Abstract
The task of identifying mutations in nucleic acid sequences is a vital component of research in mammalian genetics. With the advent of the polymerase chain reaction, several useful mutation detection techniques have evolved in recent years. The different methods have complementing strengths and a suitable procedure for virtually any experimental situation is now available.
This is a preview of subscription content, access via your institution
Relevant articles
Open Access articles citing this article.
-
The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers
British Journal of Cancer Open Access 02 August 2005
Access options
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Get just this article for as long as you need it
$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Chehab, F.F. & Wall, J. Detection of multiple cystic fibrosis mutations by reverse dot blot hybridization: a technology for carrier screening. Hum. Genet. 89, 163–168 (1992).
Ng, I.S. et al. Methods for analysis of multiple cystic fibrosis mutations. Hum. Genet. 87, 613–617 (1991).
Ballabio, A. et al. Molecular heterogeneity of steroid sulfatase deficiency: a multicenter study on 57 unrelated patients, at DNA and protein levels. Genomics 4, 36–40 (1989).
Tsui, L.C. The spectrum of cystic fibrosis mutations. Trends Genet. 8, 392–398 (1992).
Koenig, M., Monaco, A.P. & Kunkel, L.M. The complete sequence of dystrophin predicts a rod-shaped cytoskeletal protein. Cell 53, 219–226 (1988).
Sinclair, A.H. et al. A gene from the human sex-determining region encodes a protein with homology to a conserved DNA-binding motif. Nature 346, 240–244 (1990).
Rooney, D.E. & Czepulkowski, B.H. Human cytogenetics: a practical approach (IRL Press, Oxford, New York, 1992).
Zhang, F.R., Heilig, R., Thomas, G. & Aurias, A. A one-step efficient and specific non-radioactive non-fluorescent method for in situ hybridization of banded chromosomes. Chromosoma 99, 436–439 (1990).
Baurmann, H., Cherif, D. & Berger, R. Interphase cytogenetics by fluorescent in situ hybridization (FISH) for characterization of monosomy-7-associated myeloid disorders. Leukemia 7, 384–391 (1993).
Taylor, C. et al. Diagnosis of Ewing's sarcoma and peripheral neuroectodermal tumour based on the detection of t(11;22) using fluorescence in situ hybridization. Br. J. Cancer 67, 128–133 (1993).
Kuwano, A., Ledbetter, S.A., Dobyns, W.B., Emanuel, B.S. & Ledbetter, D.H. Detection of deletions and cryptic translocations in Miller-Dieker syndrome by In situ hybridization. Am. J. hum. Genet. 49, 707–714 (1991).
Lupski, J.R. et al. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 66, 219–232 (1991).
Southern, E.M. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. molec. Blol. 98, 503–517 (1975).
Cooper, D.N. & Youssoufian, H. The CpG dinucleotide and human genetic disease. Hum. Genet. 78, 151–155 (1988).
Mullis, K.B. & Faloona, F.A. Specific synthesis of DNA in vitro via a polymerase-catalyzed chain reaction. Meth. Enzymol. 155, 335–350 (1987).
Sanger, F., Nicklen, S. & Coulson, A.R. DNA sequencing with chain-terminating inhibitors. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).
Maxam, A.M. & Gilbert, W. A new method for sequencing DNA. Proc. natn. Acad. Sci. U.S.A. 74, 560–564 (1977).
Chamberlain, J.S., Gibbs, R.A., Ranier, J.E., Nguyen, P.N. & Caskey, C.T. Deletion screening of the Duchenne muscular dystrophy locus via multiplex DNA amplification. Nucleic Acids Res. 16, 11141–11156 (1988).
Niemann, S.S. et al. Molecular genetic analysis of 67 patients with Duchenne/Becker muscular dystrophy. Hum. Genet. 90, 65–70 (1992).
Gibbs, R.A., Nguyen, P.N., Edwards, A., Civitello, A.B. & Caskey, C.T. Multiplex DNA deletion detection and exon sequencing of the hypoxanthine phosphoribosyltransferase gene in Lesch-Nyhan families. Genomics 7, 235–244 (1990).
Ballabio, A., Ranier, J.E., Chamberlain, J.S., Zollo, M. & Caskey, C.T. Screening for steroid sulfatase (STS) gene deletions by multiplex DNA amplification. Hum. Genet. 84, 571–573 (1990).
Abbs, S. & Bobrow, M. Analysis of quantitative PCR for the diagnosis of deletion and duplication carriers in the dystrophin gene. J. med. Genet. 29, 191–196 (1992).
Orita, M., Iwahana, H., Kanazawa, H., Hayashi, K. & Sekiya, T. Detection of polymorphisms of human DNA by gel electrophoresis as single-strand conformation polymorphisms. Proc. natn. Acad. Sci. U.S.A. 86, 2766–2770 (1989).
Ainsworth, P.J., Surh, L.C. & Coulter, M.M.B. Diagnostic single strand conformational polymorphism, (SSCP): a simplified non-radioisotopic method as applied to a Tay-Sachs B1 variant. Nucl. Acids Res. 19, 405–406 (1991).
Yap, E.P. & McGee, J.O. Nonisotopic SSCP detection in PCR products by ethidium bromide staining. Trends Genet. 8, 49 (1992).
Michaud, J. et al. Strand-separating conformational polymorphism analysis: efficacy of detection of point mutations in the human ornithine delta-aminotransferase gene. Genomics 13, 389–394 (1992).
Sheffield, V.C., Beck, J.S. & Kwitek, A.E. Analysis of the efficiency of single base substitution detection by SSCP 1–149 (Cold Spring Harbor Laboratory, New York, 1992).
Iwahana, H., Yoshimoto, K. & Itakara, M. Detection of point mutations by SSCP of PCR-amplified DNA after endonuclease digestion. Biotechniques 12, 64 (1992).
Sarkar, G., Yoon, H.S. & Sommer, S.S. Screening for mutations by RNA single-strand conformation polymorphism (rSSCP): comparison with DNA-SSCP. Nucl. Acids Res. 20, 871–878 (1992).
Myers, R.M., Maniatis, T. & Lerman, L.S. Detection and localization of single base changes by denaturing gradient gel electrophoresis. Meth. Enzymol. 155, 501–527 (1987).
Sheffield, V.C., Cox, D.R., Lerman, L.S. & Myers, R.M. Attachment of a 40-base-pair G + C-rich sequence (GC-clamp) to genomic DNA fragments by the polymerase chain reaction results in improved detection of single-base changes. Proc. natn. Acad. Sci. U.S.A. 86, 232–236 (1989).
Lerman, L.S. & Silverstein, K. Computational simulation of DNA melting and its application to denaturing gel electrophoresis. Meth. Enzymol. 155, 482–501 (1987).
Myers, R.M., Fischer, S.G., Lerman, L.S. & Maniatis, T. Nearly all single base substitutions in DNA fragments joined to a GC-clamp can be detected by denaturing gradient gel electrophoresis. Nucl. Acids Res. 13, 3131–3145 (1985).
Pellegata, N.S. et al. Detection of K-ras mutations by denaturing gradient gel electrophoresis (DGGE): a study on pancreatic cancer. Anticancer Res. 12, 1731–1735 (1992).
Fodde, R. et al. Eight novel inactivating germ line mutations at the APC gene identified by denaturing gradient gel electrophoresis. Genomics 13, 1162–1168 (1992).
Rosatelli, M.C. et al. Molecular characterization of beta-thalassemia in the Sardinian population. Am. J. hum. Genet. 50, 422–426 (1992).
Tee, M.K., Moran, C. & Nicholas, F.W. Temperature gradient gel electrophoresis: detection of a single base substitution in the cattle beta-lactoglobulin gene. Anim. Genet. 23, 431–435 (1992).
Nagamine, C.M., Chan, K. & Lau, Y.F.C. A PCR artifact: Generation of heteroduplexes. Am. J. hum. Genet. 45, 337–339 (1989).
Perry, D.J. & Carrell, R.W. Hydrolink gels: A rapid and simple approach to the detection of DNA mutations in thromboembolic disease. J. clin. Pathol. 45, 158–160 (1992).
White, M.B., Carvalho, M., Derse, D., O'Brien, S.J. & Dean, M. Detecting single base substitutions as heteroduplex polymorphisms. Genomics 12, 301–306 (1992).
Tassabehi, M. et al. Waardenburg's syndrome patients have mutations in the human homologue of the pax-3 paired box gene. Nature 355, 635–636 (1992).
Keen, J., Lester, D., Ingleheam, C., Curtis, A. & Bhattacharya, S. Rapid detection of single base mismatches as heteroduplexes on HydroLink gels. Trends Genet. 7, 5 (1991).
Artlich, A., Horn, M., Lorenz, B., Bhattacharya, S. & Gal, S. Recurrent 3-bp deletion at codon 255/256 of the rhodopsin gene in a German pedigree with autosomal dominant retinitis pigmentosa. Am. J. hum. Genet. 50, 876–878 (1992).
Veres, G., Gibbs, R.A., Scherer, S.E. & Caskey, C.T. The molecular basis of the sparse fur mouse mutation. Science 237, 415–417 (1987).
Gibbs, R.A. & Caskey, C.T. Identification and localization of mutations at the Lesch-Nyhan locus by ribonuclease A cleavage. Science 236, 303–305 (1987).
Myers, R.M., Larin, Z. & Maniatis, T. Detection of single base substitutions by ribonuclease cleavage at mismatches in RNA:DNA duplexes. Science 230, 1242–1246 (1985).
Cotton, R.G., Rodrigues, N.R. & Campbell, R.D. Reactivity of cytosine and thymine in single-base-pair mismatches with hydroxylamine and osmium tetroxide and its application to the study of mutations. Proc. natn. Acad. Sci. U.S.A. 85, 4397–4401 (1988).
Forrest, S.M., Dahl, H.H., Howells, D.W., Dianzani, I. & Cotton, R.G. Mutation detection in phenylketonuria by using chemical cleavage of mismatch: importance of using probes from both normal and patient samples. Am. J. hum. Genet. 49, 175–183 (1991).
Zheng, H. et al. Fidelity of targeted recombination in human fibroblasts and murine embryonic stem cells. Proc. natn. Acad. Sci. U.S.A. 88, 8067–8071 (1991).
Saleeba, J.A., Ramus, S.J. & Cotton, R.G.H. Complete mutation detection using unlabeled chemical cleavage. Hum. Mut. 1, 63–69 (1992).
Kilimann, M.W., Pizzuti, A., Grompe, M. & Caskey, C.T. Point mutations and polymorphisms in the human dystrophin gene identified in genomic DNA sequences amplified by multiplex PCR. Hum. Genet. 89, 253–258 (1992).
Ganguly, A. & Prockop, D.J. Detection of single–base mutations by reaction of DNA heteroduplexes with a water–soluble carbodiimide followed by primer extension: application to products from the polymerase chain reaction. Nucl. Acids Res. 18, 3933–3939 (1990).
Gyllensten, U.B. & Erlich, H.A. Generation of single-stranded DNA by the polymerase chain reaction and its application to direct sequencing of the HLA-DQA locus. Proc. natn. Acad. Sci. U.S.A. 85, 7652–7656 (1988).
Syvanen, A.C., Aalto, S.K., Kontula, K. & Soderlund, H. Direct sequencing of affinity-captured amplified human DNA application to the detection of apolipoprotein E polymorphism. FEBS Lett. 258, 71–74 (1989).
Stoflet, E.S., Koeberl, D.D., Sarkar, G. & Sommer, S.S. Genomic amplification with transcript sequencing. Science 239, 491–494 (1988).
Ruano, G. & Kidd, K.K. Coupled amplification and sequencing of genomic DNA. Proc. natn. Acad. Sci. U.S.A. 88, 2815–2819 (1991).
Craxton, M. Linear amplification sequencing, a powerful method for sequencing DNA. Methods 3, (1991).
Rosenthal, A. & Charnock, J.D.S. New protocols for DNA sequencing with dye terminators. DNA Seq. 3, 61–64 (1992).
Sarkar, G., Yoon, H.S. & Sommer, S.S. Dideoxy fingerprinting (ddE): a rapid and efficient screen for the presence of mutations. Genomics 13, 441–443 (1992).
Hattori, M., Yoshioka, K. & Sakaki, Y. High–sensitive fluorescent DNA sequencing and its application for detection and mass-screening of point mutations. Electrophoresis 13, 560–565 (1992).
Lu, A.L. & Hsu, I.C. Detection of single DNA base mutations with mismatch repair enzymes. Genomics 14, 249–255 (1992).
Chelly, J., Concordet, J.P., Kaplan, J.C. & Kahn, A. Illegitimate transcription: transcription of any gene in any cell type. Proc. natn. Acad. Sci. U.S.A. 86, 2617–2621 (1989).
Chelly, J. et al. Illegitimate transcription. Application to the analysisof truncated transcripts of the dystrophin gene in nonmuscle cultured cells from Duchenne and Becker patients. J. clin. Invest. 88, 1161–1166 (1991).
Jackson, D.P., Hayden, J.D. & Quirke, P. in PCR: A practical approach. (eds. McPherson, M.J., Quirke, P. & Taylor, G.R.) 41–42 (IRL press, Oxford, 1991).
Lin, B., Cotton, R.G., Trent, D.W. & Wright, P.J. Geographical clusters of dengue virus type 2 isolates based on analysis of infected cell RNA by the chemical cleavage at mismatch method. J. virol. Methods. 40, 205–218 (1992).
Grompe, M., Versalovic, J., Koeuth, T. & Lupski, J.R. Mutations in the Escherichia coli dnaG gene suggest coupling between DNA replication and chromosome partitioning. J. Bacteriol. 173, 1268–1278 (1991).
Sheffield, V.C., Fishman, G.A., Beck, J.S., Kimura, A.E. & Stone, E.M. Identification of novel rhodopsin mutations associated with retinitis pigmentosa by GC-clamped denaturing gradient gel electrophoresis. Am. J. hum. Genet. 49, 699–706 (1991).
Rossiter, J.F.R., Grompe, M. & Caskey, C.T. in PCR: A practical approach. (eds. McPherson, M.J., Quirke, P. & Taylor, G.R.) 75–83 (IRL press, Oxford, 1991).
Bevan, I.S., Rapley, R. & Walker, M.R. Sequencing of PCR-amplified DNA. PCR Meth. Appl. 1, 222–228 (1992).
Grompe, M., Muzny, D.M. & Caskey, C.T. Scanning detection of mutations in human ornithine transcarbamoylase by chemical mismatch cleavage. Proc. natn. Acad. Sci. U.S.A. 86, 5888–5892 (1989).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Grompe, M. The rapid detection of unknown mutations in nucleic acids. Nat Genet 5, 111–117 (1993). https://doi.org/10.1038/ng1093-111
Issue Date:
DOI: https://doi.org/10.1038/ng1093-111
This article is cited by
-
The role of MLH1, MSH2 and MSH6 in the development of multiple colorectal cancers
British Journal of Cancer (2005)
-
Scanning of guanine–guanine mismatches in DNA by synthetic ligands using surface plasmon resonance
Nature Biotechnology (2001)
-
Detection of mutations by automated fluorescence/RNA-based dideoxy fingerprinting (ARddF)
Oncogene (1999)
-
DNA variation and the future of human genetics
Nature Biotechnology (1998)