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Recurrent mutation in the ancestry of a rare variant

Recurrent mutation produces multiple copies of the same allele which may be co-segregating in a population. Yet, most analyses of allele-frequency or site-frequency spectra assume that all observed copies of an allele trace back to a single mutation. We develop a sampling theory for the number of la...

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Autores principales: Wakeley, John, Fan, Wai-Tong (Louis), Koch, Evan, Sunyaev, Shamil
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324944/
https://www.ncbi.nlm.nih.gov/pubmed/36967220
http://dx.doi.org/10.1093/genetics/iyad049
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author Wakeley, John
Fan, Wai-Tong (Louis)
Koch, Evan
Sunyaev, Shamil
author_facet Wakeley, John
Fan, Wai-Tong (Louis)
Koch, Evan
Sunyaev, Shamil
author_sort Wakeley, John
collection PubMed
description Recurrent mutation produces multiple copies of the same allele which may be co-segregating in a population. Yet, most analyses of allele-frequency or site-frequency spectra assume that all observed copies of an allele trace back to a single mutation. We develop a sampling theory for the number of latent mutations in the ancestry of a rare variant, specifically a variant observed in relatively small count in a large sample. Our results follow from the statistical independence of low-count mutations, which we show to hold for the standard neutral coalescent or diffusion model of population genetics as well as for more general coalescent trees. For populations of constant size, these counts are distributed like the number of alleles in the Ewens sampling formula. We develop a Poisson sampling model for populations of varying size and illustrate it using new results for site-frequency spectra in an exponentially growing population. We apply our model to a large data set of human SNPs and use it to explain dramatic differences in site-frequency spectra across the range of mutation rates in the human genome.
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spelling pubmed-103249442023-07-07 Recurrent mutation in the ancestry of a rare variant Wakeley, John Fan, Wai-Tong (Louis) Koch, Evan Sunyaev, Shamil Genetics Investigation Recurrent mutation produces multiple copies of the same allele which may be co-segregating in a population. Yet, most analyses of allele-frequency or site-frequency spectra assume that all observed copies of an allele trace back to a single mutation. We develop a sampling theory for the number of latent mutations in the ancestry of a rare variant, specifically a variant observed in relatively small count in a large sample. Our results follow from the statistical independence of low-count mutations, which we show to hold for the standard neutral coalescent or diffusion model of population genetics as well as for more general coalescent trees. For populations of constant size, these counts are distributed like the number of alleles in the Ewens sampling formula. We develop a Poisson sampling model for populations of varying size and illustrate it using new results for site-frequency spectra in an exponentially growing population. We apply our model to a large data set of human SNPs and use it to explain dramatic differences in site-frequency spectra across the range of mutation rates in the human genome. Oxford University Press 2023-03-27 /pmc/articles/PMC10324944/ /pubmed/36967220 http://dx.doi.org/10.1093/genetics/iyad049 Text en © The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Investigation
Wakeley, John
Fan, Wai-Tong (Louis)
Koch, Evan
Sunyaev, Shamil
Recurrent mutation in the ancestry of a rare variant
title Recurrent mutation in the ancestry of a rare variant
title_full Recurrent mutation in the ancestry of a rare variant
title_fullStr Recurrent mutation in the ancestry of a rare variant
title_full_unstemmed Recurrent mutation in the ancestry of a rare variant
title_short Recurrent mutation in the ancestry of a rare variant
title_sort recurrent mutation in the ancestry of a rare variant
topic Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10324944/
https://www.ncbi.nlm.nih.gov/pubmed/36967220
http://dx.doi.org/10.1093/genetics/iyad049
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