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Population genetic variation characterised through serial independent pool-seq: the Cyprus Genome Project
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  • Published: 19 March 2026

Population genetic variation characterised through serial independent pool-seq: the Cyprus Genome Project

  • Athos Antoniades2 na1,
  • Jianxiang Chi5 na1,
  • Cameron Brown2,
  • Paris Vogazianos2,3,
  • Emily Charalambous2,
  • Dimitris Vrachnos2,
  • Aristos Aristodimou2,
  • Andri Miltiadous1,
  • Andri Papaloizou1,
  • Anita Koumouli1,
  • Petroula Gerasimou1,
  • Yiannos Kyprianou1 &
  • …
  • Paul Costeas1,4,5 

Scientific Reports , Article number:  (2026) Cite this article

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Subjects

  • Computational biology and bioinformatics
  • Genetics
  • Medical research

Abstract

The Cyprus Genome Project characterizes the genetic landscape of the Cypriot population to address the lack of population-specific data in global repositories. We employed a serial independent pool-sequencing (pool-seq) strategy to sequence DNA from 10,000 healthy bone marrow donors, randomized into 10 independent biological replicates. This study design was selected to leverage specific operational and statistical advantages. Operationally, the method enables the processing of a large cohort that would be cost-prohibitive using individual sequencing. Statistically, the use of 10 independent biological replicates allowed for the differentiation of true low-frequency variants from sequencing artifacts. Furthermore, this design enabled the calculation of empirical confidence intervals for variant frequencies. We utilized both Whole Exome Sequencing and a targeted gene panel (813 genes) to maximize read depth and sensitivity. The study identified over 4 million variants, including > 100,000 variants absent from the gnomAD v4.1 and ClinVar databases. Validation against published clinical cohorts confirmed high concordance (r > 0.92). The results highlight significant differences between local and global allele frequencies, including pathogenic variants that are common in Cyprus but rare globally. The results, including an interactive genome map with full annotations from gnomAD v4.1 and ClinVar, are publicly accessible at www.cyprusgenome.org, with the aim of advancing healthcare and facilitating future clinical research.

Data availability

The datasets generated during and/or analysed during the current study are available in the European Variation Archive (EVA) repository at [https://www.ebi.ac.uk/ena/browser/view/PRJEB89856], with study accession number [PRJEB89856] and analyses number ERZ29062157.

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Author information

Author notes

  1. Athos Antoniades and Jianxiang Chi contributed equally to this work.

Authors and Affiliations

  1. Karaiskakio Foundation, 15, Nicandrou Papamina Avenue, Nicosia, 2032, Cyprus

    Andri Miltiadous, Andri Papaloizou, Anita Koumouli, Petroula Gerasimou, Yiannos Kyprianou & Paul Costeas

  2. Stremble Ventures Ltd, Ko 8 Germasogeia, Limassol, 4045, Cyprus

    Athos Antoniades, Cameron Brown, Paris Vogazianos, Emily Charalambous, Dimitris Vrachnos & Aristos Aristodimou

  3. European University Cyprus, 6 Diogenis Str, Engomi Nicosia, 2404, Cyprus

    Paris Vogazianos

  4. Cyprus Cancer Research Institute, 1 University Avenue, CCRI ”Nicola David - Pinedo Building, Aglantzia, 2109, Cyprus

    Paul Costeas

  5. The Centre for the Study of Heamatological and other Malignancies, Nicandrou Papamina Avenue, Nicosia, 2032, Cyprus

    Jianxiang Chi & Paul Costeas

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  1. Athos Antoniades
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Contributions

A. Antoniades and J.C contributed equally to this manuscript.P.C provided the main concept and idea of the manuscript as well as provided the biorender license to create Fig. 1. All authors reviewed the manuscript.C.B, D.V, E.C wrote the main manuscript textP.V contributed to the statistical analysis.A. Aristodimou and D.V performed all computational analysis.A.M, A.P, A.K, P.G, Y.K performed all laboratory experiments.

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Correspondence to Athos Antoniades.

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Antoniades, A., Chi, J., Brown, C. et al. Population genetic variation characterised through serial independent pool-seq: the Cyprus Genome Project. Sci Rep (2026). https://doi.org/10.1038/s41598-026-44707-x

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  • Received: 31 October 2025

  • Accepted: 13 March 2026

  • Published: 19 March 2026

  • DOI: https://doi.org/10.1038/s41598-026-44707-x

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