Recent advances in the detection technologies for balanced chromosomal rearrangements.

Balanced chromosomal rearrangements (BCRs) refer to a type of chromosomal structural variations without chromosomal gains or losses. BCR carriers may experience fertility issues, including a higher risk of infertility, recurrent miscarriages, or having offspring with chromosomal abnormalities. Since there are no apparent gains or losses of genetic materials in BCR carriers, their detection has long been a focal and challenging issue in the field of chromosomal structural variation analysis. Karyotyping cannot detect submicroscopic rearrangements because of restricted resolution and the application of fluorescence in situ hybridization (FISH) is limited by the necessity of a known loci. Chromosomal microarray analysis and standard short-read sequencing, widely used in clinical practice, cannot detect BCRs. In summary, the clinical detection techniques are unable to accurately identify the breakpoints of BCRs. The improved short-read sequencing such as mate-pair sequencing has been found to detect balanced rearrangements. Emerging advanced technologies such as long-read sequencing, and optical genome mapping, have already shown their potential in detecting BCRs. This review primarily elucidates the principles, applicability, advantages, and limitations of the detection techniques for BCRs, aiming to assist in the early identification and appropriate advice of patients with BCRs in genetic counseling.