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

被引：1

作者：

Mazzonetto, Patricia C. ^{[1
,2
]}

Villela, Darine ^{[2
]}

Krepischi, Ana C. V. ^{[1
]}

Pierry, Paulo M. ^{[2
]}

Bonaldi, Adriano ^{[2
]}

Almeida, Luiz Gustavo D. ^{[2
]}

Paula, Marcelo G. ^{[2
]}

Burger, Matheus Carvalho ^{[2
]}

de Oliveira, Ana Gabriela ^{[2
]}

Fonseca, Gustavo G. G. ^{[2
]}

Giugliani, Roberto ^{[2
,3
,4
]}

Riegel-Giugliani, Mariluce ^{[3
,4
]}

Bertola, Debora ^{[5
]}

Yamamoto, Guilherme Lopes ^{[2
,5
]}

Passos-Bueno, Maria Rita ^{[1
]}

Campos, Gabriele da Silva ^{[1
]}

Machado, Ana Claudia Dantas ^{[1
]}

Mazzeu, Juliana F. ^{[6
]}

Perrone, Eduardo ^{[7
]}

Zechi-Ceide, Roseli M. ^{[8
]}

Kokitsu-Nakata, Nancy M. ^{[8
]}

Vieira, Tarsis Paiva ^{[9
]}

Steiner, Carlos Eduardo ^{[9
]}

Gil-da-Silva-Lopes, Vera Lucia ^{[9
]}

Vieira, Daniela Koeller Rodrigues ^{[10
,11
]}

Boy, Raquel ^{[12
]}

de Pina-Neto, Joao Monteiro ^{[13
]}

Scapulatempo-Neto, Cristovam ^{[2
]}

Milanezi, Fernanda ^{[2
]}

Rosenberg, Carla ^{[1
,2
]}

机构：

[1] Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cell Res Ctr, Dept Genet & Evolutionary Biol, Sao Paulo, Brazil

[2] Diagnost Amer SA, DASA, Av Divino Salvador 876, BR-04078013 Sao Paulo, SP, Brazil

[3] Ctr Atencao Integral & Treinamento Doencas Raras, Casa Raros House Rares, Porto Alegre, Brazil

[4] Inst Nacl Genet Med Populac, INAGEMP, Porto Alegre, Brazil

[5] Univ Sao Paulo, Fac Med, Inst Crianca, Sao Paulo, Brazil

[6] Univ Brasilia, Fac Med, Brasilia, Brazil

[7] Univ Fed Sao Paulo, Dept Morfol & Genet, Sao Paulo, Brazil

[8] Univ Sao Paulo, Hosp Rehabil Craniofacial Anomalies, Dept Clin Genet & Mol Biol, Sao Paulo, Brazil

[9] Univ Estadual Campinas, Sch Med Sci, Dept Translat Med Med Genet & Genom Med, Sao Paulo, Brazil

[10] Municipal Secretary Hlth Angra dos Reis, Rio De Janeiro, Brazil

[11] Oswaldo Cruz Fdn IFF FIOCRUZ, Natl Inst Women Children & Adolescents Hlth Fernan, Rio De Janeiro, Brazil

[12] Univ Estado Rio De Janeiro, Rio De Janeiro, Brazil

[13] Univ Sao Paulo, Fac Med Ribeirao Preto, Sao Paulo, Brazil

来源：

AMERICAN JOURNAL OF MEDICAL GENETICS PART A | 2024年 / 194卷 / 11期

基金：

巴西圣保罗研究基金会;

关键词：

CNV; copy number variants; cytogenetics; low-pass whole genome sequencing; next generation sequencing (NGS); postnatal diagnosis; structural variant; COPY-NUMBER VARIANTS; STANDARDS;

D O I：

10.1002/ajmg.a.63802

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页数：9

共 32 条

[21] A Framework for Promoting Diversity, Equity, and Inclusion in Genetics and Genomics Research [J].

Rebbeck, Timothy R. ;

Bridges, John F. P. ;

Mack, Jennifer W. ;

Gray, Stacy W. ;

Trent, Jeffrey M. ;

George, Suzanne ;

Crossnohere, Norah L. ;

Paskett, Electra D. ;

Painter, Corrie A. ;

Wagle, Nikhil ;

Kano, Miria ;

Henderson, Patricia Nez ;

Henderson, Jeffrey A. ;

Mishra, Shiraz, I ;

Willman, Cheryl L. ;

Sussman, Andrew L. .

JAMA HEALTH FORUM, 2022, 3 (04)

[22] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) [J].

Riggs, Erin Rooney ;

Andersen, Erica F. ;

Cherry, Athena M. ;

Kantarci, Sibel ;

Kearney, Hutton ;

Patel, Ankita ;

Raca, Gordana ;

Ritter, Deborah I. ;

South, Sarah T. ;

Thorland, Erik C. ;

Pineda-Alvarez, Daniel ;

Aradhya, Swaroop ;

Martin, Christa Lese .

GENETICS IN MEDICINE, 2020, 22 (02) :245-257

[23] Practice parameter: Evaluation of the child with global developmental delay - Report of the quality standards subcommittee of the American Academy of Neurology and The Practice Committee of the Child Neurology Society [J].

Shevell, M ;

Ashwal, S ;

Donley, D ;

Flint, J ;

Gingold, M ;

Hirtz, D ;

Majnemer, A ;

Noetzel, M ;

Sheth, RD .

NEUROLOGY, 2003, 60 (03) :367-380

[24] European guidelines for constitutional cytogenomic analysis [J].

Silva, Marisa ;

de Leeuw, Nicole ;

Mann, Kathy ;

Schuring-Blom, Heleen ;

Morgan, Sian ;

Giardino, Daniela ;

Rack, Katrina ;

Hastings, Ros .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2019, 27 (01) :1-16

[25] Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders [J].

Srivastava, Siddharth ;

Love-Nichols, Jamie A. ;

Dies, Kira A. ;

Ledbetter, David H. ;

Martin, Christa L. ;

Chung, Wendy K. ;

Firth, Helen, V ;

Frazier, Thomas ;

Hansen, Robin L. ;

Prock, Lisa ;

Brunner, Han ;

Hoang, Ny ;

Scherer, Stephen W. ;

Sahin, Mustafa ;

Miller, David T. ;

Restrepo, Bibiana ;

Shankar, Suma ;

Riggs, Erin Rooney ;

Constantinou, Pete ;

Reed-Weston, Anne ;

Tong, R. Spencer ;

Howe, Jennifer ;

Buchanan, Janet ;

Fisher, Rachel ;

Mahida, Sonal .

GENETICS IN MEDICINE, 2019, 21 (11) :2413-2421

[26] Global diversity, population stratification, and selection of human copy-number variation [J].

Sudmant, Peter H. ;

Mallick, Swapan ;

Nelson, Bradley J. ;

Hormozdiari, Fereydoun ;

Krumm, Niklas ;

Huddleston, John ;

Coe, Bradley P. ;

Baker, Carl ;

Nordenfelt, Susanne ;

Bamshad, Michael ;

Jorde, Lynn B. ;

Posukh, Olga L. ;

Sahakyan, Hovhannes ;

Watkins, W. Scott ;

Yepiskoposyan, Levon ;

Abdullah, M. Syafiq ;

Bravi, Claudio M. ;

Capelli, Cristian ;

Hervig, Tor ;

Wee, Joseph T. S. ;

Tyler-Smith, Chris ;

van Driem, George ;

Romero, Irene Gallego ;

Jha, Aashish R. ;

Karachanak-Yankova, Sena ;

Toncheva, Draga ;

Comas, David ;

Henn, Brenna ;

Kivisild, Toomas ;

Ruiz-Linares, Andres ;

Sajantila, Antti ;

Metspalu, Ene ;

Parik, Jueri ;

Villems, Richard ;

Starikovskaya, Elena B. ;

Ayodo, George ;

Beall, Cynthia M. ;

Di Rienzo, Anna ;

Hammer, Michael F. ;

Khusainova, Rita ;

Khusnutdinova, Elza ;

Klitz, William ;

Winkler, Cheryl ;

Labuda, Damian ;

Metspalu, Mait ;

Tishkoff, Sarah A. ;

Dryomov, Stanislav ;

Sukernik, Rem ;

Patterson, Nick ;

Reich, David .

SCIENCE, 2015, 349 (6253)

[27] The performance of genome sequencing as a first-tier test for neurodevelopmental disorders [J].

van der Sanden, Bart P. G. H. ;

Schobers, Gaby ;

Galbany, Jordi Corominas ;

Koolen, David A. ;

Sinnema, Margje ;

van Reeuwijk, Jeroen ;

Stumpel, Connie T. R. M. ;

Kleefstra, Tjitske ;

de Vries, Bert B. A. ;

Ruiterkamp-Versteeg, Martina ;

Leijsten, Nico ;

Kwint, Michael ;

Derks, Ronny ;

Swinkels, Hilde ;

den Ouden, Amber ;

Pfundt, Rolph ;

Rinne, Tuula ;

de Leeuw, Nicole ;

Stegmann, Alexander P. ;

Stevens, Servi J. ;

van den Wijngaard, Arthur ;

Brunner, Han G. ;

Yntema, Helger G. ;

Gilissen, Christian ;

Nelen, Marcel R. ;

Vissers, Lisenka E. L. M. .

EUROPEAN JOURNAL OF HUMAN GENETICS, 2023, 31 (01) :81-88

[28] Detection of mosaicism for segmental and whole chromosome imbalances by targeted sequencing [J].

Villela, Darine ;

de Barros, Juliana Sobral ;

da Costa, Silvia Souza ;

Aguiar, Talita F. M. ;

Campagnari, Francine ;

Vianna-Morgante, Angela M. ;

Krepischi, Ana C. V. ;

Rosenberg, Carla .

ANNALS OF HUMAN GENETICS, 2021, 85 (01) :18-26

[29] Efficient detection of chromosome imbalances and single nucleotide variants using targeted sequencing in the clinical setting [J].

Villela, Darine ;

Costa, Silvia Souza ;

Vianna-Morgante, Angela M. ;

Krepischi, Ana C. V. ;

Rosenberg, Carla .

EUROPEAN JOURNAL OF MEDICAL GENETICS, 2017, 60 (12) :667-674

[30] Low-pass genome sequencing versus chromosomal microarray analysis: implementation in prenatal diagnosis [J].

Wang, Huilin ;

Dong, Zirui ;

Zhang, Rui ;

Chau, Matthew Hoi Kin ;

Yang, Zhenjun ;

Tsang, Kathy Yin Ching ;

Wong, Hoi Kin ;

Gui, Baoheng ;

Meng, Zhuo ;

Xiao, Kelin ;

Zhu, Xiaofan ;

Wang, Yanfang ;

Chen, Shaoyun ;

Leung, Tak Yeung ;

Cheung, Sau Wai ;

Kwok, Yvonne K. ;

Morton, Cynthia C. ;

Zhu, Yuanfang ;

Choy, Kwong Wai .

GENETICS IN MEDICINE, 2020, 22 (03) :500-510

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