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 - Funding Information:
We thank the patients and their families who participated in this study. We also thank Drs. Kazuhiro Matsuda and Masanobu Ito for providing samples as well as Ms. Makiko Tsutsumi, Naoko Fujita, and Asami Kuno for technical assistance. This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (15K19042 to T.K., 15H04710 and 24390085 to H.K.) and from the Ministry of Health, Welfare and Labor (16ek0109067h0003 to H.K.).
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
VL - 153
SP - 1
EP - 9
JO - Cytogenetic and Genome Research
JF - Cytogenetic and Genome Research
SN - 1424-8581
IS - 1
ER -