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Plasma cell\u2010free DNA was amplified by Targeted And Genome\u2010wide simultaneous sequencing (TAGs\u2010seq) to generate around 99% of total reads covering the whole\u2010genome region and around 1%\u00a0\u00a0covering the target genes. The reads on the whole\u2010genome region were analyzed for fetal aneuploidy using a binary hypothesis T\u2010score and the reads on target genes were analyzed for point mutations by calculating the minor allelic frequency of loci on <jats:italic>FGFR3<\/jats:italic> and <jats:italic>HBB<\/jats:italic>. TAGs\u2010seq results were compared with conventional NIPT and diagnostic results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In each sample, TAGs\u2010seq generated 44.7\u201354 million sequencing reads covering the whole\u2010genome region of 0.1\u20133\u00d7 and the target genes of &gt;1000\u00d7depth. All cases of fetal aneuploidy and <jats:italic>de novo<\/jats:italic> mutations of achondroplasia\/thanatophoric dysplasia were identified with high sensitivities and specificities except for one false\u2010negative paternal mutation of <jats:italic>\u03b2\u2010<\/jats:italic>thalassemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TAGs\u2010seq is a novel NIPT method that combines the fetal aneuploidy screening and the detection of <jats:italic>de novo<\/jats:italic> <jats:italic>FGFR3<\/jats:italic> mutations and paternal <jats:italic>HBB<\/jats:italic> mutations.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pd.5879","type":"journal-article","created":{"date-parts":[[2020,12,19]],"date-time":"2020-12-19T12:05:28Z","timestamp":1608379528000},"page":"440-448","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Simultaneous detection of fetal aneuploidy, <i>de novo<\/i><i>FGFR3<\/i> mutations and paternally derived <i>\u03b2<\/i>\u2010thalassemia by a novel method of noninvasive prenatal testing"],"prefix":"10.1002","volume":"41","author":[{"given":"Lin","family":"Yang","sequence":"first","affiliation":[{"name":"BGI Education Center University of Chinese Academy of Sciences  Shenzhen China"},{"name":"BGI\u2010Shenzhen  Shenzhen China"},{"name":"School of Future Technology University of Chinese Academy of Sciences  Beijing China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7800-9505","authenticated-orcid":false,"given":"Yujing","family":"Wu","sequence":"additional","affiliation":[{"name":"BGI Education Center University of Chinese Academy of Sciences  Shenzhen China"},{"name":"BGI\u2010Shenzhen  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhiyang","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics Shenzhen People's Hospital The Second Clinical Medical 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