Abstract
In line with the intentions of an issue celebrating the 50th anniversary of Human Genetics, we focus on a series of frequently cited studies published in this journal during the 1980s and 1990s. These studies have contributed to the rise of molecular cytogenetics. They yielded evidence that chromosomes occupy distinct territories in the mammalian cell nucleus, first obtained with laser-UV-microbeam experiments and thereafter with chromosome painting, and contributed to the development of interphase cytogenetics and comparative genome hybridization. We provide a personal account of experimental concepts, which were developed by us and others, and describe some of the unforeseeable turns and obstacles, which we had to overcome on the way towards an experimental realization. We conclude with a perspective on current developments and goals of molecular cytogenetics.
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Acknowledgments
Our scientific journey (and our careers) would have failed without the essential ideas, the experimental skills and the continuous support of colleagues and friends. The support of Winfried Krone, Ulrich Wolf and Helmut Baitsch was essential to form a little laser UV-microbeam research group in the early 1970s at the Institute of Anthropology and Human Genetics of the University of Freiburg i. Br.. TC and CC wish to thank, in particular, Christian Zorn and Jürgen Zimmer for their invaluable contributions to our early UV-microbeam studies of nuclear architecture. TC is indebted to his mentor Friedrich Vogel, director of the Institute of Human Genetics and Anthropology of the University of Heidelberg from 1962 to 1993, for his unfailing support in critical times, and to Traute Schroeder-Kurth, for the opportunity to establish his own laboratory within the Institute’s Divison of Cytogenetics directed by her. Opportunities to work as guest researchers in laboratories providing conceptual and experimental expertise in cutting-edge technologies mark turning points in our scientific endeavors. CC thanks Marvin A. van Dilla and Joe W. Gray for the opportunity to work with them at the Biomedical Sciences Division of the Lawrence Livermore National Laboratories on the sorting of the human Y chromosome. TC and PL greatly acknowledge support from Laura Manuelidis and David C. Ward. Chromosome painting and the direct demonstration of chromosome territories were achieved together with them in their laboratories at Yale University. In addition, TC thanks Michael W. Berns (University of California, Irvine), Wolfgang Hennig and Peter H. Vogt (then University of Nijmegen), Mels van der Ploeg (University of Leiden), Maynard V. Olson and Harold C. Riethman (then Washington University, St. Louis) for making it possible to learn and perform bench work in their laboratories. Interphase cytogenetics was introduced during the 1980s in TC’s Heidelberg laboratory with support from Peter Pearson, Mels van der Ploeg and their co-workers and essential, experimental contributions (in alphabetical order) from Marion Cremer, Patricia Emmerich, Anna Jauch, Christoph Lengauer, Susanne Popp, Gudrun Rappold and Margit Schardin. The application of chromosome painting as a tool to study chromosomal rearrangements during evolution was initiated by Johannes Wienberg. Daniela Zink performed the first studies of chromosome territories in living cells. The concept of CGH was realized and applied to tumor samples in the TC and PL laboratories with the help of numerous colleagues, including (again in alphabetical order) Stanislas du Manoir, Stefan Joos, Thomas Ried, Harry Scherthan, Evelin Schröck, Michael Speicher and Ruthhild Weber. A first realization of the concept of array CGH (or matrix-based CGH as we originally called this method) was achieved in the laboratory of PL with major impact from Sabina Solinas-Toldo and colleagues. Finally, we wish to thank the Deutsche Forschungsgemeinschaft (DFG), who supported our work with fellowships and grants. Walther Klofat represented for us the good spirit of the DFG in person. Excerpts cited from grant applications, letters and unpublished manuscripts written in German were translated in English from TC.
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Cremer, T., Cremer, C. & Lichter, P. Recollections of a scientific journey published in human genetics: from chromosome territories to interphase cytogenetics and comparative genome hybridization. Hum Genet 133, 403–416 (2014). https://doi.org/10.1007/s00439-014-1425-5
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DOI: https://doi.org/10.1007/s00439-014-1425-5