Copy number variation

Copy number variation (CNV) is a phenomenon in genetics where the number of copies of a particular gene varies from one individual to the next within a population. CNVs can encompass a range of genetic material alterations from deletions, duplications, and in some cases, complex multi-allelic variations. These variations can influence gene expression levels and are a significant source of genetic diversity among individuals. They have been implicated in various human diseases as well as in the response to environmental factors and susceptibility to infections.

Overview

Copy number variations are segments of DNA that are 1 kilobase (kb) or larger and are present at a variable copy number in comparison with a reference genome. The concept of CNV is distinct from Single nucleotide polymorphisms (SNPs), which involve variation at a single base pair. CNVs can affect gene dosage, gene structure, and gene expression, potentially leading to phenotypic variations and alterations in disease susceptibility.

Mechanisms of CNV Formation

CNVs can arise through several mechanisms, including but not limited to:

• Non-allelic homologous recombination (NAHR)
• Fork stalling and template switching (FoSTeS)
• Microhomology-mediated break-induced replication (MMBIR)
• Non-homologous end joining (NHEJ)

These mechanisms often involve errors during DNA replication or repair, leading to the duplication or deletion of segments of the genome.

Clinical Significance

Copy number variations have been associated with a wide range of genetic disorders and conditions. For example, duplications or deletions in specific regions of the genome can lead to developmental disorders such as DiGeorge syndrome and Williams syndrome. CNVs are also implicated in neuropsychiatric disorders, including schizophrenia and autism spectrum disorders (ASD).

In addition to their role in disease, CNVs are also considered in the context of genetic diversity and evolution. They can confer adaptive advantages or disadvantages, influencing an individual's fitness and susceptibility to diseases.

Detection Methods

Several techniques are used to detect CNVs, including:

• Array comparative genomic hybridization (aCGH)
• Single nucleotide polymorphism array (SNP array)
• Next-generation sequencing (NGS)
• Quantitative PCR (qPCR)

Each method has its advantages and limitations in terms of resolution, cost, and throughput.

Research and Future Directions

Research into CNVs continues to uncover their roles in health and disease. Efforts are underway to better understand the mechanisms underlying CNV formation, their functional impacts, and their contributions to genetic diversity and evolution. Additionally, the integration of CNV analysis into clinical practice is an area of ongoing development, with the potential to improve diagnostic accuracy and personalized medicine approaches.

See Also

• Genetic variation
• Structural variation (genetics)
• Human genome