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Familial transmission of chromoanagenesis leads to unpredictable unbalanced rearrangements through meiotic recombination
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  • Julie Masson,
  • Céline Pebrel-Richard,
  • Matthieu Egloff,
  • MATHILDE FRETIGNY,
  • Marion Beaumont,
  • Kevin Uguen,
  • Pierre-Antoine Rollat-Farnier,
  • Flavie Diguet,
  • Isabelle Perthus,
  • Gwenaël LE GUYADER,
  • Damien Haye,
  • Marie-Noëlle Bonnet Dupeyron,
  • Audrey Putoux,
  • Fabienne Raskin-Champion,
  • Marianne Till,
  • Nicolas CHATRON,
  • Bérénice Doray,
  • Claire Bardel,
  • CHRISTINE VINCIGUERRA,
  • Damien Sanlaville,
  • Caroline Schluth-Bolard
Julie Masson
Hospices Civils de Lyon Centre de pathologie et biologie Est

Corresponding Author:[email protected]

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Céline Pebrel-Richard
Centre Hospitalier Universitaire de Clermont-Ferrand
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Matthieu Egloff
Centre Hospitalier Universitaire de Poitiers
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MATHILDE FRETIGNY
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Marion Beaumont
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Kevin Uguen
CHU Brest Inserm Univ Brest EFSUMR 1078 GGB Brest France
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Pierre-Antoine Rollat-Farnier
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Flavie Diguet
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Isabelle Perthus
Centre Hospitalier Universitaire de Clermont-Ferrand
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Gwenaël LE GUYADER
Centre Hospitalier Universitaire de Poitiers
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Damien Haye
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Marie-Noëlle Bonnet Dupeyron
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Audrey Putoux
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Fabienne Raskin-Champion
Centre Hospitalier Lyon-Sud
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Marianne Till
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Nicolas CHATRON
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Bérénice Doray
Hopitaux universitaires de Strasbourg
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Claire Bardel
Hospices Civils de Lyon Centre de pathologie et biologie Est
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CHRISTINE VINCIGUERRA
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Damien Sanlaville
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Caroline Schluth-Bolard
Hospices Civils de Lyon Centre de pathologie et biologie Est
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Abstract

Chromoanagenesis are complex chromosomal rearrangements that are supposed to occur during a single catastrophic event. They may result in loss or gain of genetic material and may be responsible for various phenotypes. These rearrangements are usually sporadic. However, some familial cases have been reported. Here, we studied six families in which a healthy parent carrying a chromoanagenesis transmitted its rearrangement in an unbalanced manner to its descent. The rearrangements were characterized by karyotype, fluorescent in situ hybridization, chromosomal microarray and whole genome sequencing (WGS) in the parents and their offspring. We then hypothesized meiosis-pairing figures of parental chromosomes that may have led to meiotic recombination between normal and abnormal homologous chromosomes, resulting in the formation of new unbalanced rearrangements. This work underlines that chromoanagenesis can be associated with a normal phenotype and a normal fertility, even in males, and that WGS may be the unique way to identify these rearrangements in some cases. Chromoanagenesis can be transmitted in an unbalanced and unpredictable way because of meiotic recombination. Thus, genetic counseling and technical choice for prenatal diagnosis are complex. Finally this work questions the meiotic pairing mechanisms of complex rearrangements, still poorly understood.