Long‐read Oxford nanopore sequencing reveals a de novo case of complex chromosomal rearrangement involving chromosomes 2, 7, and 13. Issue 9 (27th June 2022)

• Record Type: Journal Article
• Authors: Xing, Lingling; Shen, Ying; Wei, Xiang; Luo, Yuan; Yang, Yan; Liu, Haipeng; Liu, Hongqian
• Is Part Of: Molecular genetics & genomic medicine. Volume 10:Issue 9(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-06-27
• Subjects: complex chromosomal rearrangements (CCRs) -- karyotype analysis of chromosome G‐banding karyotype analysis (550 bands) -- long‐read sequencing Oxford nanopore technology -- third‐generation sequencing (TGS); Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.2011
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Complex chromosomal rearrangements (CCRs) are associated with high reproductive risk, infertility, abnormalities in offspring, and recurrent miscarriage in women. It is essential to accurately characterize apparently balanced chromosome rearrangements in unaffected individuals. Methods: A CCR young couple who suffered two spontaneous abortions and underwent labor induction due to fetal chromosomal abnormalities was studied using long‐read sequencing(LRS), single‐nucleotide polymorphism (SNP) array, G‐banding karyotype analysis (550‐band resolution), and Sanger sequencing. Results: SNP analysis of the amniotic fluid cells during the third pregnancy revealed a 9.9‐Mb duplication at 7q21.11q21.2 and a 24.8‐Mb heterozygous deletion at 13q21.1q31.1. The unaffected female partner was a carrier of a three‐way CCR [46, XX, ? ins(7;13)(q21.1;q21.1q22)t(2;13)(p23;q22)]. Subsequent LRS analysis revealed the exact breakpoint locations on the derivative chromosomes and the specific method of chromosome rearrangement, indicating that the CCR carrier was a more complex structural rearrangement comprising five breakpoints. Furthermore, LRS detected an inserted fragment of chromosome 13 in chromosome 7. Conclusions: LRS is effective for analyzing the complex structural variations of the human genome and may be used to clarify the specific CCRs for effective genetic counseling and appropriate intervention. Abstract : This study investigated a de novo case of complex chromosomal rearrangement (CRR) in a young couple visited our hospital for genetic counseling and fertility guidance due to the increased thickness of the fetal nuchal translucency. We successfully identified the female partner as a carrier of a three‐way CCR [46, XX, ? ins(7; 13)(q21.1;q21.1q22)t(2;13)(p23;q22)] using high‐resolution G‐banding karyotype analysis (550‐band resolution). Third‐generation sequencing (TGS) using PromethION platform revealed that the five breakpoints on chromosomes 2, 7, and 13 (2:18044504, 7:82511487, 7:92482297, 13:56958850, and 13:81861586) participated in the CCR.