Detection of Chromosomal Aneuploidy Using Exome Sequencing

Abstract

Background: Chromosomal aneuploidy, characterized by an abnormal number of chromosomes, represents a significant cause of genetic disorders. While karyotyping and chromosomal microarray analysis (CMA) are established diagnostic approaches, they are limited by cost and extended turnaround times. Advances in exome sequencing (ES) bioinformatics enable detection of chromosomal aneuploidy alongside single-nucleotide variant analysis. This study explores the utility of clinical ES for the detection of aneuploidies. Method: We analyzed exome sequencing data (2023-2024) from samples positive for Trisomy 21 (n = 27), Trisomy 18 (n = 4), Turner syndrome (n = 3), and Klinefelter syndrome (n = 2) from our clinical ES cohort (n = 10,000). Results: The results obtained were concordant with copy number variants (CNVs) identified by clinical testing. Conclusion: In conclusion, our findings suggest that exome sequencing offers a rapid and viable approach for the detection of chromosomal aneuploidy, potentially reducing turnaround time and associated costs.

Keywords: aneuploidy; chromosome; copy number variation (CNV); exome sequencing (ES); trisomy.

Figure 1

(A) A quantitative analysis of detected aneuploidy cases alongside the proportion of these cases that were clinically suspected by a physician. The “Detected Rate per Aneuploidy” refers to the total number of times a specific chromosomal abnormality was identified within the study cohort. The “Rate of Suspected Aneuploidy by Physician” indicates the subset of these detected cases where a physician had a pre-existing clinical suspicion of aneuploidy prior to definitive diagnosis. (B) Percentage of Aneuploidy Types Detected in the study.