Copy number variants

Although the mechanism is not fully understood, one theory is that during the complicated process of replication, chromosome sections can be either lost or duplicated due to unequal crossing over between homologous repetitive regions of DNA. This phenomenon is known as non-allelic homologous recombination.

The different types of CNV that can occur are:

• deletions and microdeletions: when sections of the genome have been deleted, resulting in loss of genetic material (see Figure 1); and
• duplications and microduplications: when sections of the genome have been duplicated, resulting in a gain of genetic material.

Figure 1: Deletions and microdeletions result in loss of genetic material

CNVs are the second most common type of genomic variation, after structural number variants. They result in too much or too little protein being produced, which in turn can influence gene expression and/or contribute to disease.

Tumour cells often have structural variants that result in CNVs.

One of the most well-known examples of a disease-causing CNV is Huntingdon’s disease, which is caused by a repeating sequence of three base pairs (known as a trinucleotide repeat) at the end of the coding region of the HTT gene; people with 40 or more repeats are affected by Huntington’s disease.

CNVs at many recurrent genome hotspots are also associated with epilepsy.

• CNVs are regions of our genome that vary in the number of copies present, due to either duplication or deletion.
• CNVs are classed as structural changes, and recent scientific research suggests that they may account for up to 9.5% of the human genome.
• As well as contributing to normal genomic variation, CNVs can also contribute to disease or influence gene expression.

For clinicians

• Genetic Alliance UK: Chromosomal disorders 
• NHS England Genomics Education Programme: What are copy number variants? 

References: 

• Zarrei M, MacDonald JR, Merico D and others. ‘A copy number variation map of the human genome‘. Nature Reviews Genetics 2015: volume 16, pages 172–183. DOI: 10.1038/nrg3871 

For patients

• Unique: Understanding Rare Chromosome and Gene Disorders. Deletions and microdeletions (PDF, two pages)
• Unique: Understanding Rare Chromosome and Gene Disorders. Duplications and microduplications (PDF, two pages)