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Whole-genome view of the consequences of a population bottleneck using 2926 genome sequences from Finland and United Kingdom.

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 with 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 and 5% (P<2.2 × 10^-16). When stratified by their functional annotations, loss-of-function variants showed the highest proportional enrichment in Finns (P=0.0291). In the non-coding 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.

SUBMITTER: Chheda H

PROVIDER: S-EPMC5346294 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe response to the COVID-19 pandemic in the United Kingdom included large scale changes to healthcare delivery, without fully understanding the potential for unexpected effects caused by these changes. The aim was "to ascertain the characteristics of patients, uncertainty over diagnosis, or features of the emergency response to the pandemic that could be modified to mitigate against future excess deaths".MethodsReview of the entire pathway of care of patients whose death was registered in Salford during the 8 week period of the first wave (primary care, secondary care, 111 and 999 calls) in order to create a single record of healthcare prior to death. An expert panel judged avoidability of death against the National Mortality Case Record Review Programme scale. The panel identified themes using a structured judgement review format.ResultsThere were 522 deaths including 197 in hospital, and 190 in care homes. 51% of patients were female, 81% Caucasian, age 79 ± 9 years. Dementia was present in 35%, COVID-19 was cause of death in 44%. Healthcare contact prior to death was most frequently with primary care (81% of patients). Forty-six patients (9%) had healthcare appointments cancelled (median 1 cancellation, range 1-9). Fewer than half of NHS 111 calls were answered during this period. 18% of deaths contained themes consistent with some degree of avoidability. In people aged ≥75 years who lived at home this was 53%, in care home residents 29% and in patients with learning disability 44% (n = 9). Common themes were; delays in patients presenting to care providers (10%), delays in testing (17%), avoidable exposure to COVID-19 (26%), delays in provider response (5%), and sub-optimal care (11%). For avoidability scores of 2 or 3 (indicating more than 50% chance of avoidability), 44% of cases had > 2 themes.ConclusionsThe initial emergency response had unforeseen consequences resulting in late presentation, sub-optimal assessments, and delays in receiving care. Death in more vulnerable groups was more likely to display avoidability themes.

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Whole-genome view of the consequences of a population bottleneck using 2926 genome sequences from Finland and United Kingdom.

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