Zhang H.,BGI Shenzhen |
Zhang H.,BGI Clinical Laboratories Shenzen |
Gao Y.,BGI Shenzhen |
Gao Y.,BGI Clinical Laboratories Shenzen |
And 26 more authors.
Ultrasound in Obstetrics and Gynecology | Year: 2015
Objectives To report the clinical performance of massively parallel sequencing-based non-invasive prenatal testing (NIPT) in detecting trisomies 21, 18 and 13 in over 140 000 clinical samples and to compare its performance in low-risk and high-risk pregnancies. Methods Between 1 January 2012 and 31 August 2013, 147 314 NIPT requests to screen for fetal trisomies 21, 18 and 13 using low-coverage whole-genome sequencing of plasma cell-free DNA were received. The results were validated by karyotyping or follow-up of clinical outcomes. Results NIPT was performed and results obtained in 146 958 samples, for which outcome data were available in 112 669 (76.7%). Repeat blood sampling was required in 3213 cases and 145 had test failure. Aneuploidy was confirmed in 720/781 cases positive for trisomy 21, 167/218 cases positive for trisomy 18 and 22/67 cases positive for trisomy 13 on NIPT. Nine false negatives were identified, including six cases of trisomy 21 and three of trisomy 18. The overall sensitivity of NIPT was 99.17%, 98.24% and 100% for trisomies 21, 18 and 13, respectively, and specificity was 99.95%, 99.95% and 99.96% for trisomies 21, 18 and 13, respectively. There was no significant difference in test performance between the 72 382 high-risk and 40 287 low-risk subjects (sensitivity, 99.21% vs 98.97% (P = 0.82); specificity, 99.95% vs 99.95% (P = 0.98)). The major factors contributing to false-positive and false-negative NIPT results were maternal copy number variant and fetal/placental mosaicism, but fetal fraction had no effect. Conclusions Using a stringent protocol, the good performance of NIPT shown by early validation studies can be maintained in large clinical samples. This technique can provide equally high sensitivity and specificity in screening for trisomy 21 in a low-risk, as compared to high-risk, population. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Source
DuanMu H.,Northeast Agricultural University |
Wang Y.,Northeast Agricultural University |
Bai X.,Northeast Agricultural University |
Cheng S.,Northeast Agricultural University |
And 9 more authors.
Functional and Integrative Genomics | Year: 2015
Soil alkalinity is an important environmental problem limiting agricultural productivity. Wild soybean (Glycine soja) shows strong alkaline stress tolerance, so it is an ideal plant candidate for studying the molecular mechanisms of alkaline tolerance and identifying alkaline stress-responsive genes. However, limited information is available about G. soja responses to alkaline stress on a genomic scale. Therefore, in the present study, we used RNA sequencing to compare transcript profiles of G. soja root responses to sodium bicarbonate (NaHCO3) at six time points, and a total of 68,138,478 pairs of clean reads were obtained using the Illumina GAIIX. Expression patterns of 46,404 G. soja genes were profiled in all six samples based on RNA-seq data using Cufflinks software. Then, t12 transcription factors from MYB, WRKY, NAC, bZIP, C2H2, HB, and TIFY families and 12 oxidation reduction related genes were chosen and verified to be induced in response to alkaline stress by using quantitative real-time polymerase chain reaction (qRT-PCR). The GO functional annotation analysis showed that besides “transcriptional regulation” and “oxidation reduction,” these genes were involved in a variety of processes, such as “binding” and “response to stress.” This is the first comprehensive transcriptome profiling analysis of wild soybean root under alkaline stress by RNA sequencing. Our results highlight changes in the gene expression patterns and identify a set of genes induced by NaHCO3 stress. These findings provide a base for the global analyses of G. soja alkaline stress tolerance mechanisms. © 2015, Springer-Verlag Berlin Heidelberg. Source
Wang L.,Huazhong University of Science and Technology |
Yang Y.,BGI Wuhan |
Song J.,Prenatal Diagnosis Center |
Mao L.,BGI Wuhan |
And 6 more authors.
Journal of Child Neurology | Year: 2015
Joubert syndrome is a neurologic disorder with a pathognomonic "molar tooth sign" on brain imaging. The purpose of this study was to identify potential mutations in a Chinese patient with Joubert syndrome by targeted massively parallel sequencing. Taking advantage of high-throughput DNA sequencing technologies, 18 Joubert-causing genes of a Chinese patient with classic Joubert syndrome were sequenced at a time, and 2 novel variants in the CEP290 gene (c.7323-7327delAGAAG and c.6012-2A>G) were identified in this patient. Sanger validation showed that 2 variants were inherited from each parents, respectively. Both variants are located in the C-terminal region of the CEP290 protein and are predicted to be deleterious. The results support that the combination of targeted genes enrichment and next-generation sequencing is valuable molecular diagnostic tool and suitable for clinical application. © The Author(s) 2014. Source
Tyler-Smith C.,Wellcome Trust Sanger Institute |
Yang H.,BGI Shenzen |
Yang H.,James D Watson Institute Of Genome Science |
Landweber L.F.,Princeton University |
And 6 more authors.
PLoS Biology | Year: 2015
The last few decades have utterly transformed genetics and genomics, but what might the next ten years bring? PLOS Biology asked eight leaders spanning a range of related areas to give us their predictions. Without exception, the predictions are for more data on a massive scale and of more diverse types. All are optimistic and predict enormous positive impact on scientific understanding, while a recurring theme is the benefit of such data for the transformation and personalization of medicine. Several also point out that the biggest changes will very likely be those that we don’t foresee, even now. © 2015 Tyler-Smith et al. Source
Wang Z.,BGI Shenzen |
Hobson N.,University of Alberta |
Galindo L.,University of Alberta |
Zhu S.,BGI Shenzen |
And 23 more authors.
Plant Journal | Year: 2012
Flax (Linum usitatissimum) is an ancient crop that is widely cultivated as a source of fiber, oil and medicinally relevant compounds. To accelerate crop improvement, we performed whole-genome shotgun sequencing of the nuclear genome of flax. Seven paired-end libraries ranging in size from 300 bp to 10 kb were sequenced using an Illumina genome analyzer. A de novo assembly, comprised exclusively of deep-coverage (approximately 94× raw, approximately 69× filtered) short-sequence reads (44-100 bp), produced a set of scaffolds with N50 = 694 kb, including contigs with N50 = 20.1 kb. The contig assembly contained 302 Mb of non-redundant sequence representing an estimated 81% genome coverage. Up to 96% of published flax ESTs aligned to the whole-genome shotgun scaffolds. However, comparisons with independently sequenced BACs and fosmids showed some mis-assembly of regions at the genome scale. A total of 43 384 protein-coding genes were predicted in the whole-genome shotgun assembly, and up to 93% of published flax ESTs, and 86% of A. thaliana genes aligned to these predicted genes, indicating excellent coverage and accuracy at the gene level. Analysis of the synonymous substitution rates (Ks) observed within duplicate gene pairs was consistent with a recent (5-9 MYA) whole-genome duplication in flax. Within the predicted proteome, we observed enrichment of many conserved domains (Pfam-A) that may contribute to the unique properties of this crop, including agglutinin proteins. Together these results show that de novo assembly, based solely on whole-genome shotgun short-sequence reads, is an efficient means of obtaining nearly complete genome sequence information for some plant species. © 2012 Blackwell Publishing Ltd. Source