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Multicolor chromosome painting in diagnostic and research applications

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Abstract

For many years whole chromosome painting probes have been the work-horses in a large variety of clinical and research molecular cytogenetic applications. In recent years painting probes have been complemented by an increasing number of further region-specific probes, which allow the specific staining of centromeres, subtelomeres or other regions within the genome. This development of new probe sets was greatly facilitated by the Human Genome Project from which well-characterized probes for any region within the genome have emerged. Furthermore, the evolution of different multicolor fluorescence in situ hybridization (FISH) technologies now allows the cohybridization of multiple DNA-probes of different colors. These developments have paved the way for FISH-based automated karyotyping or the simultaneous analysis of multiple defined regions within the genome. Using appropriate instrumentation and image processing, the analysis can be performed two-dimensionally on metaphase spreads or three-dimensionally in intact interphase nuclei. Here we summarize some of the most recent developments and discuss the application of painting probes in different scenarios.

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References

  • Albertson DG, Pinkel D (2003) Genomic microarrays in human genetic disease and cancer. Hum Mol Genet 12 (Suppl 2): R145–52.

    Google Scholar 

  • Azofeifa J, Fauth C, Kraus J et al. (2000) An optimized probe set for the detection of small interchromosomal aberrations by 24-color FISH. Am J Hum Genet 66: 1684–1688.

    Google Scholar 

  • Barros RM, Nagamachi CY, Pieczarka JC et al. (2003) Chromosomal studies in Callicebus donacophilus pallescens, with classic and molecular cytogenetic approaches: multicolour FISH using human and Saguinus oedipus painting probes. Chromosome Res 11: 327–334.

    Google Scholar 

  • Bolzer A, Craig JM, Cremer T, Speicher MR (1999) A complete set of repeat-depleted, PCR-amplifiable, human chromosome-specific painting probes. Cytogenet Cell Genet 84: 233–240.

    Google Scholar 

  • Brown J, Saracoglu K, Uhrig S, Speicher MR, Eils R, Kearney L (2001) Subtelomeric chromosome rearrangements are detected using an innovative 12-colour FISH assay (MTEL). Nat Med 7: 497–501.

    Google Scholar 

  • Carter NP, Ferguson-Smith MA, Perryman MT et al. (1992) Reverse chromosome painting: a method for the rapid analysis of aberrant chromosomes in clinical cytogenetics. J Med Genet 29: 299–307.

    Google Scholar 

  • Cheung VG, Nowak N, Jang W et al. (2001) Integration of cytogenetic landmarks into the draft sequence of the human genome. Nature 409: 953–958.

    Google Scholar 

  • Chudoba I, Plesch A, Lörch T, Lemke J, Claussen U, Senger G (1999) High resolution multicolor-banding: a new technique for refined FISH analysis of human chromosomes. Cytogenet Cell Genet 84: 156–160.

    Google Scholar 

  • Collins C, Kuo WL, Segraves R, Fuscoe J, Pinkel D, Gray JW (1991) Construction and characterization of plasmid libraries enriched in sequences from single human chromosomes. Genomics 11: 997–1006.

    Google Scholar 

  • Craig JM, Kraus J, Cremer T (1997) Removal of repetitive sequences from FISH probes using PCR-assisted affinity chromatography. Hum Genet 100: 472–476.

    Google Scholar 

  • Cremer T, Cremer C, Baumann H et al. (1982) Rabl's model of the interphase chromosome arrangement tested in Chinese hamster cells by premature chromosome condensation and laser-UV-microbeam experiments. Hum Genet 60: 46–56.

    Google Scholar 

  • Cremer T, Lichter P, Borden J, Ward DC, Manuelidis L (1988) Detection of chromosome aberrations in metaphase and interphase tumor cells by in situ hybridization using chromosome-specific library probes. Hum Genet 80: 235–246.

    Google Scholar 

  • Cremer T, Cremer C (2001) Chromosome territories, nuclear architecture and gene regulation in mammalian cells. Nat Rev Genet 2: 292–301.

    Google Scholar 

  • Fauth C, Speicher MR (2001) Classifying by colors: FISH-based genome analysis. Cytogenet Cell Genet 93: 1–10.

    Google Scholar 

  • Fauth C, Zhang H, Harabacz S et al. (2001) A new strategy for the detection of subtelomeric rearrangements. Hum Genet 109: 576–583.

    Google Scholar 

  • Fiegler H, Gribble SM, Burford DC et al. (2003a) Array painting: a method for the rapid analysis of aberrant chromosomes using DNA microarrays. J Med Genet 40: 664–670.

    Google Scholar 

  • Fiegler H, Carr P, Douglas EJ et al. (2003b) DNA microarrays for comparative genomic hybridization based on DOP-PCR amplification of BAC and PAC clones. Genes Chromosomes Cancer 36: 361–374.

    Google Scholar 

  • Froenicke L, Anderson LK, Wienberg J, Ashley T (2002) Male mouse recombination maps for each autosome identified by chromosome painting. Am J Hum Genet 71: 1353–1368.

    Google Scholar 

  • Granzow M, Popp S, Keller M et al. (2003d) Multiplex FISH telomere integrity assay identifies an unbalanced cryptic translocation der (5)t(3;5)(q27;p15.3) in a family with three mentally retarded individuals. Hum Genet 107: 51–57.

    Google Scholar 

  • Gribble SM, Fiegler H, Burford DC et al. (2004) Applications of combined DNA microarray and chromosome sorting technologies. Chromosome Res 12: 35–43.

    Google Scholar 

  • Guan XY, Meltzer PS, Trent JM (1994) Rapid generation of whole chromosome painting probes (WCPs) by chromosome microdissection. Genomics 22: 101–107.

    Google Scholar 

  • Henegariu O, Artan S, Greally JM et al. (2001) Cryptic translocation identification in human and mouse using several telomeric multiplex FISH (TM-FISH) strategies. Lab Invest 81: 483–491.

    Google Scholar 

  • Jauch A, Wienberg J, Stanyon R et al. (1992) Reconstruction of genomic rearrangements in great apes and gibbons by chromosome painting. Proc Natl Acad Sci USA 89: 8611–8615.

    Google Scholar 

  • Jentsch I, Adler ID, Carter NP, Speicher MR (2001) Karyotyping mouse chromosomes by multiplex-FISH (M-FISH). Chrom Res 9: 211–214.

    Google Scholar 

  • Karhu R, Ahlstedt-Soini M, Bittner M, Meltzer P, Trent JM, Isola JJ (2001) Chromosome arm-specific multicolor-FISH. Genes Chromosomes Cancer 30: 105–109.

    Google Scholar 

  • Klein CA, Schmidt-Kittler O, Schardt JA, Pantel K, Speicher MR, Riethmüller G (1999) Comparative genomic hybridization, loss of heterozygosity, and DNA sequence analysis of single cells. Proc Natl Acad Sci USA 96: 4494–4499.

    Google Scholar 

  • Klein CA, Blankenstein TJ, Schmidt-Kittler O et al. (2002) Genetic heterogeneity of single disseminated tumour cells in minimal residual cancer. Lancet 360: 683–689.

    Google Scholar 

  • Kraus J, Lederer G, Keri C et al. (2003a) A familial unbalanced subtelomeric translocation resulting in a monosomy 6q27!qter. J Med Genet 40: e48

    Google Scholar 

  • Kraus J, Cohen M, Speicher MR (2003b) Multicolor-FISH fine-mapping unravels an insertion as a complex chromosomal rearrangement involving 6 breakpoints and a 5.89 Mb large deletion. J Med Genet 40: e60

    Google Scholar 

  • Lacoste TD, Michalet X, Pinaud F, Chemla DS, Alivisatos AP, Weiss S (2000) Ultrahigh-resolution multicolor colocalization of single fluorescent probes. Proc Natl Acad Sci USA 97: 9461–9466.

    Google Scholar 

  • Landegent JE, Jansen in de Wal N, Dirks RW, Baas F, van der Ploeg M (1987) Use of whole cosmid cloned genomic sequences for chromosomal localization by non-radioactive in situ hybridization. Hum Genet 77: 366–370.

    Google Scholar 

  • Langer S, Fauth C, Rocchi M, Murken J, Speicher MR (2001a) AcroM-FISH analyses of marker chromosomes. Hum Genet 109: 152–158.

    Google Scholar 

  • Langer S, Jentsch I, Gangnus R, Yan H, Lengauer C, Speicher MR (2001b) Facilitating haplotype analysis by fully automated analysis of all chromosomes in human-mouse hybrid cell lines. Cytogenet Cell Genet 93: 11–15.

    Google Scholar 

  • Lengauer C, Speicher MR, Popp S et al. (1993) Chromosomal bar codes constructed by fluorescence in situ hybridization with Alu-PCR products of multiple YAC clones. Hum Mol Genet 2: 505–512.

    Google Scholar 

  • Lichter P, Cremer T, Borden J, Manuelidis L, Ward DC (1988) Delineation of individual human chromosomes in metaphase and interphase cells by in situ suppression hybridization using recombinant DNA libraries. Hum Genet 80: 224–234.

    Google Scholar 

  • Liyanage M, Coleman A, du Manoir S et al. (1996) Multicolor spectral karyotyping of mouse chromosomes. Nat Genet 14: 312–315.

    Google Scholar 

  • Lizardi PM, Huang X, Zhu Z et al. (1998) Mutation detection and single-molecule counting using isothermal rolling-circle amplification. Nat Genet 19: 225–232.

    Google Scholar 

  • Maierhofer C, Jentsch I, Lederer G, Fauth C, Speicher MR (2002) Multicolor-FISH in two and three dimensions for clastogenic analyses. Mutagenesis 17: 523–527.

    Google Scholar 

  • Malmgren H, Sahlen S, Inzunza J et al. (2002) Single cell CGH analysis reveals a high degree of mosaicism in human embryos from patients with balanced structural chromosome aberrations. Mol Hum Reprod 8: 502–510.

    Google Scholar 

  • Müller S, O'Brien PC, Ferguson-Smith MA, Wienberg J (1997a) A novel source of highly specific chromosome painting probes for human karyotype analysis derived from primate homologues. Hum Genet 101: 149–153.

    Google Scholar 

  • Müller S, Rocchi M, Ferguson-Smith MA, Wienberg J (1997b) Toward a multicolor chromosome bar code for the entire human karyotype by fluorescence in situ hybridization. Hum Genet 100: 271–278.

    Google Scholar 

  • Müller S, O'Brien PC, Ferguson-Smith MA, Wienberg J (1998) Cross-species colour segmenting: a novel tool in human karyotype analysis. Cytometry 33: 445–452.

    Google Scholar 

  • Müller S, Neusser M, Wienberg J (2002) Towards unlimited colors for fluorescence in situ hybridization (FISH). Chrom Res 10: 223–232.

    Google Scholar 

  • Pinkel D, Landegent J, Collins C et al. (1988) Fluorescence in situ hybridization with human chromosome-specific libraries: detection of trisomy 21 and translocations of chromosome 4. Proc Natl Acad Sci USA 85: 9138.

    Google Scholar 

  • Pinkel D, Segraves R, Sudar D et al. (1998) High resolution analysis of DNA copy number variations using comparative genomic hybridization to microarrays. Nat Genet 20: x207–211.

    Google Scholar 

  • Scherthan H, Cremer T, Arnason U, Weier HU, Lima-de-Faria A, Frönicke L (1994) Comparative chromosome painting discloses homologous segments in distantly related mammals. Nat Genet 6: 342–347.

    Google Scholar 

  • Schmidt-Kittler O, Ragg T, Daskalakis A et al. (2003) From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc Natl Acad Sci USA 100: 7737–7742.

    Google Scholar 

  • Schröck E, du Manoir S, Veldman T et al. (1996) Multicolor spectral karyotyping of human chromosomes.Science 273: 494–497.

    Google Scholar 

  • Schröck E, Veldman T, Padilla-Nash H et al. (1997) Spectral karyotyping refines cytogenetic diagnostics of constitutional chromosomal abnormalities. Hum Genet 101: 255–262.

    Google Scholar 

  • Snijders AM, Nowak N, Segraves R et al. (2001) Assembly of microarrays for genome-wide measurement of DNA copy number. Nat Genet 29: 263–264.

    Google Scholar 

  • Solinas-Toldo S, Lampel S, Stilgenbauer S et al. (1997) Matrixbased comparative genomic hybridization: biochips to screen for genomic imbalances. Genes Chromosomes Cancer 20: 399–407.

    Google Scholar 

  • Speicher MR, Ballard SG, Ward DC (1996) Karyotyping human chromosomes by combinatorial multi-fluor FISH. Nat Genet 12: 368–375.

    Google Scholar 

  • Speleman F, Leroy JG, Van Roy N et al. (1991) Pallister-Killian syndrome: characterization of the isochromosome 12p by fluorescent in situ hybridization. Am J Med Genet 41: 381–387.

    Google Scholar 

  • Taneja KL, Chavez EA, Coull J, Lansdorp PM (2001) Multicolor fluorescence in situ hybridization with peptide nucleic acid probes for enumeration of specific chromosomes in human cells. Genes Chromosomes Cancer 30: 57–63.

    Google Scholar 

  • Tanke HJ, Wiegant J, van Gijlswijk RPM et al. (1999) New strategy for multi-colour fluorescence in situ hybridisation: COBRA: COmbined Binary RAtio labelling. Eur J Hum Genet 7: 2–11.

    Google Scholar 

  • Telenius H, Pelmear AH, Tunnacliffe A et al. (1992) Cytogenetic analysis by chromosome painting using DOPPCR-amplified flow-sorted chromosomes. Genes Chromosomes Cancer 4: 257–263.

    Google Scholar 

  • Uhrig S, Schuffenhauer S, Fauth C et al. (1999) Multiplex-FISH (M-FISH) for pre-and postnatal diagnostic applications. Am J Hum Genet 65: 448–462.

    Google Scholar 

  • Veldman T, Vignon C, Schröck E, Rowley JD, Ried T (1997) Hidden chromosome abnormalities in haematological malignancies detected by multicolour spectral karyotyping. Nat Genet 15: 406–410.

    Google Scholar 

  • Voullaire L, Wilton L, Slater H, Williamson R (1999) Detection of aneuploidy in single cells using comparative genomic hybridization. Prenat Diagnosis 19: 846–851.

    Google Scholar 

  • Wells D, Sherlock JK, Handyside AH, Delhanty JD (1999) Detailed chromosomal and molecular genetic analysis of single cells by whole genome amplification and comparative genomic hybridisation. Nucleic Acids Res 27: 1214–1218.

    Google Scholar 

  • Wiegant J, Bezrookove V, Rosenberg C et al. (2000) Differentially painting human chromosome arms with combined binary ratio-labeling fluorescence in situ hybridization. Genome Res 10: 861–865.

    Google Scholar 

  • Zhong XB, Lizardi PM, Huang XH, Bray-Ward PL, Ward DC (2001) Visualization of oligonucleotide probes and point mutations in interphase nuclei and DNA fibers using rolling circle DNA amplification. Proc Natl Acad Sci USA 98: 3940–3945.

    Google Scholar 

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Langer, S., Kraus, J., Jentsch, I. et al. Multicolor chromosome painting in diagnostic and research applications. Chromosome Res 12, 15–23 (2004). https://doi.org/10.1023/B:CHRO.0000009326.21752.88

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