RT Journal Article
SR Electronic
T1 Whole genome view of the consequences of a population bottleneck using 2926 genome sequences from Finland and United Kingdom
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 063388
DO 10.1101/063388
A1 Himanshu Chheda
A1 Priit Palta
A1 Matti Pirinen
A1 Shane McCarthy
A1 Klaudia Walter
A1 Seppo Koskinen
A1 Veikko Salomaa
A1 Mark Daly
A1 Richard Durbin
A1 Aarno Palotie
A1 Tero Aittokallio
A1 Samuli Ripatti
A1 Sequencing Initiative Suomi (SISu) Project
YR 2016
UL http://biorxiv.org/content/early/2016/07/12/063388.abstract
AB 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.