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Micro-array analyses decipher exceptional complex familial chromosomal rearrangement

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Abstract

Recently there has been an increased interest in large-scale genomic variation and clinically in the consequences of haploinsufficiency of genomic segments or disruption of normal gene function by chromosome rearrangements. Here, we present an extraordinary case in which both mother and daughter presented with unexpected chromosomal rearrangement complexity, which we characterized with array-CGH, array painting and multicolor large insert clone hybridizations. We found the same 12 breakpoints involving four chromosomes in both mother and daughter. In addition, the daughter inherited a microdeletion from her father. We mapped all breakpoints to the resolution level of breakpoint spanning clones. Genes were found within 7 of the 12 breakpoint regions, some of which were disrupted by the chromosome rearrangement. One of the rearrangements disrupted a locus, which has been discussed as a quantitative trait locus for fetal hemoglobin expression in adults. Interestingly, both mother and daughter show persistent fetal hemoglobin levels. We detail the most complicated familial complex chromosomal rearrangement reported to date and thus an extreme example of inheritance of chromosomal rearrangements without error in meiotic segregation.

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Acknowledgements

We thank Drs. J. Benet and J. Navarro (both Universitat Autònoma de Barcelona, Spain) for their helpful comments on the manuscript. This work was supported by the Deutsche Forschungsgemeinschaft (Sp 460/4-1) and the Bundesministerium für Bildung und Forschung (NGFN).

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Author notes

  1. Christine Fauth

    Present address: Dept. für Med. Genetik, Mol. und Klin. Pharmakologie Med., Universität Innsbruck, Schoepfstr. 41, 6020, Innsbruck, Austria

Authors and Affiliations

  1. Institut für Humangenetik, Technische Universität München, Trogerstr. 32, 81675, München, Germany

    Christine Fauth, Jürgen Kraus & Michael R. Speicher

  2. Institut für Humangenetik, GSF-Forschungszentrum für Umwelt und Gesundheit, Ingolstädter Landstr. 1, 85764, Neuherberg, Germany

    Christine Fauth, Jürgen Kraus & Michael R. Speicher

  3. Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute, Hinxton, CB10 1SA, Cambridge, UK

    Susan M. Gribble, Keith M. Porter, Bee Ling Ng, Heike Fiegler & Nigel P. Carter

  4. Unitat Biologia Cel.lular i Genètica Mèdica, Facultat Medicina, Dept. Biologia Cel.lular, Fisiologia i Immunologia, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Montserrat Codina-Pascual

  5. Institut für Humangenetik, Justus-Liebig-Universität, Schlangenzahl 14, 35392, Giessen, Germany

    Sabine Uhrig

  6. Kinderklinik München Schwabing, Technische Universität München, Kölner Platz 1, 80804, München, Germany

    Jürgen Leifheit

  7. Institut für Humangenetik, Johannes Gutenberg-Universität Mainz, 55101, Mainz, Germany

    Thomas Haaf

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  1. Christine Fauth
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  2. Susan M. Gribble
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  11. Nigel P. Carter
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Correspondence to Michael R. Speicher.

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Fauth, C., Gribble, S.M., Porter, K.M. et al. Micro-array analyses decipher exceptional complex familial chromosomal rearrangement. Hum Genet 119, 145–153 (2006). https://doi.org/10.1007/s00439-005-0103-z

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  • DOI: https://doi.org/10.1007/s00439-005-0103-z

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