Rodrigues Priscila Soares, Burssed Bruna, Bellucco Fernanda, Rosolen Débora Cristina Batista, Kim Chong Ae, Melaragno Maria Isabel
Genetics Division, Universidade Federal de São Paulo, São Paulo, Brazil.
Genetics Unit, Instituto da Criança, Universidade de São Paulo, São Paulo, Brazil.
Sci Rep. 2025 Apr 9;15(1):12191. doi: 10.1038/s41598-025-97077-1.
Chromosomal rearrangements involving additional material in individuals with phenotypic alterations usually result in partial trisomy, often accompanied by partial monosomy. To characterize chromosomal rearrangements and analyze genomic characteristics in the breakpoint regions in 31 patients with additional material on an autosomal chromosome. Different tests were performed to characterize these patients, including karyotyping, chromosomal microarray analysis (CMA), and fluorescent in situ hybridization (FISH). In silico analyses evaluated A/B chromosomal compartments, segmental duplications, and repetitive elements at breakpoints. The 31 rearrangements resulted in 47 copy number variations (CNVs) and a range of structural aberrations were identified, including six tandem duplications, 19 derivative chromosomes, two intrachromosomal rearrangements, one recombinant, two dicentric chromosomes, and one triplication. A deleted segment was associated with the duplication in 16 of the 19 patients with derivative chromosomes from translocation. Among the trios whose chromosome rearrangement origin could be investigated, 54,5% were de novo, 31,9% were maternally inherited, and 13,6% were paternally inherited from balanced translocations or inversion. Breakpoint analysis revealed that 22 were in the A compartment (euchromatin), 25 were in the B compartment (heterochromatin), and five were in an undefined compartment. Additionally, 14 patients had breakpoints in regions of segmental duplications and repeat elements. Our study found that a deletion accompanied by additional genetic material was present in 51.6% of the patients, uncovering the underlying genetic imbalances. Statistical analyses revealed a positive correlation between chromosome size and the occurrence of CNVs in the rearrangements. Furthermore, no preference was observed for breakpoints occurring in compartments A and B, repetitive elements, or segmental duplications.
在具有表型改变的个体中,涉及额外物质的染色体重排通常导致部分三体性,常伴有部分单体性。为了表征31例常染色体上有额外物质的患者的染色体重排并分析断点区域的基因组特征,我们进行了不同的检测来对这些患者进行表征,包括核型分析、染色体微阵列分析(CMA)和荧光原位杂交(FISH)。通过计算机分析评估了A/B染色体区室、节段性重复和断点处的重复元件。这31种重排导致了47个拷贝数变异(CNV),并鉴定出一系列结构畸变,包括6个串联重复、19条衍生染色体、2个染色体内重排、1个重组体、2条双着丝粒染色体和1个三倍体。在19例因易位产生衍生染色体的患者中,有16例的缺失片段与重复相关。在可研究染色体重排起源的三联体中,54.5%是新发的,31.9%是母系遗传的,13.6%是父系从平衡易位或倒位遗传的。断点分析显示,22个位于A区室(常染色质),25个位于B区室(异染色质),5个位于未定义区室。此外,14例患者的断点位于节段性重复和重复元件区域。我们的研究发现,51.6%的患者存在伴有额外遗传物质的缺失,揭示了潜在的遗传失衡。统计分析显示,染色体大小与重排中CNV的发生呈正相关。此外,未观察到断点在A区室和B区室、重复元件或节段性重复中的偏好。