MRC Human Genetics Unit
Medical Research Council Human Genetics Unit

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Rarity is Common: The Genetics of Shetland

Whole genome sequencing reveals high number of ultra-rare genetic variants, particularly in gene coding and regulatory regions: December 2019

Shetland scenery with sheep
Image credit: Jim Wilson

Population isolates are groups of individuals that are isolated by factors such as geographic, social or cultural barriers. Such populations have a relatively small number of ancestors, and so particular genetic variants carried by these ‘founders’ are often carried by many people in the populations today, even if they are not common elsewhere. This process is known as the founder effect and is magnified if the population remains isolated over the intervening time, such that the gene pool diverges further from neighbouring populations (known as genetic drift).

Isolated populations, such as those in Orkney and Shetland Islands in the north of Scotland, therefore provide a valuable window into the roles of rare genetic variation in human traits and diseases, as a result of their unusual and distinct histories.

Through the Scottish Genome Partnership, researchers from the University of Edinburgh have analysed whole genome sequence data from 500 people from Shetland, and compared these genomes to the mainland Scottish population.

As expected we find the imprint of Shetland population history in the Shetland genome, with strong evidence for founder effects and genetic drift. These influences have combined to endow the Shetland genome with thousands of ultra-rare genetic variants, not observed previously in other populations.

 

While I expected there to be an uplift in the frequency of otherwise rare variants in Shetland, I was surprised both by how many there were and that this effect was more pronounced in important functional regions of the genome including regulatory and protein-coding regions of genes. This suggests the potential for rapid divergence of gene expression patterns in population isolates.

Jim WilsonProfessor of Human Genetics, Usher Institute & MRC Human Genetics Unit

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