Abstract
Microarrays containing oligonucleotide mutation probes are emerging as useful platforms for the diagnosis of genetic disease. Herein, we describe the development and validation of an inhouse microarray suitable for the diagnosis of common cystic fibrosis (CF) mutations in low-template DNA samples such as those taken for preimplantation genetic diagnosis and prenatal diagnosis. The success of the CF microarray was based on the ability to generate sufficient target DNA for hybridization to the array probes using either direct polymerase chain reaction (PCR) amplification or whole-genome amplification followed by PCR. From replicate experiments using target DNA carrying known CF mutations, it was possible to define strict diagnostic parameters for the accurate diagnosis of CF. This protocol serves as a general guide for DNA-testing laboratories to develop other microarray platforms that may eventually replace traditional PCR-based genetic testing in the near future.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Lander, E. S., Linton, L. M., Birren, B., et al. (2001) Initial sequencing and analysis of the human genome. Nature 409, 860–921.
Wells, D. and Sherlock, J. K. (1998) Strategies for preimplantation genetic diagnosis of single gene disorders by DNA amplification. Prenat. Diagn. 18, 1389–1401.
Handyside, A. H. and Delhanty, J. D. (1997) Preimplantation genetic diagnosis: strategies and surprises. Trends Genet. 13, 270–275.
Cronin, M. T., Fucini, R. V., Kim, S. M., Masino, R. S., Wespi, R. M., and Miyada, C. G. (1996) Cystic fibrosis mutation detection by hybridization to light-generated DNA probe arrays. Hum. Mutat. 7, 244–255.
Southern, E. M. (1996) DNA chips: analysing sequence by hybridization to oligonucleotides on a large scale. Trends Genet. 12, 110–115.
Gilbert, F. (2001) Cystic fibrosis carrier screening: steps in the development of a mutation panel. Genet. Test 5, 223–227.
Kawasaki, E. S. (2004) Microarrays and the gene expression profile of a single cell. Ann. NY Acad. Sci. 1020, 92–100.
Ginsberg, S. D., Elarova, I., Ruben, M., et al. (2004) Single-cell gene expression analysis: implications for neurodegenerative and neuropsychiatric disorders. Neurochem. Res. 29, 1053–1064.
Fiegler, H., Carr, P., Douglas, E. J., et al. (2003) DNA microarrays for comparative genomic hybridization based on DOP-PCR amplification of BAC and PAC clones. Genes Chromosomes Cancer 36, 361–374.
Hu, D. G., Webb, G., and Hussey, N. (2004) Aneuploidy detection in single cells using DNA array-based comparative genomic hybridization. Mol. Hum. Reprod. 10, 283–289.
Kim, I. J., Kang, H. C., Park, J. H., et al. (2003) Development and applications of a beta-catenin oligonucleotide microarray: beta-catenin mutations are dominantly found in the proximal colon cancers with microsatellite instability. Clin. Cancer Res. 9, 2920–2925.
Fang, N. Y., Greiner, T. C., Weisenburger, D. D., et al. (2003) Oligonucleotide microarrays demonstrate the highest frequency of ATM mutations in the mantle cell subtype of lymphoma. Proc. Natl. Acad Sci. USA 100, 5372–5377.
Dumur, C. I., Dechsukhum, C., Ware, J. L., et al. (2003) Genome-wide detection of LOH in prostate cancer using human SNP microarray technology. Genomics 81, 260–269.
Tillib, S. V. and Mirzabekov, A. D. (2001) Advances in the analysis of DNA sequence variations using oligonucleotide microchip technology. Curr. Opin. Biotechnol. 12, 53–58.
Bains, W (1994) Selection of oligonucleotide probes and experimental conditions for multiplex hybridization experiments. Genet. Anal. Tech. Appl. 11, 49–62.
Bednar, M. (2000) DNA microarray technology and application. Med. Sci. Monit. 6, 796–800.
Hacia, J. G. and Collins, F. S. (1999) Mutational analysis using oligonucleotide microarrays. J. Med. Genet. 36, 730–736.
Kozal, M. J., Shah, N., Shen, N., et al. (1996) Extensive polymorphisms observed in HIV-1 clade B protease gene using high-density oligonucleotide arrays. Nat. Med. 2, 753–759.
Sapolsky, R. J., Hsie, L., Berno, A., Ghandour, G., Mittmann, M., and Fan, J. B. (1999) High-throughput polymorphism screening and genotyping with high-density oligonucleotide arrays. Genet. Anal. 14, 187–192.
Lipshutz, R. J., Fodor, S. P., Gingeras, T. R., and Lockhart, D. J. (1999) High density synthetic oligonucleotide arrays. Nat. Genet. 21, 20–24.
Mei, R., Galipeau, P. C., Prass, C., et al. (2000) Genome-wide detection of allelic imbalance using human SNPs and high-density DNA arrays. Genome Res. 10, 1126–1137.
Stears, R. L., Martinsky, T., and Schena, M. (2003) Trends in microarray analysis. Nat. Med. 9, 140–145.
Yershov, G., Barsky, V., Belgovskiy, A., et al. (1996) DNA analysis and diagnostics on oligonucleotide microchips. Proc. Natl. Acad. Sci. USA 93, 4913–4918.
Hacia, J. G., Brody, L. C., Chee, M. S., Fodor, S. P., and Collins, F. S. (1996) Detection of heterozygous mutations in BRCA1 using high density oligonucleotide arrays and two-colour fluorescence analysis. Nat. Genet. 14, 441–447.
Hacia, J. G., Woski, S.A., Fidanza, J., et al. (1998) Enhanced high density oligonucleotide array-based sequence analysis using modified nucleoside triphosphates. Nucleic Acids Res. 26, 4975–4982.
Hacia, J. G., Edgemon, K., Fang, N., et al. (2000) Oligonucleotide microarray based detection of repetitive sequence changes. Hum. Mutat. 16, 354–363.
Favis, R., Day, J. P., Gerry, N. P., Phelan, C., Narod, S., and Barany, F. (2000) Universal DNA array detection of small insertions and deletions in BRCA1 and BRCA2. Nat. Biotechnol. 18, 561–564.
Kim, I. J., Kang, H. C., Park, J. H., et al. (2002) RET oligonucleotide microarray for the detection of RET mutations in multiple endocrine neoplasia type 2 syndromes. Clin. Cancer Res. 8, 457–463.
Hacia, J. G., Sun, B., Hunt, N., et al. (1998) Strategies for mutational analysis of the large multiexon ATM gene using high-density oligonucleotide arrays. Genome Res. 8, 1245–1258.
Primdahl, H., Wikman, F. P., von der Maase, H., Zhou, X. G., Wolf, H., and Orntoft, T. F. (2002) Allelic imbalances in human bladder cancer: genome-wide detection with high-density single-nucleotide polymorphism arrays. J. Natl. Cancer Inst. 94, 216–223.
Hoque, M. O., Lee, C. C., Cairns, P., Schoenberg, M., and Sidransky, D. (2003) Genome-wide genetic characterization of bladder cancer: a comparison of high-density single-nucleotide polymorphism arrays and PCR-based microsatellite analysis. Cancer Res. 63, 2216–2222.
Blohm, D. H. and Guiseppi-Elie, A. (2001) New developments in microarray technology. Curr. Opin. Biotechnol. 12, 41–47.
Findlay, I., Matthews, P., and Quirke, P. (1998) Multiple genetic diagnoses from single cells using multiplex PCR: reliability and allele dropout. Prenat. Diagn. 18, 1413–1421.
Wells, D., Sherlock, J. K., Handyside, A. H., and Delhanty, J. D. (1999) Detailed chromosomal and molecular genetic analysis of single cells by whole genome amplification and comparative genomic hybridisation. Nucleic Acids Res. 27, 1214–1218.
Katz, M. G., Trounson, A. O., and Cram, D. S. (2002) DNA fingerprinting of sister blastomeres from human IVF embryos. Hum. Reprod. 17, 752–759.
Piyamongkol, W., Bermudez, M. G., Harper, J. C., and Wells, D. (2003) Detailed investigation of factors influencing amplification efficiency and allele drop-out in single cell PCR: implications for preimplantation genetic diagnosis. Mol. Hum. Reprod. 9, 411–420.
Harper, J. C. and Wells, D. (1999) Recent advances and future developments in PGD. Prenat. Diagn. 19, 1193–1199.
Zhang, L., Cui, X., Schmitt, K., Hubert, R., Navidi, W., and Arnheim, N. (1992) Whole genome amplification from a single cell: implications for genetic analysis. Proc. Natl. Acad. Sci. USA 89, 5847–5851.
Sermon, K., Lissens, W., Joris, H., Van Steirteghem, A., and Liebaers, I. (1996) Adaptation of the primer extension preamplification (PEP) reaction for preimplantation diagnosis: single blastomere analysis using short PEP protocols. Mol. Hum. Reprod. 2, 209–212.
Dietmaier, W., Hartmann, A., Wallinger, S., et al. (1999) Multiple mutation analyses in single tumor cells with improved whole genome amplification. Am. J. Pathol. 154, 83–95.
Cheung, V. G. and Nelson, S. F. (1996) Whole genome amplification using a degenerate oligonucleotide primer allows hundreds of genotypes to be performed on less than one nanogram of genomic DNA. Proc. Natl. Acad. Sci. USA 93, 14,676–14,679.
Dean, F. B., Hosono, S., Fang, L., et al. (2002) Comprehensive human genome amplification using multiple displacement amplification. Proc. Natl. Acad. Sci. USA 99, 5261–5266.
Salvado, C. S., Trounson, A. O., and Cram, D. S. (2004) Towards preimplantation diagnosis of cystic fibrosis using microarrays. Reprod. Biomed. Online 8, 107–114.
Urakawa, H., El Fantroussi, S., Smidt, H., et al. (2003) Optimization of single-base-pair mismatch discrimination in oligonucleotide microarrays. Appl. Environ. Microbiol. 69, 2848–2856.
Anthony, R. M., Schuitema, A. R., Chan, A. B., Boender, P. J., Klatser, P. R., and Oskam, L. (2003) Effect of secondary structure on single nucleotide polymorphism detection with a porous microarray matrix: implications for probe selection. Biotechniques 34, 1082–1086, 1088, 1089.
Solinas-Toldo, S., Lampel, S., Stilgenbauer, S., et al. (1997) Matrix-based comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20, 399–407.
Wong, K. K., Tsang, Y. T., Shen, J., et al. (2004) Allelic imbalance analysis by high-density single-nucleotide polymorphic allele (SNP) array with whole genome amplified DNA. Nucleic Acids Res. 32, e69.
Dreesen, J. C., Jacobs, L. J., Bras, M., et al. (2000) Multiplex PCR of polymorphic markers flanking the CFTR gene: a general approach for preimplantation genetic diagnosis of cystic fibrosis. Mol. Hum. Reprod. 6, 391–396.
Moutou, C., Gardes, N., and Viville, S. (2002) Multiplex PCR combining deltaF508 mutation and intragenic microsatellites of the CFTR gene for pre-implantation genetic diagnosis (PGD) of cystic fibrosis. Eur. J. Hum. Genet. 10, 231–238.
Vrettou, C., Tzetis, M., Traeger-Synodinos, J., Palmer, G., and Kanavakis, E. (2002) Multiplex sequence variation detection throughout the CFTR gene appropriate for preimplantation genetic diagnosis in populations with heterogeneity of cystic fibrosis mutations. Mol. Hum. Reprod. 8, 880–886.
Abou-Sleiman, P. M., Apessos, A., Harper, J. C., Serhal, P., Winston, R. M., and Delhanty, J. D. (2002) First application of preimplantation genetic diagnosis to neurofibromatosis type 2 (NF2). Prenat. Diagn. 22, 519–524.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2007 Humana Press Inc., Totowa, NJ
About this protocol
Cite this protocol
Salvado, C., Cram, D. (2007). Microarray Technology for Mutation Analysis of Low-Template DNA Samples. In: Thornhill, A. (eds) Single Cell Diagnostics. Methods in Molecular Medicine™, vol 132. Humana Press. https://doi.org/10.1007/978-1-59745-298-4_13
Download citation
DOI: https://doi.org/10.1007/978-1-59745-298-4_13
Publisher Name: Humana Press
Print ISBN: 978-1-58829-578-1
Online ISBN: 978-1-59745-298-4
eBook Packages: Springer Protocols