CFTR gene expression in human nasal epithelium cells bearing CFTR splicing mutations causing cystic fibrosis. Eur J Hum Genet 22:784-791.
39. Mereau A, Anquetil V, Cibois M, Noiret M, Primot A, Vallee A, Paillard L. 2009. Analysis of splicing patterns by pyrosequencing. Nucleic Acids Res 37:e126.
40. Mucaki EJ, Shirley BC, Rogan PK. 2013. Prediction of mutant mRNA splice isoforms by information theory-based exon definition. Hum Mutat 34:557-565.
41. Pagani F, Buratti E, Stuani C, Romano M, Zuccato E, Niksic M, Giglio L, Faraguna D, Baralle FE. 2000. Splicing factors induce cystic fibrosis transmembrane regulator exon 9 skipping through a nonevolutionary conserved intronic element. J Biol Chem 275:21041-21047.
42. Petkovic V, Godi M, Lochmatter D, Eble A, Fluck CE, Robinson IC, Mullis PE. 2010. Growth hormone (GH)-releasing hormone increases the expression of the dominant-negative GH isoform in cases of isolated GH deficiency due to GH splice-site mutations. Endocrinology 151:2650-2658.
43. Raynal C, Baux D, Theze C, Bareil C, Taulan M, Roux AF, Claustres M, Tuffery-Giraud S, des Georges M. 2013. A classification model relative to splicing for variants of unknown clinical significance: application to the CFTR gene. Hum Mutat. 34:774-874.
44. Reese MG, Eeckman FH, Kulp D, Haussler D. 1997. Improved splice site detection in Genie. J Comput Biol 4:311-323.
45. Sanders SJ, Murtha MT, Gupta AR, Murdoch JD, Raubeson MJ, Willsey AJ, Ercan-Sencicek AG, DiLullo NM, Parikshak NN, Stein JL, Walker MF, Ober GT, et al. 2012. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature 485:237-241.
46. Sankaran VG, Ghazvinian R, Do R, Thiru P, Vergilio JA, Beggs AH, Sieff CA, Orkin SH, Nathan DG, Lander ES, Gazda HT. 2012. Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia. J Clin Invest 122:2439-2443.
47. Schwartz S, Hall E, Ast G. 2009. SROOGLE: webserver for integrative, user-friendly visualization of splicing signals. Nucleic Acids Res 37:W189-W192.
48. Scott A, Petrykowska HM, Hefferon T, Gotea V, Elnitski L. 2012. Functional analysis of synonymous substitutions predicted to affect splicing of the CFTR gene. J Cyst Fibros 11:511-517.
49. Shapiro MB, Senapathy P. 1987. RNA splice junctions of different classes of eukaryotes: sequence statistics and functional implications in gene expression. Nucleic Acids Res 15:7155-7174.
50. Silva AL, Ribeiro P, Inacio A, Liebhaber SA, Romao L. 2008. Proximity of the poly(A)-binding protein to a premature termination codon inhibits mammalian nonsense-mediated mRNA decay. RNA 14:563-576.
51. Singh RK, Cooper TA. 2012. Pre-mRNA splicing in disease and therapeutics. Trends Mol Med 18:472-482.
52. Sosnay PR, Siklosi KR, Van Goor F, Kaniecki K, Yu H, Sharma N, Ramalho AS, Amaral MD, Dorfman R, Zielenski J, Masica DL, Karchin R, et al. 2013. Defining the disease liability of variants in the cystic fibrosis transmembrane conductance regulator gene. Nat Genet 45:1160-1167.
53. Spurdle AB, Couch FJ, Hogervorst FB, Radice P, Sinilnikova OM. 2008. Prediction and assessment of splicing alterations: implications for clinical testing. Hum Mutat 29:1304-1313.
54. Sterner DA, Berget SM. 1993. In vivo recognition of a vertebrate mini-exon as an exon-intron-exon unit. Mol Cell Biol 13:2677-2687.
55. Xue Y, Chen Y, Ayub Q, Huang N, Ball EV, Mort M, Phillips AD, Shaw K, Stenson PD, Cooper DN, Tyler-Smith C. 2012. Deleterious- and disease-allele prevalence in healthy individuals: insights from current predictions, mutation databases, and population-scale resequencing. Am J Hum Genet 91:1022-1032.
56. Yang Y, Muzny DM, Reid JG, Bainbridge MN, Willis A, Ward PA, Braxton A, Beuten J, Xia F, Niu Z, Hardison M, Person R, et al. 2013. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 369:1502-1511.
57. Yeo G, Burge CB. 2004. Maximum entropy modeling of short sequence motifs with applications to RNA splicing signals. 11:377-394.
58. Yeo GW, Van Nostrand EL, Liang TY. 2007. Discovery and analysis of evolutionarily conserved intronic splicing regulatory elements. PLoS Genet 3:e85.
59. Zhang XH, Leslie CS, Chasin LA. 2005. Computational searches for splicing signals. Methods 37:292-305.