Small supernumerary marker chromosomes: A legacy of trisomy rescue?

Kurtas N. E.;Xumerle L.;Leonardelli L.;Delledonne M.;Brusco A.;Chrzanowska K.;Schinzel A.;Larizza D.;Guerneri S.;Natacci F.;Bonaglia M. C.;REHO, PAOLO;Manolakos E.;Mattina T.;Soli F.;Provenzano A.;Al-Rikabi A. H.;ERRICHIELLO, ELVIRA;Nazaryan-Petersen L.;Giglio S.

Membro del Collaboration Group

;Tommerup N.;Liehr T.;Zuffardi O.

2019-01-01

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Abstract

We studied by a whole genomic approach and trios genotyping, 12 de novo, non-recurrent small supernumerary marker chromosomes (sSMC), detected as mosaics during pre- or postnatal diagnosis and associated with increased maternal age. Four sSMCs contained pericentromeric portions only, whereas eight had additional non-contiguous portions of the same chromosome, assembled together in a disordered fashion by repair-based mechanisms in a chromothriptic event. Maternal hetero/isodisomy was detected with a paternal origin of the sSMC in some cases, whereas in others two maternal alleles in the sSMC region and biparental haplotypes of the homologs were detected. In other cases the homologs were biparental while the sSMC had the same haplotype of the maternally inherited chromosome. These findings strongly suggest that most sSMCs are the result of a multiple-step mechanism, initiated by maternal meiotic non-disjunction followed by post-zygotic anaphase lagging of the supernumerary chromosome and its subsequent chromothripsis.