Abstract
Array comparative genomic hybridization (aCGH) is a powerful clinical diagnostic tool that can be used to evaluate copy number changes in the genome. Targeted aCGH provides a much higher resolution in targeted gene regions to detect copy number changes within single gene or single exon. A custom-designed oligonucleotide aCGH platform (MitoMet®) has been developed to provide tiled coverage of the entire 16.6-kb mitochondrial genome and high-density coverage of a set of nuclear genes associated with metabolic and mitochondrial related disorders, for quick evaluation of copy number changes in both genomes (1). The high-density probes in mitochondrial genome on the MitoMet® array allow estimation of mtDNA deletion breakpoints and deletion heteroplasmy (2). This technology is particularly useful as a complementary diagnostic test to detect large deletions in genes related to mitochondrial disorders.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Wong, L. J., Dimmock, D., Geraghty, M. T., Quan, R., Lichter-Konecki, U., Wang, J., Brundage, E. K., Scaglia, F., and Chinault, A. C. (2008) Utility of oligonucleotide array-based comparative genomic hybridization for detection of target gene deletions. Clin Chem 54, 1141–8.
Chinault, A. C., Shaw, C. A., Brundage, E. K., Tang, L. Y., and Wong, L. J. (2009) Application of dual-genome oligonucleotide array-based comparative genomic hybridization to the molecular diagnosis of mitochondrial DNA deletion and depletion syndromes. Genet Med 11, 518–26.
Mendell, J. R., Buzin, C. H., Feng, J., Yan, J., Serrano, C., Sangani, D. S., Wall, C., Prior, T. W., and Sommer, S. S. (2001) Diagnosis of Duchenne dystrophy by enhanced detection of small mutations. Neurology 57, 645–50.
Shchelochkov, O. A., Li, F. Y., Geraghty, M. T., Gallagher, R. C., Van Hove, J. L., Lichter-Konecki, U., Fernhoff, P. M., Copeland, S., Reimschisel, T., Cederbaum, S., Lee, B., Chinault, A. C., and Wong, L. J. (2009) High-frequency detection of deletions and variable rearrangements at the ornithine transcarbamylase (OTC) locus by oligonucleotide array CGH. Mol Genet Metab 96, 97–105.
Schouten, J. P., McElgunn, C. J., Waaijer, R., Zwijnenburg, D., Diepvens, F., and Pals, G. (2002) Relative quantification of 40 nucleic acid sequences by multiplex ligation-dependent probe amplification. Nucleic Acids Res 30, e57.
Monaco, A. P., Bertelson, C. J., Middlesworth, W., Colletti, C. A., Aldridge, J., Fischbeck, K. H., Bartlett, R., Pericak-Vance, M. A., Roses, A. D., and Kunkel, L. M. (1985) Detection of deletions spanning the Duchenne muscular dystrophy locus using a tightly linked DNA segment. Nature 316, 842–5.
Bendavid, C., Kleta, R., Long, R., Ouspenskaia, M., Muenke, M., Haddad, B. R., and Gahl, W. A. (2004) FISH diagnosis of the common 57-kb deletion in CTNS causing cystinosis. Hum Genet 115, 510–4.
Sieber, O. M., Lamlum, H., Crabtree, M. D., Rowan, A. J., Barclay, E., Lipton, L., Hodgson, S., Thomas, H. J., Neale, K., Phillips, R. K., Farrington, S. M., Dunlop, M. G., Mueller, H. J., Bisgaard, M. L., Bulow, S., Fidalgo, P., Albuquerque, C., Scarano, M. I., Bodmer, W., Tomlinson, I. P., and Heinimann, K. (2002) Whole-gene APC deletions cause classical familial adenomatous polyposis, but not attenuated polyposis or “multiple” colorectal adenomas. Proc Natl Acad Sci USA 99, 2954–8.
Schrijver, I., Rappahahn, K., Pique, L., Kharrazi, M., and Wong, L. J. (2008) Multiplex ligation-dependent probe amplification identification of whole exon and single nucleotide deletions in the CFTR gene of Hispanic individuals with cystic fibrosis. J Mol Diagn 10, 368–75.
Boone, P. M., Bacino, C. A., Shaw, C. A., Eng, P. A., Hixson, P. M., Pursley, A. N., Kang, S. H., Yang, Y., Wiszniewska, J., Nowakowska, B. A., del Gaudio, D., Xia, Z., Simpson-Patel, G., Immken, L. L., Gibson, J. B., Tsai, A. C., Bowers, J. A., Reimschisel, T. E., Schaaf, C. P., Potocki, L., Scaglia, F., Gambin, T., Sykulski, M., Bartnik, M., Derwinska, K., Wisniowiecka-Kowalnik, B., Lalani, S. R., Probst, F. J., Bi, W., Beaudet, A. L., Patel, A., Lupski, J. R., Cheung, S. W., and Stankiewicz, P. (2010) Detection of clinically relevant exonic copy-number changes by array CGH. Hum Mutat 31, 1326–42.
Ou, Z., Kang, S. H., Shaw, C. A., Carmack, C. E., White, L. D., Patel, A., Beaudet, A. L., Cheung, S. W., and Chinault, A. C. (2008) Bacterial artificial chromosome-emulation oligonucleotide arrays for targeted clinical array-comparative genomic hybridization analyses. Genet Med 10, 278–89.
Dhami, P., Coffey, A. J., Abbs, S., Vermeesch, J. R., Dumanski, J. P., Woodward, K. J., Andrews, R. M., Langford, C., and Vetrie, D. (2005) Exon array CGH: detection of copy-number changes at the resolution of individual exons in the human genome. Am J Hum Genet 76, 750–62.
Lu, X., Shaw, C. A., Patel, A., Li, J., Cooper, M. L., Wells, W. R., Sullivan, C. M., Sahoo, T., Yatsenko, S. A., Bacino, C. A., Stankiewicz, P., Ou, Z., Chinault, A. C., Beaudet, A. L., Lupski, J. R., Cheung, S. W., and Ward, P. A. (2007) Clinical implementation of chromosomal microarray analysis: summary of 2513 postnatal cases. PLoS One 2, e327.
Brunetti-Pierri, N., Paciorkowski, A. R., Ciccone, R., Mina, E. D., Bonaglia, M. C., Borgatti, R., Schaaf, C. P., Sutton, V. R., Xia, Z., Jelluma, N., Ruivenkamp, C., Bertrand, M., de Ravel, T. J., Jayakar, P., Belli, S., Rocchetti, K., Pantaleoni, C., D’Arrigo, S., Hughes, J., Cheung, S. W., Zuffardi, O., and Stankiewicz, P. (2010) Duplications of FOXG1 in 14q12 are associated with developmental epilepsy, mental retardation, and severe speech impairment. Eur J Hum Genet.
Compton, A. G., Troedson, C., Wilson, M., Procopis, P. G., Li, F. Y., Brundage, E. K., Yamazaki, T., Thorburn, D. R., and Wong, L. J. (2010) Application of oligonucleotide array CGH in the detection of a large intragenic deletion in POLG associated with Alpers Syndrome. Mitochondrion.
Lee, N. C., Dimmock, D., Hwu, W. L., Tang, L. Y., Huang, W. C., Chinault, A. C., and Wong, L. J. (2009) Simultaneous detection of mitochondrial DNA depletion and single-exon deletion in the deoxyguanosine gene using array-based comparative genomic hybridisation. Arch Dis Child 94, 55–8.
Zhang, S., Li, F. Y., Bass, H. N., Pursley, A., Schmitt, E. S., Brown, B. L., Brundage, E. K., Mardach, R., and Wong, L. J. (2010) Application of oligonucleotide array CGH to the simultaneous detection of a deletion in the nuclear TK2 gene and mtDNA depletion. Mol Genet Metab 99, 53–7.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2012 Springer Science+Business Media, LLC
About this protocol
Cite this protocol
Wang, J., Rakhade, M. (2012). Utility of Array CGH in Molecular Diagnosis of Mitochondrial Disorders. In: Wong, Ph.D., LJ. (eds) Mitochondrial Disorders. Methods in Molecular Biology, vol 837. Humana Press. https://doi.org/10.1007/978-1-61779-504-6_20
Download citation
DOI: https://doi.org/10.1007/978-1-61779-504-6_20
Published:
Publisher Name: Humana Press
Print ISBN: 978-1-61779-503-9
Online ISBN: 978-1-61779-504-6
eBook Packages: Springer Protocols