What Exactly is Copy Number Variation?

Copy number variants (CNVs) were first characterized in 2006 as segments of DNA that repeat more than 1 kb compared to a reference genome. However, the Copy Number Variation Project expanded this definition, categorizing CNVs as variations that can range from 10 kb to 5,000 kb, thereby narrowing down the sequences for study. Generally, CNVs are described as differences in the number of gene copies present among individuals.

Typically, genes appear in pairs—one from each chromosome (i.e., diploid). Nonetheless, the number of gene copies can fluctuate due to CNVs. It’s estimated that CNVs account for about 5–10 percent of the human genome. The addition or deletion of gene copies can lead to changes in protein expression, which may affect health. Although the implications of most CNVs remain unclear, they have been linked to rare genomic disorders as well as neurodevelopmental traits and diseases.

The Database of Genomic Variants maintains a comprehensive record of identified CNVs, currently housing over 980,000 variants from 75 different studies.

How Do CNVs Form?

CNVs can either be inherited from parents or arise de novo (newly created). The inheritance patterns are still under investigation and may differ across populations. De novo CNVs are not passed down from parents; rather, they emerge during meiosis or early embryogenesis. Various processes during gamete formation, such as non-allelic homologous recombination, may lead to deletions or duplications of chromosome segments. Similar alterations can occur during the mitotic divisions of early zygote and blastocyst cells post-fertilization.

Implications of Copy Number Variants

While some CNVs have been associated with diseases, many individuals who are otherwise healthy possess these variants within their chromosomes. CNVs can appear on any chromosome, including sex chromosomes. Non-inherited genetic conditions are often referred to as sporadic. Although the frequency of de novo CNVs is believed to be lower than that of point mutations (SNPs), CNVs can affect larger chromosome regions, potentially leading to more significant complications, including neuropsychiatric disorders. Furthermore, de novo CNVs may be transmitted to future generations, resulting in inherited copy number variants.

The research tools used to analyze CNVs are continually evolving, as scientists strive to enhance and standardize the study of these repetitive genetic components.