CNVs: a universe of variations

Defning CNVs

Dark bue chromosomes with copy number variations / insversions

Genetic variants of the human genome can differ very much in size. From the smallest ones (variants affecting on single nucleotide: Single Nucleotide Variations – SNVs) to the largest ones (variants affecting the shape and number of an entire chromosome), everything can stay in the middle. Variants comprised between 1,000 bp (1Kb) and 1,000,000 bp (1Mb) are usually referred to as Structural Variations or Structural Variants (SVs). SVs may be consistent with different localization or orientation of the relevant DNA tract or with alteration of the number of copies (Copy Number Variations – CNVs). According to the definition of SVs, several authors refer to CNVs as variations between 1Kb and 1Mb, although the concept of CNV remains very flexible, with some colleagues using it also to describe larger dosage variations at the submicroscopic or chromosomal level.

Bening and pathogenic

CNVs lead to gain or loss of genomic material and may be caused by deletions, duplications, multiplications or insertions.  As such, CNVs may include (part of) one or more genes, with or without clinical consequences such as complex syndromes, disease susceptibility and drug response. CNVs may be acquired or de novo. They are a constitutive part of the human genomic architecture and have been found also in several other mammals, playing a fundamental role in interindividual variability and evolution.

Allele frequencies and allele numbers

Some CNVs are very frequent, showing an allele frequency of more than 1%. Of course such frequent CNVs are not pathogenic and are referred to as CNPs (Copy Number Polymorphisms).  At certain genomic loci, some CNVs can show several different alleles. Such CNVs are also called multi-allelic CNVs or mCNVs.

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