Small supernumerary marker chromosomes: A legacy of trisomy rescue?

Abstract

We studied by a whole genomic approach and trios genotyping, 12 de novo, nonrecurrent 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 nondisjunction followed by postzygotic anaphase lagging of the supernumerary chromosome and its subsequent chromothripsis.

Rare partial trisomy and tetrasomy of 15q11-q13 associated with developmental delay and autism spectrum disorder

“…Most sSMCs are caused by a multiple-step mechanism: firstly, maternal meiotic nondisjunction, and then postzygotic anaphase lagging of the SMC and its subsequent chromothripsis [16]. The sSMCs Dup15q is characterized by hypotonia motor delays, autism spectrum disorder (ASD), intellectual disability, and epilepsy including infantile spasms.…”

“…CNV-Seq showed a 10. 16 this difference may be that the theories are different between these two technologies: SNP array is a microarray-based method while CNV-Seq is based on next-generation sequencing. The number of probes and DNA segments on a microarray does not represent the true copy number of sequences in an assembled genome.…”

De Novo Small Supernumerary Marker Chromosomes Arising From Partial Trisomy Rescue

“…However, when the process of chromothripsis is interrupted, it can cause partial chromosomal loss and/or rearrangements with or without UPD ( Figure 1A) (Liehr, 2010). Co-occurrence of de novo CCRs and UPD, particularly those involving a set of homologous chromosomes, is indicative of incomplete trisomy rescue (Liehr et al, 2011;Kurtas et al, 2019). Previous studies have shown that a substantial proportion of UPD cases were accompanied by additional genomic or cytogenetic abnormalities (Liehr, 2010).…”

“…Recent studies have suggested that de novo non-recurrent small SMCs result from incomplete trisomy rescue (Kurtas et al, 2019). Trisomy rescue is a physiological phenomenon to eliminate excessive chromosomes from trisomic cells (Fenech et al, 2011;Jones et al, 2012).…”

“…Trisomy rescue is a physiological phenomenon to eliminate excessive chromosomes from trisomic cells (Fenech et al, 2011;Jones et al, 2012). When trisomy rescue is interrupted before complete elimination of target chromosomes, it may create various chromosomal rearrangements including small SMCs (Liehr, 2010;Kurtas et al, 2019). In this Perspective article, we discuss the underlying mechanisms and clinical significance of trisomy rescue in association with SMCs and other complex chromosomal rearrangements (CCRs).…”