Whole-genome view of the consequences of a population bottleneck using 2926 genome sequences from Finland and United Kingdom
Year: 2017
Type: article
Study design: Observational Study
Abstract: Isolated populations with enrichment of variants due to recent population bottlenecks provide a powerful resource for identifying disease-associated genetic variants and genes. As a model of an isolate population, we sequenced the genomes of 1463 Finnish individuals as part of the Sequencing Initiative Suomi (SISu) Project. We compared the genomic profiles of the 1463 Finns to a sample of 1463 British individuals that were sequenced in parallel as part of the UK10K Project. Whereas there were no major differences in the allele frequency of common variants, a significant depletion of variants in the rare frequency spectrum was observed in Finns when comparing the two populations. On the other hand, we observed >2.1 million variants that were twice as frequent among Finns compared to Britons and 800,000 variants that were more than 10 times more frequent in Finns. Furthermore, in Finns we observed a relative proportional enrichment of variants in the minor allele frequency range between 2 - 5% (p < 2.2×10 −16 ). When stratified by their functional annotations, loss-of-function (LoF) variants showed the highest proportional enrichment in Finns (p = 0.0291). In the noncoding part of the genome, variants in conserved regions (p = 0.002) and promoters (p = 0.01) were also significantly enriched in the Finnish samples. These functional categories represent the highest a priori power for downstream association studies of rare variants using population isolates.
Authors: for the Sequencing Initiative Suomi (SISu) Project, Himanshu Chheda, Priit Palta, Matti Pirinen, Shane McCarthy, Klaudia Walter, Seppo Koskinen, Veikko Salomaa, Mark Daly, Richard Durbin, Aarno Palotie, Tero Aittokallio, Samuli Ripatti
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $2,790
Awards: G1025295093, G1332667197, G1426619399, G1520690021, G209825041, G2919493513, G3216122662, G3401497200, G3701006503, G3728971702, G3942382998, G4330096051, G4498320881, G4612446324, The Avon Longitudinal Study of Parents and Children: An international resource for population
genomics and lifecourse epidemiology. Core Programme Support 2011-2015 and Core programme support 2014-2019, G4855546878, G5435746767, G5943355715, G6030094504, G616188461, G6229538190, G7221506883, G7650667963, G77874731, G8154434148, G8311891658, G841744108, G8653388093, Wellcome Trust Sanger Institute - generic account for deposition of all core- funded research papers
OpenAlex ID: W2583931623