Cargando…

Population history modulates the fitness effects of Copy Number Variation in the Roma

We provide the first whole genome Copy Number Variant (CNV) study addressing Roma, along with reference populations from South Asia, the Middle East and Europe. Using CNV calling software for short-read sequence data, we identified 3171 deletions and 489 duplications. Taking into account the known p...

Descripción completa

Detalles Bibliográficos
Autores principales: Antinucci, Marco, Comas, David, Calafell, Francesc
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449987/
https://www.ncbi.nlm.nih.gov/pubmed/37311904
http://dx.doi.org/10.1007/s00439-023-02579-5
_version_ 1785095090957451264
author Antinucci, Marco
Comas, David
Calafell, Francesc
author_facet Antinucci, Marco
Comas, David
Calafell, Francesc
author_sort Antinucci, Marco
collection PubMed
description We provide the first whole genome Copy Number Variant (CNV) study addressing Roma, along with reference populations from South Asia, the Middle East and Europe. Using CNV calling software for short-read sequence data, we identified 3171 deletions and 489 duplications. Taking into account the known population history of the Roma, as inferred from whole genome nucleotide variation, we could discern how this history has shaped CNV variation. As expected, patterns of deletion variation, but not duplication, in the Roma followed those obtained from single nucleotide polymorphisms (SNPs). Reduced effective population size resulting in slightly relaxed natural selection may explain our observation of an increase in intronic (but not exonic) deletions within Loss of Function (LoF)-intolerant genes. Over-representation analysis for LoF-intolerant gene sets hosting intronic deletions highlights a substantial accumulation of shared biological processes in Roma, intriguingly related to signaling, nervous system and development features, which may be related to the known profile of private disease in the population. Finally, we show the link between deletions and known trait-related SNPs reported in the genome-wide association study (GWAS) catalog, which exhibited even frequency distributions among the studied populations. This suggests that, in general human populations, the strong association between deletions and SNPs associated to biomedical conditions and traits could be widespread across continental populations, reflecting a common background of potentially disease/trait-related CNVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00439-023-02579-5.
format Online
Article
Text
id pubmed-10449987
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher Springer Berlin Heidelberg
record_format MEDLINE/PubMed
spelling pubmed-104499872023-08-26 Population history modulates the fitness effects of Copy Number Variation in the Roma Antinucci, Marco Comas, David Calafell, Francesc Hum Genet Original Investigation We provide the first whole genome Copy Number Variant (CNV) study addressing Roma, along with reference populations from South Asia, the Middle East and Europe. Using CNV calling software for short-read sequence data, we identified 3171 deletions and 489 duplications. Taking into account the known population history of the Roma, as inferred from whole genome nucleotide variation, we could discern how this history has shaped CNV variation. As expected, patterns of deletion variation, but not duplication, in the Roma followed those obtained from single nucleotide polymorphisms (SNPs). Reduced effective population size resulting in slightly relaxed natural selection may explain our observation of an increase in intronic (but not exonic) deletions within Loss of Function (LoF)-intolerant genes. Over-representation analysis for LoF-intolerant gene sets hosting intronic deletions highlights a substantial accumulation of shared biological processes in Roma, intriguingly related to signaling, nervous system and development features, which may be related to the known profile of private disease in the population. Finally, we show the link between deletions and known trait-related SNPs reported in the genome-wide association study (GWAS) catalog, which exhibited even frequency distributions among the studied populations. This suggests that, in general human populations, the strong association between deletions and SNPs associated to biomedical conditions and traits could be widespread across continental populations, reflecting a common background of potentially disease/trait-related CNVs. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00439-023-02579-5. Springer Berlin Heidelberg 2023-06-14 2023 /pmc/articles/PMC10449987/ /pubmed/37311904 http://dx.doi.org/10.1007/s00439-023-02579-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Investigation
Antinucci, Marco
Comas, David
Calafell, Francesc
Population history modulates the fitness effects of Copy Number Variation in the Roma
title Population history modulates the fitness effects of Copy Number Variation in the Roma
title_full Population history modulates the fitness effects of Copy Number Variation in the Roma
title_fullStr Population history modulates the fitness effects of Copy Number Variation in the Roma
title_full_unstemmed Population history modulates the fitness effects of Copy Number Variation in the Roma
title_short Population history modulates the fitness effects of Copy Number Variation in the Roma
title_sort population history modulates the fitness effects of copy number variation in the roma
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449987/
https://www.ncbi.nlm.nih.gov/pubmed/37311904
http://dx.doi.org/10.1007/s00439-023-02579-5
work_keys_str_mv AT antinuccimarco populationhistorymodulatesthefitnesseffectsofcopynumbervariationintheroma
AT comasdavid populationhistorymodulatesthefitnesseffectsofcopynumbervariationintheroma
AT calafellfrancesc populationhistorymodulatesthefitnesseffectsofcopynumbervariationintheroma