What are copy number variants?
The comparative study of different genomes in the Human Genome Project in 2001 revealed a surprising level of variability between individuals. The findings revealed that around 5% of the human genome consists of redundant DNA segments present multiple times in various locations across the entire human genome. These genomic regions became known as interspersed segmental duplications and their existence proved for the first time, that certain areas of the genome had changed in copy number during human evolution1. These genomic areas are now recognized as being highly susceptible to copy number variation and are frequently studied in relation to human disease.
Copy number variation contributes to population level genetic differences, and along with translocations and inversions, are responsible for causing structural alterations within the human genome. Genetic alterations can range in size, with the most common source of variation involving only single base pair (bp) alterations, however larger scale alterations may involve chromosomal rearrangements.
The term copy number variants refers to intermediate-large scale genomic alterations, which are operationally defined as DNA segments larger than 1,000 base pairs but typically less than 5 megabases, equivalent to the cytogenetic level of resolution2.
Copy number variants (CNVs) can range in size and composition and often involve insertion and deletion events affecting 1 kB-5 Mb genomic regions, because of the length of the genome that they can alter, they are considered an intermediate-large scale source of variation.
CNVs can be classified into two subtypes: copy number polymorphisms (CNPs) or micro-insertions and micro-deletions, dependent on the size of the genome that has been affected. CNPs are smaller and typically span 1-10 kB in length and have been associated with genes encoding for drug detoxification and immunity proteins. Whereas micro-insertions and deletions affect much larger areas of the genome and can be over 1 million bp in length. Micro-insertions and deletion events have been linked with such as neuro-cognitive health conditions including autism and schizophrenia2.
The BRCA genes are not the only cancer risk genes; there are now over 100 variants recognized to enhance the risk of developing Each year the National Genomic Test (NGT) Directory UK is updated to include all new genes that should be targeted through genomic testing services commissioned by the NHS for cancer diagnosis and treatment management. Recent updates to the NGT directory have seen the addition of 5 new genes: REST, DLST, SLC25A11, RNF43 and MDH2, which have an association to inherited cancer syndromes. Often, it is the combination as well as the frequency of variants that contribute to the increase in cancer risk.