Coalescence computations for large samples drawn from populations of time-varying sizes

Polański, Andrzej; Szczęsna, Agnieszka; Garbulowski, Mateusz; Kimmel, Marek

doi:10.1371/journal.pone.0170701

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…For a model with exponential growth with rate constant r , we used the approximation provided in Polanski et al (2017): …”

Section: Methodsmentioning

confidence: 99%

“…Note that X:A and Y:A depend only on the ratio between mutation rates on different chromosomes, not the absolute mutation rate. For a bottleneck of depth f , starting g 1 generations before the present and ending at g 1 + g 2 generations before the present: For a model with exponential growth with rate constant r , we used the approximation provided in Polanski et al (2017): Unequal sex ratios were modeled by calculating the number of X and Y chromosomes per autosome, given fixed autosomal effective population size, using standard formulae as in Sayres et al (2014), and passing these into the equations above via the parameter h X or h Y .…”

Section: Methodsmentioning

confidence: 99%

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Sequence and structural diversity of mouse Y chromosomes

Morgan¹,

Villena²

2016

Preprint

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13Over the 180 million years since their origin, the sex chromosomes of mammals have evolved a gene repertoire highly 14 specialized for function in the male germline. The mouse Y chromosome is unique among mammalian Y chromosomes char-15 acterized to date in that it is large, gene-rich and euchromatic. Yet little is known about its diversity in natural populations. 16Here we take advantage of published whole-genome sequencing data to survey the diversity of sequence and copy number 17 of sex-linked genes in three subspecies of house mice. Copy number of genes on the repetitive long arm of both sex chro-18 mosomes is highly variable, but sequence diversity in non-repetitive regions is decreased relative to expectations based on 19 autosomes. We use simulations and theory to show that this reduction in sex-linked diversity is incompatible with neutral 20 demographic processes alone, but is consistent with recent positive selection on genes active during spermatogenesis. Our 21 results support the hypothesis that the mouse sex chromosomes are engaged in ongoing intragenomic conflict.

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“…For a model with exponential growth with rate constant r , we used the approximation provided in Polanski et al (2017): …”

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Sequence and structural diversity of mouse Y chromosomes

Morgan¹,

Villena²

2016

Preprint

View full text Add to dashboard Cite

show abstract

“…We also compared our estimates of sex chromosome diversity to predictions from coalescent theory (Pool and Nielsen 2007;Polanski et al 2017) for the four models considered above. For this analysis, we focused on the ratios X:A and Y:A, which are independent of autosomal effective population size.…”

Section: Reduction In Sex-linked Diversity Is Inconsistent With Simplmentioning

confidence: 99%

“…For a model with exponential growth with rate constant r, we used the approximation provided in Polanski et al (2017):…”

Section: Models Of Sex-chromosome Diversity Under Neutral Coalescentmentioning

confidence: 99%

Sequence and Structural Diversity of Mouse Y Chromosomes

Morgan

Villena

2017

Molecular Biology and Evolution

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Over the 180 My since their origin, the sex chromosomes of mammals have evolved a gene repertoire highly specialized for function in the male germline. The mouse Y chromosome is unique among mammalian Y chromosomes characterized to date in that it is large, gene-rich and euchromatic. Yet, little is known about its diversity in natural populations. Here, we take advantage of published whole-genome sequencing data to survey the diversity of sequence and copy number of sex-linked genes in three subspecies of house mice. Copy number of genes on the repetitive long arm of both sex chromosomes is highly variable, but sequence diversity in nonrepetitive regions is decreased relative to expectations based on autosomes. We use simulations and theory to show that this reduction in sex-linked diversity is incompatible with neutral demographic processes alone, but is consistent with recent positive selection on genes active during spermatogenesis. Our results support the hypothesis that the mouse sex chromosomes are engaged in ongoing intragenomic conflict.

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“…Let E [ T i ; n ] denote the expected time for the number of ancestral lines to go from i to i − 1 in the coalescence process for a sample of n current haplotypes, which depends on the population history model. Thus, g ( k, d ; n ) depends on mutation rate μ and expected coalescent time intervals E [ T k ; n ], which can be numerically computed [12] or approximated by Monte Carlo. …”

Section: Methodsmentioning

confidence: 99%

Why are rare variants hard to impute? Coalescent models reveal theoretical limits in existing algorithms

Zoellner

2020

Preprint

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Genotype imputation is an indispensable step in human genetic studies. Large reference panels with deeply sequenced genomes now allow interrogating variants with minor allele frequency < 1% without sequencing. While it is critical to consider limits of this approach, imputation methods for rare variants have only done so empirically; the theoretical basis of their imputation accuracy has not been explored. To provide theoretical consideration of imputation accuracy under the current imputation framework, we develop a coalescent model of imputing rare variants, leveraging the joint genealogy of the sample to be imputed and reference individuals. We show that broadly used imputation algorithms includes model miss-specifications about this joint genealogy that limit the ability to correctly impute rare variants. We develop closed-form solutions for the probability distribution of this joint genealogy and quantify the inevitable error rate resulting from the model miss-specification across a range of allele frequencies and reference sample sizes. We show that the probability of a falsely imputed minor allele decreases with reference sample size, but the proportion of falsely imputed minor alleles mostly depends on the allele count in the reference sample. We summarize the impact of this error on genotype imputation on association tests by calculating the r2 between imputed and true genotype and show that even when modeling other sources of error, the impact of the model miss-specification have a significant impact on the r2 of rare variants. These results provide a framework for developing new imputation algorithms and for interpreting rare variant association analyses.

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Coalescence computations for large samples drawn from populations of time-varying sizes

Cited by 8 publications

References 39 publications

Sequence and structural diversity of mouse Y chromosomes

Sequence and structural diversity of mouse Y chromosomes

Sequence and Structural Diversity of Mouse Y Chromosomes

Why are rare variants hard to impute? Coalescent models reveal theoretical limits in existing algorithms

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