Population Genomic Analyses of DNA from Ancient Remains

Jakobsson, Torsten Günther and Mattias

doi:10.1002/9781119487845.ch10

Cited by 4 publications

(2 citation statements)

References 127 publications

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“…As a result, most ancient genomes have low breadth and depth of coverage, hindering confident genotype calling. Instead, pseudo-haploid data are commonly generated by sampling one allele per variant site 3,4 . Evermore methods and tools are developed to study population structure, including diploid genetic properties…”

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confidence: 99%

Imputation of ancient human genomes

et al. 2023

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Due to postmortem DNA degradation and microbial colonization, most ancient genomes have low depth of coverage, hindering genotype calling. Genotype imputation can improve genotyping accuracy for low-coverage genomes. However, it is unknown how accurate ancient DNA imputation is and whether imputation introduces bias to downstream analyses. Here we re-sequence an ancient trio (mother, father, son) and downsample and impute a total of 43 ancient genomes, including 42 high-coverage (above 10x) genomes. We assess imputation accuracy across ancestries, time, depth of coverage, and sequencing technology. We find that ancient and modern DNA imputation accuracies are comparable. When downsampled at 1x, 36 of the 42 genomes are imputed with low error rates (below 5%) while African genomes have higher error rates. We validate imputation and phasing results using the ancient trio data and an orthogonal approach based on Mendel’s rules of inheritance. We further compare the downstream analysis results between imputed and high-coverage genomes, notably principal component analysis, genetic clustering, and runs of homozygosity, observing similar results starting from 0.5x coverage, except for the African genomes. These results suggest that, for most populations and depths of coverage as low as 0.5x, imputation is a reliable method that can improve ancient DNA studies.

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confidence: 99%

Imputation of ancient human genomes

et al. 2023

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“…Analyses of ancient dog and wolf genomes have advanced our understanding of their evolutionary history ( Thalmann et al 2013 ; Skoglund et al 2015 ; Frantz et al 2016 ; Botigué et al 2017 ; Ní Leathlobhair et al 2018 ; Ollivier et al 2018 ; Bergström et al 2020 , 2022 ; Loog et al 2020 ; Sinding et al 2020 , 2020 ; Da Silva Coelho et al 2021 ; Feuerborn et al 2021 ; Ramos-Madrigal et al 2021 ). However, these insights have been limited by the typically low coverage and degraded nature of ancient DNA (aDNA), which leads to elevated uncertainty in genotype calling and restricts the type of questions that can be confidently addressed ( Axelsson et al 2008 ; Dabney et al 2013 b ; Günther and Jakobsson 2019 ; Günther and Nettelblad 2019 ). Common approaches to dealing with low-coverage aDNA data include ‘pseudohaploidisation’—the random sampling of an allele at a given site, and genotype likelihoods, which incorporate genotype uncertainty due to read-depth and base quality.…”

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confidence: 99%

Imputation of ancient canid genomes reveals inbreeding history over the past 10,000 years

Bougiouri,

Aninta,

Charlton

et al. 2024

Preprint

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The multi-millenia long history between dogs and humans has justly placed them at the forefront of archeological and genomic research. Despite ongoing efforts including the analysis of ancient dog and wolf genomes, many questions remain regarding their geographic and temporal origins, and the microevolutionary processes that led to the huge diversity of breeds today. Although ancient genomes provide valuable information, their use is significantly hindered by low depth of coverage and post-mortem damage, which often inhibits confident genotype calling. In the present study, we assess how genotype imputation of ancient dog and wolf genomes, utilising a large reference panel, can improve the resolution afforded by ancient genomic datasets. Imputation accuracy was evaluated by down-sampling 10 high coverage ancient and modern dog and wolf genomes to 0.05-2x coverage and comparing concordance between imputed and high coverage genotypes. We also measured the impact of imputation on principal component analyses (PCA) and runs of homozygosity (ROH). Our findings show high (R2 > 0.9) imputation accuracy for dogs with coverage as low as 0.5x and for wolves as low as 1.0x. We then imputed a worldwide dataset of 81 published ancient dog and wolf genomes, in addition to nine newly sequenced medieval and early modern period European dogs, to assess changes in inbreeding during the last 10,000 years of dog evolution. Ancient dog and wolf populations generally exhibited lower inbreeding levels than present-day individuals, though with some exceptions occurring in ancient Arctic and European dogs. Interestingly, regions with low ROH density maintained across ancient and present-day samples were significantly associated with genes related to olfaction and immune response. Our study indicates that imputing ancient canine genomes is a viable strategy that allows for the use of analytical methods previously limited to high-quality genetic data.

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An empirical evaluation of genotype imputation of ancient DNA

Xue

Sun

et al. 2021

Preprint

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Genome-wide association study (GWAS) is fundamentally designed to detect disease-causing genes. To reduce spurious associations or improve statistical power, about 80% of GWASs arbitrarily adjusted for demographic and clinical covariates. However, adjustment strategies in GWASs have not achieved consistent conclusions. Given the initial aim of GWAS that is to identify the causal association between a specific causal single-nucleotide polymorphism (SNP) and disease trait, we summarized all complex relationships of the target SNP, covariate and disease trait into 15 causal diagrams according to various roles of the covariate. Following each causal diagram, we conducted a series of theoretical justifications and statistical simulations. Our results demonstrate that it is unadvisable to adjust for any demographic or clinical covariates. We illustrate our point by applying GWASs for body mass index (BMI) and breast cancer, including adjusting and non-adjusting for age and smoking status. Genetic effects and P values might vary across different strategies. Instead, adjustments for SNPs (G') should be strongly recommended when G' are in linkage disequilibrium with the target SNP, and correlated with disease trait conditional on the target SNP. Specifically, adjustment for such G' can block all the confounding paths between the target SNP and disease trait, and avoid over-adjusting for colliders or intermediaries.

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Population Genomic Analyses of DNA from Ancient Remains

Cited by 4 publications

References 127 publications

Imputation of ancient human genomes

Imputation of ancient human genomes

Imputation of ancient canid genomes reveals inbreeding history over the past 10,000 years

An empirical evaluation of genotype imputation of ancient DNA

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