Rare genetic variants unexpectedly common in humans

Rare genetic variants - those carried by fewer than five in 1,000 people - are much more common than previously thought, according to two studies published in Science.

The research teams also found that most human genetic variants are 'rare', and that many have an impact on the function of the proteins they encode. The prevalence of these mutations could make identification of the genetic roots of common diseases more difficult than expected.

'Our results suggest there are many, many places in the genome where one individual, or a few individuals, have something different', said Dr John Novembre, an assistant professor of evolutionary biology at University of California Los Angeles (UCLA), and senior author of one of the studies. 'I knew there would be rare variation but had no idea there would be so much of it. Overall, it is surprisingly common that there is a rare variant in the population'.

The two studies sequenced all the exon — the parts of the genes that code for proteins — in the genomes of over 16,000 people, looking for single letter changes in the DNA. Due to the rarity of these single nucleotide variants (SNVs), some would only be found in a single person.

In fact, 74 percent of the variants discovered in the UCLA study were carried by only one or two people, and 95 percent of the total variants proved to be rare. In the other, University of Washington-based study, 86 percent of all variants were rare, as defined by them being present in fewer than five people in 1,000. More importantly, these rare variants were much more likely to have medical or biological consequences than the common variants targeted in most genetic studies.

The abundance of the rare gene variants can be explained by the population explosion that started some 5,000 years ago. As these new variants have emerged relatively recently, they have not been subject to natural selection for long enough for disadvantageous mutations to be removed from the population.

Other scientists were less surprised by the plentitude of rare variants. 'Lots of new variants are no surprise', tweeted Leonid Kruglyad, professor of genomics and evolutionary biology at Princeton University. According to Professor Kruglyad, the number of newly discovered variants grows as more and more people's genomes are sequenced. However, the two studies did find more rare variants than predicted, which he says is 'a signature of population growth'.