{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T15:27:39Z","timestamp":1778858859096,"version":"3.51.4"},"reference-count":29,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T00:00:00Z","timestamp":1651017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key Research &amp; Developmental Program of China","award":["2018YFC1004901"],"award-info":[{"award-number":["2018YFC1004901"]}]},{"name":"National Key Research &amp; Developmental Program of China","award":["14115418"],"award-info":[{"award-number":["14115418"]}]},{"name":"National Key Research &amp; Developmental Program of China","award":["2019A1515011042"],"award-info":[{"award-number":["2019A1515011042"]}]},{"name":"Hong Kong General Research Fund (GRF)","award":["2018YFC1004901"],"award-info":[{"award-number":["2018YFC1004901"]}]},{"name":"Hong Kong General Research Fund (GRF)","award":["14115418"],"award-info":[{"award-number":["14115418"]}]},{"name":"Hong Kong General Research Fund (GRF)","award":["2019A1515011042"],"award-info":[{"award-number":["2019A1515011042"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2018YFC1004901"],"award-info":[{"award-number":["2018YFC1004901"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["14115418"],"award-info":[{"award-number":["14115418"]}]},{"name":"Guangdong Basic and Applied Basic Research Foundation","award":["2019A1515011042"],"award-info":[{"award-number":["2019A1515011042"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>In China, low-pass whole-genome sequencing (low-pass WGS) is emerging as an alternative diagnostic test to detect copy number variants (CNVs). This survey aimed to study the laboratory practice, service quality, and case volumes of low-pass WGS-based CNV analysis among national accredited Chinese tertiary hospitals that have routinely applied low-pass WGS for more than a year and that have been certified in next-generation sequencing (NGS) clinical applications for more than three years. The questionnaire focused on (1) the composition of patients\u2019 referral indications for testing and annual case volumes; (2) the capacity of conducting laboratory assays, bioinformatic analyses, and reporting; (3) the sequencing platforms and parameters utilized; and (4) CNV nomenclature in reports. Participants were required to respond based on their routine laboratory practices and data audited in a 12-month period from February 2019 to January 2020. Overall, 24 participants representing 24 tertiary referral hospitals from 21 provincial administrative regions in China returned the questionnaires. Excluding three hospitals routinely applying low-pass WGS for non-invasive prenatal testing (NIPT) only, the analysis only focused on the data submitted by the rest 21 hospitals. These hospitals applied low-pass WGS-based CNV analysis for four primary applications: high-risk pregnancies, spontaneous abortions, couples with adverse pregnancy history, and children with congenital birth defects. The overall estimated annual sample volume was over 36,000 cases. The survey results showed that the most commonly reported detection limit for CNV size (resolution) was 100 kb; however, the sequencing methods utilized by the participants were variable (single-end: 61.90%, 13\/21; paired-end: 28.57%, 6\/21; both: 9.52%, 2\/21). The diversity was also reflected in the sequencing parameters: the mean read count was 13.75 million reads\/case (95% CI, 9.91\u201317.60) and the read-length median was 65 bp (95% CI, 75.17\u2013104.83). To assess further the compliance of the CNV reporting nomenclature according to the 2016 edition of International System for Human Cytogenomics Nomenclature (ISCN 2016), a scoring metric was applied and yielded responses from 19 hospitals; the mean compliance score was 7.79 out of 10 points (95% CI, 6.78\u20138.80). Our results indicated that the low-pass WGS-based CNV analysis service is in great demand in China. From a quality control perspective, challenges remain regarding the establishment of standard criteria for low-pass WGS-based CNV analysis and data reporting formats. In summary, the low-pass WGS-based method is becoming a common diagnostic approach, transforming the possibilities for genetic diagnoses for patients in China.<\/jats:p>","DOI":"10.3390\/diagnostics12051098","type":"journal-article","created":{"date-parts":[[2022,4,27]],"date-time":"2022-04-27T13:40:57Z","timestamp":1651066857000},"page":"1098","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Experience of Low-Pass Whole-Genome Sequencing-Based Copy Number Variant Analysis: A Survey of Chinese Tertiary Hospitals"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1223-2901","authenticated-orcid":false,"given":"Yu","family":"Zheng","sequence":"first","affiliation":[{"name":"Prenatal Genetic Diagnosis Centre, Department of Obstetrics & Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baosheng","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Genetics Medicine, First People\u2019s Hospital of Yunnan Province, Kunming 650021, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jichun","family":"Tan","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Centre, Shengjing Hospital of China Medical University, Shenyang 110055, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yichun","family":"Guan","sequence":"additional","affiliation":[{"name":"Reproductive Medicine Centre, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"The Chinese Genomic Structural Variants Consortium","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2198-6756","authenticated-orcid":false,"given":"Cynthia C.","family":"Morton","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology and Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, MA 02115, USA"},{"name":"Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA"},{"name":"Manchester Centre for Audiology and Deafness (ManCAD), School of Health Sciences, University of \r\n      Manchester, Manchester M13 9PL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guangxiu","family":"Lu","sequence":"additional","affiliation":[{"name":"Genetics Centre, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"986","DOI":"10.1093\/nar\/gkt958","article-title":"The Database of Genomic Variants: A curated collection of structural variation in the human genome","volume":"42","author":"MacDonald","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1038\/nrg3871","article-title":"A copy number variation map of the human genome","volume":"16","author":"Zarrei","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1038\/nrg3373","article-title":"Phenotypic impact of genomic structural variation: Insights from and for human disease","volume":"14","author":"Weischenfeldt","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"742","DOI":"10.1097\/GIM.0b013e3181f8baad","article-title":"Array-based technology and recommendations for utilization in medical genetics practice for detection of chromosomal abnormalities","volume":"12","author":"Manning","year":"2010","journal-title":"Genet. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1016\/j.ajhg.2010.04.006","article-title":"Consensus Statement: Chromosomal Microarray Is a First-Tier Clinical Diagnostic Test for Individuals with Developmental Disabilities or Congenital Anomalies","volume":"86","author":"Miller","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.ygeno.2013.04.006","article-title":"Diagnosis of copy number variation by Illumina next generation sequencing is comparable in performance to oligonucleotide array comparative genomic hybridisation","volume":"102","author":"Hayes","year":"2013","journal-title":"Genomics"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1007\/s00439-020-02185-9","article-title":"Low-pass genome sequencing: A validated method in clinical cytogenetics","volume":"139","author":"Chau","year":"2020","journal-title":"Hum. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Xie, C., and Tammi, M.T. (2009). CNV-seq, a new method to detect copy number variation using high-throughput sequencing. BMC Bioinform., 10.","DOI":"10.1186\/1471-2105-10-80"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Zhao, M., Wang, Q., Wang, Q., Jia, P., and Zhao, Z. (2013). Computational tools for copy number variation (CNV) detection using next-generation sequencing data: Features and perspectives. BMC Bioinform., 14.","DOI":"10.1186\/1471-2105-14-S11-S1"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1038\/s41436-019-0634-7","article-title":"Low-pass genome sequencing versus chromosomal microarray analysis: Implementation in prenatal diagnosis","volume":"22","author":"Wang","year":"2020","journal-title":"Genet. Med."},{"key":"ref_11","unstructured":"Clinical Genetics Group of Medical Genetics Branch Chinese Medical Association, Professional Committee for Prenatal Diagnosis of Genetic Diseases Medical Genetics Branch of Chinese Medical Association, and Group of Genetic Disease Prevention and Control Birth Defect Prevention and Control Committee of Chinese Society of Preventive Medicine (2019). Expert consensus on the application of low-depth whole genome sequencing in prenatal diagnosis. Chin. J. Med. Genet., 36, 293\u2013296."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.jmoldx.2014.05.002","article-title":"Copy number variation sequencing for comprehensive diagnosis of chromosome disease syndromes","volume":"16","author":"Liang","year":"2014","journal-title":"J. Mol. Diagn."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1038\/gim.2015.199","article-title":"Low-pass whole-genome sequencing in clinical cytogenetics: A validated approach","volume":"18","author":"Dong","year":"2016","journal-title":"Genet. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"493.e1","DOI":"10.1016\/j.ajog.2019.06.007","article-title":"Characteristics and mode of inheritance of pathogenic copy number variants in prenatal diagnosis","volume":"221","author":"Chau","year":"2019","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1016\/j.jmoldx.2016.05.001","article-title":"Next-Generation Proficiency Testing","volume":"18","author":"Segal","year":"2016","journal-title":"J. Mol. Diagn."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1544","DOI":"10.5858\/arpa.2016-0501-RA","article-title":"Review of clinical next-generation sequencing","volume":"141","author":"Yohe","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_17","first-page":"1","article-title":"Discussion on the standard of clinical genetic testing report and the consensus of gene testing industry","volume":"35","author":"Huang","year":"2018","journal-title":"Chin. J. Med. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/s41436-019-0686-8","article-title":"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)","volume":"22","author":"Riggs","year":"2020","journal-title":"Genet. Med."},{"key":"ref_19","unstructured":"McGowan-Jordan, J., Simons, A., and Schmid, M. (2016). ISCN: An International System for Human Cytogenomic Nomenclature (2016), Karger."},{"key":"ref_20","unstructured":"(2022, March 31). National Stocktaking Report on Birth Defect Prevention, Available online: http:\/\/www.gov.cn\/gzdt\/att\/att\/site1\/20120912\/1c6f6506c7f811bacf9301."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12978-017-0297-2","article-title":"Factors associated with spontaneous abortion: A cross-sectional study of Chinese populations","volume":"14","author":"Zheng","year":"2017","journal-title":"Reprod. Health"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.fertnstert.2013.10.017","article-title":"Current overview of pregnancy complications and live-birth outcome of assisted reproductive technology in mainland China","volume":"101","author":"Yang","year":"2014","journal-title":"Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"12239","DOI":"10.1038\/s41598-018-29889-3","article-title":"Pregnancy Outcomes in Women of Advanced Maternal Age: A Retrospective Cohort Study from China","volume":"8","author":"Shan","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S362","DOI":"10.1016\/j.gim.2022.01.583","article-title":"OP035: Rapid Whole Genome Sequencing (rWGS) in the cardiac NICU","volume":"24","author":"Guha","year":"2022","journal-title":"Genet. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"154ra135","DOI":"10.1126\/scitranslmed.3004041","article-title":"Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units","volume":"4","author":"Saunders","year":"2012","journal-title":"Sci. Transl. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.jmoldx.2014.02.002","article-title":"Methods-based proficiency testing in molecular genetic pathology","volume":"16","author":"Schrijver","year":"2014","journal-title":"J. Mol. Diagnostics"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1373\/clinchem.2011.168641","article-title":"Proficiency testing\/external quality assessment: Current challenges and future directions","volume":"57","author":"Miller","year":"2011","journal-title":"Clin. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0009-8981(01)00516-2","article-title":"IVD industry role for quality and accreditation in medical laboratories","volume":"309","author":"Bremond","year":"2001","journal-title":"Clin. Chim. Acta"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"McGowan-Jordan, J., Hastings, R.J., Moore, S., and GmbH, S.K. (2020). ISCN 2020: An international System for Human Cytogenomic Nomenclature (2020), Karger.","DOI":"10.1159\/isbn.978-3-318-06867-2"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1098\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:02:00Z","timestamp":1760137320000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/5\/1098"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,4,27]]},"references-count":29,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2022,5]]}},"alternative-id":["diagnostics12051098"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12051098","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,4,27]]}}}