Patricia C. Mazzonetto, Darine Villela, Ana C. V. Krepischi, Paulo M. Pierry, Adriano Bonaldi, Luiz Gustavo D. Almeida, Marcelo G. Paula, Matheus Carvalho Bürger, Ana Gabriela de Oliveira, Gustavo G. G. Fonseca, Roberto Giugliani, Mariluce Riegel-Giugliani, Débora Bertola, Guilherme Lopes Yamamoto, Maria Rita Passos-Bueno, Gabriele da Silva Campos, Ana Claudia Dantas Machado, Juliana F. Mazzeu, Eduardo Perrone, Roseli M. Zechi-Ceide, Nancy M. Kokitsu-Nakata, Társis Paiva Vieira, Carlos Eduardo Steiner, Vera Lúcia Gil-da-Silva-Lopes, Daniela Koeller Rodrigues Vieira, Raquel Boy, João Monteiro de Pina-Neto, Cristovam Scapulatempo-Neto, Fernanda Milanezi, Carla Rosenberg
{"title":"低通滤波器全基因组测序作为中低收入国家染色体微阵列分析的一种经济有效的替代方法。","authors":"Patricia C. Mazzonetto, Darine Villela, Ana C. V. Krepischi, Paulo M. Pierry, Adriano Bonaldi, Luiz Gustavo D. Almeida, Marcelo G. Paula, Matheus Carvalho Bürger, Ana Gabriela de Oliveira, Gustavo G. G. Fonseca, Roberto Giugliani, Mariluce Riegel-Giugliani, Débora Bertola, Guilherme Lopes Yamamoto, Maria Rita Passos-Bueno, Gabriele da Silva Campos, Ana Claudia Dantas Machado, Juliana F. Mazzeu, Eduardo Perrone, Roseli M. Zechi-Ceide, Nancy M. Kokitsu-Nakata, Társis Paiva Vieira, Carlos Eduardo Steiner, Vera Lúcia Gil-da-Silva-Lopes, Daniela Koeller Rodrigues Vieira, Raquel Boy, João Monteiro de Pina-Neto, Cristovam Scapulatempo-Neto, Fernanda Milanezi, Carla Rosenberg","doi":"10.1002/ajmg.a.63802","DOIUrl":null,"url":null,"abstract":"<p>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.</p>","PeriodicalId":7507,"journal":{"name":"American Journal of Medical Genetics Part A","volume":"194 11","pages":""},"PeriodicalIF":1.7000,"publicationDate":"2024-06-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries\",\"authors\":\"Patricia C. Mazzonetto, Darine Villela, Ana C. V. Krepischi, Paulo M. Pierry, Adriano Bonaldi, Luiz Gustavo D. Almeida, Marcelo G. Paula, Matheus Carvalho Bürger, Ana Gabriela de Oliveira, Gustavo G. G. Fonseca, Roberto Giugliani, Mariluce Riegel-Giugliani, Débora Bertola, Guilherme Lopes Yamamoto, Maria Rita Passos-Bueno, Gabriele da Silva Campos, Ana Claudia Dantas Machado, Juliana F. Mazzeu, Eduardo Perrone, Roseli M. Zechi-Ceide, Nancy M. Kokitsu-Nakata, Társis Paiva Vieira, Carlos Eduardo Steiner, Vera Lúcia Gil-da-Silva-Lopes, Daniela Koeller Rodrigues Vieira, Raquel Boy, João Monteiro de Pina-Neto, Cristovam Scapulatempo-Neto, Fernanda Milanezi, Carla Rosenberg\",\"doi\":\"10.1002/ajmg.a.63802\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>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. 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Low-pass whole genome sequencing as a cost-effective alternative to chromosomal microarray analysis for low- and middle-income countries
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.
期刊介绍:
The American Journal of Medical Genetics - Part A (AJMG) gives you continuous coverage of all biological and medical aspects of genetic disorders and birth defects, as well as in-depth documentation of phenotype analysis within the current context of genotype/phenotype correlations. In addition to Part A , AJMG also publishes two other parts:
Part B: Neuropsychiatric Genetics , covering experimental and clinical investigations of the genetic mechanisms underlying neurologic and psychiatric disorders.
Part C: Seminars in Medical Genetics , guest-edited collections of thematic reviews of topical interest to the readership of AJMG .