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Experience of Low-Pass Whole-Genome Sequencing-Based Copy Number Variant Analysis: A Survey of Chinese Tertiary Hospitals

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机构: [1]Prenatal Genetic Diagnosis Centre, Department of Obstetrics & Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China [2]Department of Genetics Medicine, First People’s Hospital of Yunnan Province, Kunming 650021, China [3]Reproductive Medicine Centre, Shengjing Hospital of China Medical University, Shenyang 110055, China [4]Reproductive Medicine Centre, Third Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, China [5]Department of Obstetrics and Gynecology and Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA [6]Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA [7]Manchester Centre for Audiology and Deafness (ManCAD), School of Health Sciences, University of Manchester, Manchester M13 9PL, UK [8]Genetics Centre, Reproductive & Genetic Hospital of CITIC-Xiangya, Changsha 410008, China
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关键词: low-pass whole-genome sequencing copy number variant tertiary hospital laboratory experience variant nomenclature

摘要:
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' 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, 9.91-17.60) and the read-length median was 65 bp (95% CI, 75.17-104.83). 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, 6.78-8.80). 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.

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出版当年[2022]版:
大类 | 3 区 医学
小类 | 3 区 医学:内科
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 医学:内科
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出版当年[2021]版:
Q2 MEDICINE, GENERAL & INTERNAL
最新[2023]版:
Q1 MEDICINE, GENERAL & INTERNAL

影响因子: 最新[2023版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

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第一作者机构: [1]Prenatal Genetic Diagnosis Centre, Department of Obstetrics & Gynecology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China
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通讯机构: [5]Department of Obstetrics and Gynecology and Pathology, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA 02115, USA [6]Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA [7]Manchester Centre for Audiology and Deafness (ManCAD), School of Health Sciences, University of Manchester, Manchester M13 9PL, UK
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