TY - JOUR
T1 - Genomic Characterization of Chromosomal Insertions
T2 - Insights into the Mechanisms Underlying Chromothripsis
AU - Kato, Takema
AU - Ouchi, Yuya
AU - Inagaki, Hidehito
AU - Makita, Yoshio
AU - Mizuno, Seiji
AU - Kajita, Mitsuharu
AU - Ikeda, Toshiro
AU - Takeuchi, Kazuhiro
AU - Kurahashi, Hiroki
N1 - Publisher Copyright:
© 2017 S. Karger AG, Basel.
PY - 2018/1/1
Y1 - 2018/1/1
N2 - Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage.
AB - Chromosomal insertions are rare structural rearrangements, and the molecular mechanisms underlying their origin are unknown. In this study, we used whole genome sequencing to analyze breakpoints and junction sequences in 4 patients with chromosomal insertions. Our analysis revealed that none of the 4 cases involved a simple insertion mediated by a 3-chromosomal breakage and rejoining events. The inserted fragments consisted of multiple pieces derived from a localized genomic region, which were shuffled and rejoined in a disorderly fashion with variable copy number alterations. The junctions were blunt ended or with short microhomologies or short microinsertions, suggesting the involvement of nonhomologous end-joining. In one case, analysis of the parental origin of the chromosomes using nucleotide variations within the insertion revealed that maternal chromosomal segments were inserted into the paternal chromosome. This patient also carried both maternal alleles, suggesting the presence of zygotic trisomy. These data indicate that chromosomal shattering may occur in association with trisomy rescue in the early postzygotic stage.
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U2 - 10.1159/000481586
DO - 10.1159/000481586
M3 - Article
C2 - 29073611
AN - SCOPUS:85032359721
SN - 1424-8581
VL - 153
SP - 1
EP - 9
JO - Cytogenetic and Genome Research
JF - Cytogenetic and Genome Research
IS - 1
ER -