Abstrakti

Recombination is an essential part of meiosis as it facilitates novel combinations of homologous chromosomes, following their successive segregation in offspring. Founder population size, demographic changes (eg. population bottlenecks or rapid expansion) can lead to variation in recombination rates across different populations. Previous research has shown that using population-specific reference panels has a significant effect on downstream population genomic analysis like haplotype phasing, genotype imputation and association, especially in the context of population isolates. Here, we developed a high-resolution recombination rate mapping at 10kb and 50kb scale using high-coverage (20-30x) whole-genome sequencing (WGS) data of 55 family trios from Finland and compared it to recombination rates of non-Finnish Europeans (NFE). We then tested the downstream effects of the population-specific recombination rates in statistical phasing and genotype imputation in Finns as compared to the same analyses performed by using the NFE-based recombination rates. Finnish recombination rates have a moderately high correlation (Spearman rho =0.67-0.79) with non-Finnish Europeans, although on average (across all autosomal chromosomes), Finnish rates (2.268textpm0.4209 cM/Mb) are 12-14% lower than NFE (2.641textpm0.5032 cM/Mb). Population-specific effective population sizes were found to have no significant effect in haplotype phasing accuracy (switch error rates, SER"2 and average imputation concordance rates (with reference panels in phasing: rates were 97-98% for common, 92-96% for low frequency and 78-90% for rare variants) irrespective of the recombination map used. Similarly, we found no effect of population-specific (Finnish) recombination maps in phasing with comparable switch error rates (SER) across autosomes when compared to HapMap based maps. Our results suggest that downstream population genomic analyses like haplotype phasing and genotype imputation mostly depend on population-specific contexts like appropriate reference panels and their sample size, but not on population-specific recombination maps or effective population sizes. Currently, available HapMap recombination maps seem robust for population-specific phasing and imputation pipelines, even in the context of relatively isolated populations like Finland.Competing Interest StatementThe authors have declared no competing interest.
Alkuperäiskielimuu / ei tiedossa
LehtibioRxiv
DOI - pysyväislinkit
TilaJulkaistu - 2020
OKM-julkaisutyyppiB1 Kirjoitus tieteellisessä aikakauslehdessä

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