High resolution global chromosomal aberrations from spontaneous miscarriages revealed by low coverage whole genome sequencing

Qi, Hong; Xuan, Zhaoling; Du, Yang; Cai, Lirong; Zhang, Han; Kong, Xiangdong; Yang, Kai; Mi, Yang; Fu, Xinxin; Cao, Shanbo; Wang, Juan; Chen, Chongjian; Liang, Junbin

doi:10.1016/j.ejogrb.2018.03.008

Cited by 25 publications

(32 citation statements)

References 38 publications

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“…Each participant received counselling after NIPSCCD screening. Positive NIPSCCD individuals with trisomy 21, 18, and 13 were suggested to undergo invasive testing for prenatal diagnosis, while positive individuals with CNVs detected by NIPSCCD were validated by amniocentesis followed by whole‐genome sequencing (Qi et al, ) or telephone follow‐ups. All the negative ones were confirmed by telephone follow‐ups.…”

Section: Methodsmentioning

confidence: 99%

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Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low‐pass whole‐genome sequencing

Zhang

Han

et al. 2019

Molec Gen & Gen Med

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Background Expanding noninvasive prenatal testing (NIPT) to include the detection of fetal subchromosomal copy number variations (CNVs) significantly decreased the sensitivity and specificity. Developing analytic pipeline to achieve high performance in the noninvasive detection of CNVs will largely contribute to the application of CNVs screening in clinical practice. Methods We developed the Noninvasively Prenatal Subchromosomal Copy number variation Detection (NIPSCCD) method based on low‐pass whole‐genome sequencing, and evaluated its efficacy in detecting fetal CNVs and chromosomal aneuploidies with 20,003 pregnant women. Results Totally, NIPSCCD identified 36 CNVs, including 29 CNVs consistent and 7 CNVs inconsistent with amniocytes tests. Additionally, seven fetal CNVs identified by amniocytes testing were undetected by NIPSCCD. The sensitivities for detecting CNVs > 10 Mb, 5 Mb–10 Mb, and CNVs < 5 Mb were 91.67%, 100.00%, and 68.42%, respectively. Moreover, NIPSCCD identified 103/ true positive trisomy 21/18/13 cases and 21 false positives, producing an overall 100.00% sensitivity and 99.89% specificity. Conclusion NIPSCCD showed a good performance in detecting fetal subchromosomal CNVs, especially for CNVs >10 Mb, and can be incorporated into the routine NIPT chromosomal aneuploidies screening with high sensitivity and specificity.

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Section: Methodsmentioning

confidence: 99%

“…: A29319) according to the manufacture's instruction. Library construction, quality control, and sequencing were performed as previously described (Liang et al, ; Qi et al, ; Song et al, ). Briefly, 2.5 ng of cfDNA or fragmented DNA was used for the preparation of sequencing libraries.…”

Section: Methodsmentioning

confidence: 99%

Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low‐pass whole‐genome sequencing

Zhang

Han

et al. 2019

Molec Gen & Gen Med

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“…Up to date, the discovery of miscarriage-associated risk factors is still on the way. Current known risk factors include certain infections [7], endocrine disturbance [8], genital malformation [9], chromosome aberrations [10] and immune system disorder [11]. Recently, the relationship between inflammation and miscarriage has attracted more attention.…”

Section: Introductionmentioning

confidence: 99%

The benefits of higher LMR for early threatened abortion: A retrospective cohort study

Feng

Chen

et al. 2020

PLoS ONE

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To investigate the relation of inflammation-related parameters and pregnancy outcome in women with the early threatened abortion. Method of study 630 women with early threatened abortion were divided into two groups based on the pregnancy outcome. All of them had the blood routine examination before treating. The differences between two groups were analyzed by the Chi-squared test, Student T test, Mann-Whitney U test, Binary Logistic Regression, Marginal Structural Model and Threshold effect analysis. Results We found that there is no significant difference in the pregnancy outcome for NLR (OR:0.92, CI95%:0.72, 1.17) and PLR (OR:1.00, CI%:0.99, 1.01). However, a difference had a statistical significance in the pregnancy outcome when LMR less than 2.19 (OR:0.39, CI95%:0.19,0.82). Conclusions This study suggested that higher LMR was related to the lower risk of miscarriage in the women with early threatened abortion in a way.

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“…Low coverage whole‐genome sequencing was performed by Annoroad Genomics (Beijing, China) following the procedure previously described . Detection of CNVs was also performed as previously described …”

Section: Methodsmentioning

confidence: 99%

Sequence variant in the CDC42BPB gene is potentially associated with Mullerian duct anomalies

Luo

Feng

et al. 2020

J of Obstet and Gynaecol

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Aim: Mullerian duct anomalies (MDA) are common female genital tract malformations. Genetic and environmental factors are important causes of MDA in women. Although many genes and mutations have been found to be associated with the pathogenesis of MDA, in most cases, the genetic pathogenic factors of MDA are still unknown. Methods: We first analyzed the three sisters using low coverage whole-genome sequencing. Then wholeexome sequencing was carried out in each patient. The identified sequence variant was confirmed by Sanger sequencing. In silico pathogenicity analysis and conservative analysis of the mutation site were also performed. Protein structural modeling was used to analyze the effect of the mutated amino acid. Results: We first analyzed the three sisters with septate uterus using low coverage whole-genome sequencing, but no possible pathogenic copy number variation was found. Then whole-exome sequencing was performed on the three sisters, and a rare homozygous variant, CDC42BPB:c.2012G>A:p.R671Q, was identified. All three patients were found with this variant. Sanger sequencing validated that this variant was segregated within the family. In silico pathogenicity analysis and conservative analysis of the mutation site suggested that the variant might be damaging. Protein structural analysis suggested that R671Q might weaken the electrostatic potential of this region, which may be a significant regulation target or protein interaction surface of CDC42BPB. Conclusion: We demonstrated that CDC42BPB genetic variant might be potentially associated with the pathogenesis of MDA.

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High resolution global chromosomal aberrations from spontaneous miscarriages revealed by low coverage whole genome sequencing

Cited by 25 publications

References 38 publications

Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low‐pass whole‐genome sequencing

Noninvasive prenatal testing for fetal subchromosomal copy number variations and chromosomal aneuploidy by low‐pass whole‐genome sequencing

The benefits of higher LMR for early threatened abortion: A retrospective cohort study

Sequence variant in the CDC42BPB gene is potentially associated with Mullerian duct anomalies

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