Low-pass whole genome sequencing is a reliable and cost-effective approach for copy number variant analysis in the clinical setting
Open accessPublished version of a preprint
Abstract
Introduction: Next generation sequencing technology has greatly reduced the cost and time required for sequencing a genome. An approach that is rapidly being adopted as an alternative method for CNV analysis is the low‐pass whole genome sequencing (LP‐WGS). Here, we evaluated the performance of LP‐WGS to detect copy number variants (CNVs) in clinical cytogenetics. Materials and Methods: DNA samples with known CNVs detected by chromosomal microarray analyses (CMA) were selected for comparison and used as positive controls; our panel included 44 DNA samples (12 prenatal and 32 postnatal), comprising a total of 55 chromosome imbalances. The selected cases were chosen to provide a wide range of clinically relevant CNVs, the vast majority being associated with intellectual disability or recognizable syndromes. The chromosome imbalances ranged in size from 75 kb to 90.3 Mb, including aneuploidies and two cases of mosaicism. Results: All CNVs were successfully detected by LP‐WGS, showing a high level of consistency and robust performance of the sequencing method. Notably, the size of chromosome imbalances detected by CMA and LP‐WGS were compatible between the two different platforms, which indicates that the resolution and sensitivity of the LP‐WGS approach are at least similar to those provided by CMA. Discussion: Our data show the potential use of LP‐WGS to detect CNVs in clinical diagnosis and confirm the method as an alternative for chromosome imbalances detection. The diagnostic effectiveness and feasibility of LP‐WGS, in this technical validation study, were evidenced by a clinically representative dataset of CNVs that allowed a systematic assessment of the detection power and the accuracy of the sequencing approach. Further, since the software used in this study is commercially available, the method can easily be tested and implemented in a routine diagnostic setting.
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Low-pass whole-genome sequencing (lpWGS) costs less than €150 per sample.
“Low-pass whole-genome sequencing (lpWGS) has recently reached the significant milestone of costing less than €150 per sample [51].”
From Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review (2026) · cites this paper as [51]
The Discussion (page unavailable) says LP-WGS costs approximately 50% less than microarray testing and that multiplexing reduces sequencing cost per patient. It does not give a price in euros or establish that the cost is below €150 per sample; its mention of 150 refers to the number of samples a flow cell can run. (LLM, conf=0.86)
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Research works printed but not linked: 8
- Carvalho, C. M. B. & Lupski, J. R. Mechanisms underlying structural variant formation in genomic disorders. Nature Reviews Genetics Preprint at https://doi.org/10.1038/nrg.2015.25 (2016). · DOI · Paper page
- Silva, M. et al. European guidelines for constitutional cytogenomic analysis. European Journal of Human Genetics 27, 1-16 (2019).
- Matthijs, G. et al. Guidelines for diagnostic next-generation sequencing. European Journal of Human Genetics vol. 24 2-5 Preprint at https://doi.org/10.1038/ejhg.2015.226 (2016). · DOI
- Dondorp, W. et al. Non-invasive prenatal testing for aneuploidy and beyond: Challenges of responsible innovation in prenatal screening. European Journal of Human Genetics 23, 1438-1450 (2015).
- Lenaerts, L., Tuveri, S., Jatsenko, T., Amant, F. & Vermeesch, J. R. Detection of incipient tumours by screening of circulating plasma DNA: hype or hope? Acta Clinica Belgica: International Journal of Clinical and Laboratory Medicine 75, 9- 18 (2020).
- Chaubey, A. et al. Low-Pass Genome Sequencing: Validation and Diagnostic Utility from 409 Clinical Cases of Low-Pass Genome Sequencing for the Detection of Copy Number Variants to Replace Constitutional Microarray. Journal of Molecular Diagnostics 22, 823-840 (2020).
- Wang, H. et al. Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis. GENETICS in MEDICINE doi:10.1038/s41436-019. · DOI
- Lenaerts, L. et al. Genomewide copy number alteration screening of circulating plasma DNA: Potential for the detection of incipient tumors. Annals of Oncology 30, 85-95 (2019).
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Genetic Insights into the Economic Toll of Cell Line Misidentification: A Comprehensive Review
Weiskirchen, R. (2026) · Medical Sciences · doi:10.3390/medsci14010025 · Cited by 4 · see citing works
- Authors
- Mazzonetto, P. C., Villela, D., da Costa, S. S., Krepischi, A. C. V., Milanezi, F., Migliavacca, M. P., Pierry, P. M., Bonaldi, A., Almeida, L. G. D., De Souza, C. A., Kroll, J. E., Paula, M. G., Guarischi‐Sousa, R., Scapulatempo‐Neto, C., & Rosenberg, C.
- Affiliations
- Universidade de São Paulo (BR)
- DASA (Brazil) (BR)
- The Human Genome and Stem Cell Research Center, Department of Genetics and Evolutionary Biology, Institute of Biosciences University of São Paulo São Paulo SP Brazil
- Diagnósticos da América S.A. DASA São Paulo Brazil
- Corresponding author
- Rosenberg, Carla
- ORCID
- Venue
- Annals of Human Genetics
- Publisher
- Wiley
- Published
- 2023-10-09
- Volume
- 88
- Issue
- 2
- Pages
- 113-125
- ISSN
- 0003-4800 (ISSN-L)
- 1469-1809
- OpenAlex
- W4387440948
- Cited by
- 17
- References
- 0
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 5 · 2023: 1
- FWCI
- 2.82
- Type
- journal article
- Language
- en
- Open access
- green
- dx.doi.org
- Licence
- Locations
- Annals of Human Genetics (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Prenatal Screening and Diagnostics
- Keywords
- low-pass sequencing, copy number variation, chromosomal imbalances, clinical cytogenetics, aneuploidy, mosaicism, intellectual disability, diagnostic accuracy, cost-effectiveness
- MeSH terms
- Whole Genome Sequencing, Aneuploidy, Cost-Benefit Analysis, DNA, Female, Humans, Pregnancy, DNA Copy Number Variations
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