Copy number imbalance
Almost every cell in our bodies contains DNA packaged into chromosomes that contain all the information required for the functioning of that cell and collectively for the human body as a whole.
The approximately 3 billion DNA basepairs in the human genome are packaged into 23 pairs of chromosomes in total, plus some mitochondrial DNA. 22 of the 23 pairs are autosomal chromosomes, the remaining pair are sex-determining, XX for female and XY for male.
The vast majority of the DNA we all have is identical; however we all have differences in our DNA that make us individuals. These differences can range from single base pair changes to gains or losses of millions of base pairs. Larger gains or losses, compared to our two normal two copies of DNA, are termed copy number imbalance.
Copy number imbalance can be inherited (or occur early in development) and can be present in every cell of the body. Copy number imbalances are usually benign but occasionally they can lead to serious disorders. Conditions that manifest as intellectual disability, such as developmental delay and mental retardation sometimes result from the presence of a copy number imbalance in an individual’s genome. Clinical geneticists may employ techniques to examine the genome copy number to assist in the diagnosis of certain disorders.
Copy number imbalance can also occur through a de novo (not inherited from a parent) mutation in a subset of cells, such as occurs in cancer. Cancer cells can often be diagnosed through having very abnormal looking chromosomes with regions of the genome that contain genes critical for the regulation of a cells growth being amplified (large gain of DNA copies), for example genes such as MYC and HER2 gene amplification in cancer. Equally genes important in cancer can also be found to be deleted.
Another area of interest where copy number imbalance has come to importance is the field of IVF. The majority of human eggs cultured by IVF have abnormal numbers of chromosomes (aneuploidy), particularly so as potential mothers going through IVF reach their late thirties. The screening of human eggs for the correct number of chromosomes (euploid) prior to implantation is hoped to improve pregnancy rates in an IVF cycle.
Copy number imbalance can be detected using traditional cytogenetic techniques such as, chromosome banding, fluorescent in situ hybridization (FISH) and comparative genomic hybridization. Over the last 10 years or so it has become more common to use microarrays to assess copy number imbalance across a whole genome using a technique known as arrayCGH.