Variant

In humans, if the genomes of two individuals were compared, on average they would be between 99.8–99.9% similar. It is the remaining small variation that accounts for all the differences seen between individuals. Although this may seem a tiny fraction, when applied to the 3 billion letters that make up the human genome, the numbers are significant: 0.1% represents three million individual changes.

Some genomic variants are harmless and will have no impact on health, whereas others account for physical differences or predisposition to specific health conditions.

The size of the genomic variant is not reflective of the impact it will have, if any, on the individual. Large variants in the genome can have no effect, while smaller changes can.

Among all cases of achondroplasia, 99% are caused by a single base change in a particular gene that codes for a protein involved in the regulation of bone growth. This is an example of how a tiny change in a person’s genome can have a significant effect.

Conversely, studies have shown that large variants may have no effect at all on the individual.¹ One study reported an individual who had a 9 million base-pair region missing from chromosome 4 and seemed unaffected.² It should be noted, however, that the effect that any variant will have on an individual will depend on where in the genome it occurs.

• If the genomes of two individuals were compared they would be 99.8–99.9% similar. All variation occurs in the remaining 0.1–0.2%.
• Variant in our genome account not only for our physical traits, such as height, but can also impact on our health.
• The size of variants in the genome does not reflect the impact they will have on the individual.

For clinicians

• HEE Genomics Education Programme: Genomics 101: From Genes to Genome course

References:

¹ Nowakowska, B. ‘Clinical interpretation of copy number variants in the human genome‘. Journal of Applied Genetics 2017: volume 58, issue 4, pages 449-457. doi: 10.1007/s13353-017-0407-4

² Bateman MS, Mehta SG and others. ‘A de novo 4q34 interstitial deletion of at least 9.3 Mb with no discernible phenotypic effect‘. American Journal of Medical Genetics 2010: volume 152A, issue 7, pages 1764-9. doi: 10.1002/ajmg.a.33426