scholarly journals Whole Exome Sequencing Identifies genetic variants in Chinese Han pregnant women with Venous thromboembolism-a case control study

2020 ◽  
Author(s):  
Yupei Shen ◽  
Yan Zhang ◽  
Ying Xiong ◽  
Zhiping Zhang ◽  
Baohua Zhang ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Pregnant Women ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Large Scale ◽  
Single Nucleotide Variants ◽  
Chinese Han ◽  
Whole Exome ◽  
Increased Risk

Abstract Background: Venous thromboembolism (VTE) is a common health problem, causing considerable morbidity and mortality. The incidence of VTE is higher in pregnant women than in those who are not pregnant. However, genetic factors for VTE in pregnant women are largely unknown.Methods: We performed a large-scale prospective cohort study of 65138 pregnancies. Pregnant patients with VTE and pregnant women without VTE were enrolled in the study and sequenced by whole exome sequencing. Functional and enrichment analyses were performed using the DAVID online database. The protein-protein interaction network was constructed using the STRING database. Results: 5810 significant variants were associated with pregnant patients with VTE, including 4874 single nucleotide variants and 936 short deletions which were annotated in 3417 genes (P < 0.05). Fifty-six variants annotated in 46 genes (P < 0.001) and the top 3 variants, including rs2706258 (RNA LOC102724050, p = 1.25 × 10-6), rs17057520 (SCARA3, p = 4.64 × 10-5), and rs3739550 (CAAP1, p = 4.64 × 10-5), were identified. Fourteen low frequency variants had a minor allele frequency (MAF) of less than 1%. Logistic analysis revealed that rs7099478 (GRK5), rs8041208 (WDR72), rs17215792 (KLF7), rs13035688 (KLF7), rs6725221 (KLF7), and rs3214417 (KLF7) were associated with an increased risk of developing VTE (P < 0.05, OR > 1). In addition, combined pathway and PPI analyses revealed that CDC7 and MCM6 involved with DNA replication were associated with VTE in pregnant individuals.Conclusion: The study identified a series of variants and genes that may contribute to VTE in the Chinese pregnant population. Several genes may be risk factors for VTE including KLF7, GRK5, and WDR72. CDC7 and MCM6 may be related to the potential functions of VTE in pregnant women. Notably, the KLF7 gene had 4 genetic variants that were found to be associated with lipid metabolism and cardiovascular diseases. Therefore, further validation is required to reveal the KLF7 mechanism in pregnant women with VTE.

scholarly journals Whole-exome sequencing reveals genetic variants in ERC1 and KCNG4 associated with complete hydatidiform mole in Chinese Han women

Oncotarget ◽  
2017 ◽  
Vol 8 (43) ◽  
pp. 75264-75271
Author(s):  
Yan Yu ◽  
Bingjian Lu ◽  
Weiguo Lu ◽  
Shuang Li ◽  
Xiuqin Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Hydatidiform Mole ◽  
Complete Hydatidiform Mole ◽  
Chinese Han ◽  
Whole Exome

scholarly journals Whole-exome sequencing in evaluation of patients with venous thromboembolism

2017 ◽  
Vol 1 (16) ◽  
pp. 1224-1237 ◽  
Author(s):  
Eun-Ju Lee ◽  
Daniel J. Dykas ◽  
Andrew D. Leavitt ◽  
Rodney M. Camire ◽  
Eduard Ebberink ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Key Points

Key Points Using WES, we designed an extended thrombophilia panel consisting of 55 genes of significance to thrombosis. The extended thrombophilia panel identified multiple novel genetic variants with predicted roles in thrombosis or thrombophilia.

scholarly journals A domestic cat whole exome sequencing resource for trait discovery

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alana R. Rodney ◽  
Reuben M. Buckley ◽  
Robert S. Fulton ◽  
Catrina Fronick ◽  
Todd Richmond ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Diseases ◽  
Domestic Cat ◽  
Whole Genome Sequence ◽  
Exome Capture ◽  
Single Nucleotide Variants ◽  
Whole Exome ◽  
Olfactory Receptor Genes ◽  
Feline Model

AbstractOver 94 million domestic cats are susceptible to cancers and other common and rare diseases. Whole exome sequencing (WES) is a proven strategy to study these disease-causing variants. Presented is a 35.7 Mb exome capture design based on the annotated Felis_catus_9.0 genome assembly, covering 201,683 regions of the cat genome. Whole exome sequencing was conducted on 41 cats with known and unknown genetic diseases and traits, of which ten cats had matching whole genome sequence (WGS) data available, used to validate WES performance. At 80 × mean exome depth of coverage, 96.4% of on-target base coverage had a sequencing depth > 20-fold, while over 98% of single nucleotide variants (SNVs) identified by WGS were also identified by WES. Platform-specific SNVs were restricted to sex chromosomes and a small number of olfactory receptor genes. Within the 41 cats, we identified 31 previously known causal variants and discovered new gene candidate variants, including novel missense variance for polycystic kidney disease and atrichia in the Peterbald cat. These results show the utility of WES to identify novel gene candidate alleles for diseases and traits for the first time in a feline model.

scholarly journals Analysis workflow to assess de novo genetic variants from human whole-exome sequencing

2021 ◽  
Vol 2 (1) ◽  
pp. 100383
Author(s):  
Nicholas S. Diab ◽  
Spencer King ◽  
Weilai Dong ◽  
Garrett Allington ◽  
Amar Sheth ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
De Novo ◽  
Whole Exome ◽  
Analysis Workflow

scholarly journals Identification of rare genetic variants in Juvenile Idiopathic Arthritis using whole exome sequencing

2015 ◽  
Vol 13 (S1) ◽  
Author(s):  
E Sanchez ◽  
S Grandemange ◽  
F Tran Mau-Them ◽  
P Louis-Plence ◽  
A Carbasse ◽  
...  
Keyword(s):  
Juvenile Idiopathic Arthritis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Variants ◽  
Whole Exome ◽  
Rare Genetic Variants

scholarly journals High-Frequency Exon Deletion of DNA Cross-Link Repair 1C Accounting for Severe Combined Immunodeficiency May Be Missed by Whole-Exome Sequencing

2021 ◽  
Vol 12 ◽  
Author(s):  
Feifan Xiao ◽  
Yulan Lu ◽  
Bingbing Wu ◽  
Bo Liu ◽  
Gang Li ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Rare Variant ◽  
Severe Combined Immunodeficiency ◽  
Cell Receptor ◽  
Homozygous Deletion ◽  
Combined Immunodeficiency ◽  
Cross Link ◽  
Single Nucleotide Variants ◽  
Whole Exome

Next-generation sequencing (NGS) has been used to detect severe combined immunodeficiency (SCID) in patients, and some patients with DNA cross-link repair 1C (DCLRE1C) variants have been identified. Moreover, some compound variants, such as copy number variants (CNV) and single nucleotide variants (SNV), have been reported. The purpose of this study was to expand the genetic data related to patients with SCID carrying the compound DCLRE1C variant. Whole-exome sequencing (WES) was performed for genetic analysis, and variants were verified by performing Sanger sequencing or quantitative PCR. Moreover, we searched PubMed and summarized the data of the reported variants. Four SCID patients with DCLRE1C variants were identified in this study. WES revealed a homozygous deletion in the DCLRE1C gene from exons 1–5 in patient 1, exons 1–3 deletion and a novel rare variant (c.92T&gt;C, p.L31P) in patient 2, exons 1–3 deletion and a novel rare variant (c.328C&gt;G, p.L110V) in patient 3, and exons 1–4 deletion and a novel frameshift variant (c.449dup, p.His151Alafs*20) in patient 4. Based on literature review, exons 1–3 was recognized as a hotspot region for deletion variation. Moreover, we found that compound variations (CNV + SNV) accounted for approximately 7% variations in all variants. When patients are screened for T-cell receptor excision circles (TRECs), NGS can be used to expand genetic testing. Deletion of the DCLRE1C gene should not be ignored when a variant has been found in patients with SCID.

Whole Exome Sequencing of Six Chinese Families With Hereditary Non-Syndromic Hearing Loss: A Genetic Etiology Study

2020 ◽  
Author(s):  
Pengfei Liang ◽  
Fengping Chen ◽  
Shujuan Wang ◽  
Qiong Li ◽  
Wei Li ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Sanger Sequencing ◽  
Large Scale ◽  
Autosomal Recessive ◽  
Autosomal Recessive Inheritance ◽  
Chinese Families ◽  
Whole Exome ◽  
Syndromic Hearing Loss

Abstract Background: Hereditary non-syndromic hearing loss (NSHL) has a high genetic heterogeneity with >152 genes identified as associated molecular causes. The present study aimed to detect the possible damaging variants of the deaf probands from six unrelated Chinese families.Methods: After excluding the mutations in the most common genes, GJB2 and SLC26A4, 12 probands with prelingual deafness and autosomal recessive inheritance were evaluated by whole-exome sequencing (WES). All the candidate variants were verified by Sanger sequencing in all patients and their parents.Results: Biallelic mutations were identified in all deaf patients. Among these six families, 10 potentially causative mutations, including 3 reported and 7 novel mutations, in 3 different deafness-associated autosomal recessive (DFNB) genes (MYO15A, COL11A2, and CDH23) were identified. The mutations in MYO15A were frequent with 7/10 candidate variants. Sanger sequencing confirmed that these mutations segregated with the hearing loss of each family.Conclusions: Next-generation sequencing (NGS) approach becomes more cost-effective and efficient when analyzing large-scale genes compared to the conventional polymerase chain reaction-based Sanger sequencing, which is often used to screen common deafness-related genes. The current findings further extend the mutation spectrum of hearing loss in the Chinese population, which has a positive significance for genetic counseling.

scholarly journals RefCNV: Identification of Gene-Based Copy Number Variants Using Whole Exome Sequencing

2016 ◽  
Vol 15 ◽  
pp. CIN.S36612 ◽  
Author(s):  
Lun-Ching Chang ◽  
Biswajit Das ◽  
Chih-Jian Lih ◽  
Han Si ◽  
Corinne E. Camalier ◽  
...  
Keyword(s):  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Estimation Methods ◽  
Single Nucleotide Variants ◽  
False Positive Error ◽  
Reference Set ◽  
Genome Wide ◽  
Whole Exome

With rapid advances in DNA sequencing technologies, whole exome sequencing (WES) has become a popular approach for detecting somatic mutations in oncology studies. The initial intent of WES was to characterize single nucleotide variants, but it was observed that the number of sequencing reads that mapped to a genomic region correlated with the DNA copy number variants (CNVs). We propose a method RefCNV that uses a reference set to estimate the distribution of the coverage for each exon. The construction of the reference set includes an evaluation of the sources of variability in the coverage distribution. We observed that the processing steps had an impact on the coverage distribution. For each exon, we compared the observed coverage with the expected normal coverage. Thresholds for determining CNVs were selected to control the false-positive error rate. RefCNV prediction correlated significantly ( r = 0.96–0.86) with CNV measured by digital polymerase chain reaction for MET (7q31), EGFR (7p12), or ERBB2 (17q12) in 13 tumor cell lines. The genome-wide CNV analysis showed a good overall correlation (Spearman's coefficient = 0.82) between RefCNV estimation and publicly available CNV data in Cancer Cell Line Encyclopedia. RefCNV also showed better performance than three other CNV estimation methods in genome-wide CNV analysis.

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