Lekárska genetika a diagnostika 2/2024

Pathological and technological aspects of genomic copy number variant analysis

Unbalanced structural DNA aberrations, also known as copy number variants (CNVs), are one of the fundamental aspects of understanding population diversity and disease development, including typical monogenic disorders, but also complex diseases with multifactorial etiology. In this review, we summarize the current knowledge of the mutational mechanisms related to DNA replication and repair involved in the development of CNVs and point out the parallels between the evolutionary and pathological aspects of this type of genetic variability. We discuss the methodological progress that led to the development of state-of-the-art technologies enabling the detection of CNVs together with other types of genetic variants at the whole-genome level within a single analysis. In conclusion, we emphasize the current challenges of clinical genetics associated with the interpretation of CNV findings, which is crucial for their effective use in clinical practice.

Keywords: copy number variants, pathomechanisms, chromoanagenesis, CNV detection, CNV interpretation