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. 2024 Nov;194(11):e63802.
doi: 10.1002/ajmg.a.63802. Epub 2024 Jun 25.

Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries

Patricia C Mazzonetto  1   2 , Darine Villela  2 , Ana C V Krepischi  1 , Paulo M Pierry  2 , Adriano Bonaldi  2 , Luiz Gustavo D Almeida  2 , Marcelo G Paula  2 , Matheus Carvalho Bürger  2 , Ana Gabriela de Oliveira  2 , Gustavo G G Fonseca  2 , Roberto Giugliani  2   3   4 , Mariluce Riegel-Giugliani  3   4 , Débora Bertola  5 , Guilherme Lopes Yamamoto  2   5 , Maria Rita Passos-Bueno  1 , Gabriele da Silva Campos  1 , Ana Claudia Dantas Machado  1 , Juliana F Mazzeu  6 , Eduardo Perrone  7 , Roseli M Zechi-Ceide  8 , Nancy M Kokitsu-Nakata  8 , Társis Paiva Vieira  9 , Carlos Eduardo Steiner  9 , Vera Lúcia Gil-da-Silva-Lopes  9 , Daniela Koeller Rodrigues Vieira  10   11 , Raquel Boy  12 , João Monteiro de Pina-Neto  13 , Cristovam Scapulatempo-Neto  2 , Fernanda Milanezi  2 , Carla Rosenberg  1   2
Affiliations

Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries

Patricia C Mazzonetto et al. Am J Med Genet A. 2024 Nov.

Abstract

Low-pass whole genome sequencing (LP-WGS) has been applied as alternative method to detect copy number variants (CNVs) in the clinical setting. Compared with chromosomal microarray analysis (CMA), the sequencing-based approach provides a similar resolution of CNV detection at a lower cost. In this study, we assessed the efficiency and reliability of LP-WGS as a more affordable alternative to CMA. A total of 1363 patients with unexplained neurodevelopmental delay/intellectual disability, autism spectrum disorders, and/or multiple congenital anomalies were enrolled. Those patients were referred from 15 nonprofit organizations and university centers located in different states in Brazil. The analysis of LP-WGS at 1x coverage (>50kb) revealed a positive testing result in 22% of the cases (304/1363), in which 219 and 85 correspond to pathogenic/likely pathogenic (P/LP) CNVs and variants of uncertain significance (VUS), respectively. The 16% (219/1363) diagnostic yield observed in our cohort is comparable to the 15%-20% reported for CMA in the literature. The use of commercial software, as demonstrated in this study, simplifies the implementation of the test in clinical settings. Particularly for countries like Brazil, where the cost of CMA presents a substantial barrier to most of the population, LP-WGS emerges as a cost-effective alternative for investigating copy number changes in cytogenetics.

Keywords: CNV; copy number variants; cytogenetics; low‐pass whole genome sequencing; next generation sequencing (NGS); postnatal diagnosis; structural variant.

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References

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