Cargando…

Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA

Genetic disease burden in ancient communities has barely been evaluated despite an ever expanding body of ancient genomes becoming available. In this study, we inspect 2729 publicly available ancient genomes (100 BP—52000 BP) for the presence of pathogenic variants in 32643 disease-associated loci....

Descripción completa

Detalles Bibliográficos
Autores principales: Toncheva, Draga, Marinova, Maria, Borovska, Plamenka, Serbezov, Dimitar
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231702/
https://www.ncbi.nlm.nih.gov/pubmed/35749392
http://dx.doi.org/10.1371/journal.pone.0269628
_version_ 1784735402314170368
author Toncheva, Draga
Marinova, Maria
Borovska, Plamenka
Serbezov, Dimitar
author_facet Toncheva, Draga
Marinova, Maria
Borovska, Plamenka
Serbezov, Dimitar
author_sort Toncheva, Draga
collection PubMed
description Genetic disease burden in ancient communities has barely been evaluated despite an ever expanding body of ancient genomes becoming available. In this study, we inspect 2729 publicly available ancient genomes (100 BP—52000 BP) for the presence of pathogenic variants in 32643 disease-associated loci. We base our subsequent analyses on 19 variants in seven genes—PAH, EDAR, F11, HBB, LRRK2, SLC12A6 and MAOA, associated with monogenic diseases and with well-established pathogenic impact in contemporary populations. We determine 230 homozygote genotypes of these variants in the screened 2729 ancient DNA samples. Eleven of these are in the PAH gene (126 ancient samples in total), a gene associated with the condition phenylketonuria in modern populations. The variants examined seem to show varying dynamics over the last 10000 years, some exhibiting a single upsurge in frequency and subsequently disappearing, while others maintain high frequency levels (compared to contemporary population frequencies) over long time periods. The geographic distribution and age of the ancient DNA samples with established pathogenic variants suggests multiple independent origin of these variants. Comparison of estimates of the geographic prevalence of these variants from ancient and contemporary data show discontinuity in their prevalence and supports their recurrent emergence. The oldest samples in which a variant is established might give an indication of their age and place origin, and an EDAR gene pathogenic variant was established in a sample estimated to be 33210–32480 calBCE. Knowledge about the historical prevalence of variants causing monogenic disorders provides insight on their emergence, dynamics and spread.
format Online
Article
Text
id pubmed-9231702
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-92317022022-06-25 Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA Toncheva, Draga Marinova, Maria Borovska, Plamenka Serbezov, Dimitar PLoS One Research Article Genetic disease burden in ancient communities has barely been evaluated despite an ever expanding body of ancient genomes becoming available. In this study, we inspect 2729 publicly available ancient genomes (100 BP—52000 BP) for the presence of pathogenic variants in 32643 disease-associated loci. We base our subsequent analyses on 19 variants in seven genes—PAH, EDAR, F11, HBB, LRRK2, SLC12A6 and MAOA, associated with monogenic diseases and with well-established pathogenic impact in contemporary populations. We determine 230 homozygote genotypes of these variants in the screened 2729 ancient DNA samples. Eleven of these are in the PAH gene (126 ancient samples in total), a gene associated with the condition phenylketonuria in modern populations. The variants examined seem to show varying dynamics over the last 10000 years, some exhibiting a single upsurge in frequency and subsequently disappearing, while others maintain high frequency levels (compared to contemporary population frequencies) over long time periods. The geographic distribution and age of the ancient DNA samples with established pathogenic variants suggests multiple independent origin of these variants. Comparison of estimates of the geographic prevalence of these variants from ancient and contemporary data show discontinuity in their prevalence and supports their recurrent emergence. The oldest samples in which a variant is established might give an indication of their age and place origin, and an EDAR gene pathogenic variant was established in a sample estimated to be 33210–32480 calBCE. Knowledge about the historical prevalence of variants causing monogenic disorders provides insight on their emergence, dynamics and spread. Public Library of Science 2022-06-24 /pmc/articles/PMC9231702/ /pubmed/35749392 http://dx.doi.org/10.1371/journal.pone.0269628 Text en © 2022 Toncheva et al 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 use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Toncheva, Draga
Marinova, Maria
Borovska, Plamenka
Serbezov, Dimitar
Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA
title Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA
title_full Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA
title_fullStr Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA
title_full_unstemmed Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA
title_short Spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient DNA
title_sort spatio-temporal dynamics of pathogenic variants associated with monogenic disorders reconstructed with ancient dna
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9231702/
https://www.ncbi.nlm.nih.gov/pubmed/35749392
http://dx.doi.org/10.1371/journal.pone.0269628
work_keys_str_mv AT tonchevadraga spatiotemporaldynamicsofpathogenicvariantsassociatedwithmonogenicdisordersreconstructedwithancientdna
AT marinovamaria spatiotemporaldynamicsofpathogenicvariantsassociatedwithmonogenicdisordersreconstructedwithancientdna
AT borovskaplamenka spatiotemporaldynamicsofpathogenicvariantsassociatedwithmonogenicdisordersreconstructedwithancientdna
AT serbezovdimitar spatiotemporaldynamicsofpathogenicvariantsassociatedwithmonogenicdisordersreconstructedwithancientdna