The Genetics and Prenatal Diagnosis Center, The Department of Obstetrics and Gynecology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
GrandOmics Diagnostic, Wuhan, China.
Mol Genet Genomic Med. 2022 Jun;10(6):e1936. doi: 10.1002/mgg3.1936. Epub 2022 Apr 6.
Balanced reciprocal translocation is one of the most common chromosomal abnormalities in humans that may lead to infertility, recurrent pregnancy loss, or having children with physical or mental abnormalities. Karyotyping and FISH are traditional detection approaches with a low resolution. Bionano optical genome mapping (OGM) developed in recent years can be used to analyze chromosomal abnormalities at a higher resolution, providing the possibility of more in-depth analyses of balanced chromosome translocations.
To evaluate the feasibility of OGM to detect chromosome balanced translocations, 10 genetic outpatients were collected and detected simultaneously by karyotype analysis, FISH, CNV-seq, and Bionano OGM in this study.
The results showed that the karyotypes of the patients were detected by karyotype analysis, FISH, and Bionano OGM, but one patient with karyotype t(Y,19) was not correctly detected by OGM. There were not find any chromosome abnormality by CNV-seq. More importantly, OGM allowed the location of the mutation to the gene level, which is important for aiding diagnoses, compared to karyotype analysis, and FISH.
This study shows that OGM can be a high adjunctive diagnostic method for detecting balanced chromosome translocations, but the accuracy and precision of OGM detecting mutations need to be gradually improved in telomere and centromere regions.
平衡易位是人类中最常见的染色体异常之一,可能导致不孕、反复流产,或生育身体或精神异常的孩子。核型分析和 FISH 是传统的低分辨率检测方法。近年来开发的 Bionano 光学基因组图谱(OGM)可用于更高分辨率地分析染色体异常,为深入分析平衡染色体易位提供了可能。
为评估 OGM 检测染色体平衡易位的可行性,本研究同时对 10 名遗传门诊患者进行了核型分析、FISH、CNV-seq 和 Bionano OGM 检测。
结果表明,通过核型分析、FISH 和 Bionano OGM 检测到了患者的核型,但 OGM 未能正确检测到核型为 t(Y,19)的患者。CNV-seq 未发现任何染色体异常。更重要的是,OGM 可以将突变定位到基因水平,与核型分析和 FISH 相比,这对辅助诊断很重要。
本研究表明,OGM 可以作为一种高辅助诊断方法,用于检测平衡染色体易位,但在端粒和着丝粒区域,OGM 检测突变的准确性和精度需要逐步提高。