Application Value of Whole Exome Sequencing in Screening and Identifying Pathogenic Genes of Hypopharyngeal Carcinoma

Abstract Background: Whole-exome sequencing has been used in many cancer research, but it is rarely used in Hypopharyngeal carcinoma. In our research, we performed whole-exome sequencing of DNA from 10 tumor tissue specimens from patients with hypopharyngeal cancer rather than targeted sequencing of specific genes.Methods: Whole-exome sequencing in 10 patients with hypopharyngeal carcinoma was performed to identify single nucleotide variations (SNVs) and insertions and deletions (INDELs). American College of Medical Genetics and Genomics (ACMG) guidelines were used to evaluate the pathogenicity of the selected variants. Gene Ontology (GO) and pathway enrichment were used to analyze the function and effect of mutated genes. Protein protein interaction (PPI) was analyzed by string online software.Results: 8113 mutation sites in 5326 genes were identified after strict screening. MEGF8, ITPR1, DYSF, DNAH10, CUL7, MYH14, LRP1, ASTN1, TTN, ASH1L, MYH11, KMT2C were mutated in more than 6 patients. We identified 72 pathogenic or potentially pathogenic mutations in 53 genes according to the ACMG guidelines. GO annotation and KEGG enrichment analysis show the possible effect of these pathogenic genes on cancer. Conclusion: We identified novel mutations in patients with hypopharyngeal cancer, and provided a foundation for future research on the pathogenesis of hypopharyngeal carcinoma and targeted treatment of hypopharyngeal carcinoma.

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Identification of candidate genes and pathways in retinopathy of prematurity by whole exome sequencing of preterm infants enriched in phenotypic extremes

Scientific Reports ◽

10.1038/s41598-021-83552-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Sang Jin Kim ◽

◽

Kemal Sonmez ◽

Ryan Swan ◽

J. Peter Campbell ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Preterm Infants ◽

Premature Infants ◽

Retinopathy Of Prematurity ◽

Smooth Endoplasmic Reticulum ◽

Enrichment Analysis ◽

Retinal Disease ◽

Gene Set Enrichment Analysis ◽

Whole Exome

AbstractRetinopathy of prematurity (ROP) is a vasoproliferative retinal disease affecting premature infants. In addition to prematurity itself and oxygen treatment, genetic factors have been suggested to predispose to ROP. We aimed to identify potentially pathogenic genes and biological pathways associated with ROP by analyzing variants from whole exome sequencing (WES) data of premature infants. As part of a multicenter ROP cohort study, 100 non-Hispanic Caucasian preterm infants enriched in phenotypic extremes were subjected to WES. Gene-based testing was done on coding nonsynonymous variants. Genes showing enrichment of qualifying variants in severe ROP compared to mild or no ROP from gene-based tests with adjustment for gestational age and birth weight were selected for gene set enrichment analysis (GSEA). Mean BW of included infants with pre-plus, type-1 or type 2 ROP including aggressive posterior ROP (n = 58) and mild or no ROP (n = 42) were 744 g and 995 g, respectively. No single genes reached genome-wide significance that could account for a severe phenotype. GSEA identified two significantly associated pathways (smooth endoplasmic reticulum and vitamin C metabolism) after correction for multiple tests. WES of premature infants revealed potential pathways that may be important in the pathogenesis of ROP and in further genetic studies.

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Screening of Candidate Pathogenic Genes for Spontaneous Abortion using Whole Exome Sequencing

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207324666210628115715 ◽

2021 ◽

Vol 24 ◽

Author(s):

Qingwen Zhu ◽

Yiwen Zhou ◽

Jiayi Ding ◽

Li Chen ◽

Jia Liu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Spontaneous Abortion ◽

Gene Fusion ◽

High Throughput Sequencing ◽

Kegg Pathway ◽

Novel Mutation ◽

Common Disease ◽

Pathogenic Genes ◽

Whole Exome

Background: Spontaneous abortion is a common disease in obstetrics and reproduction. Objective: This study aimed to screen candidate pathogenic genes for spontaneous abortion using whole-exome sequencing. Methods: Genomic DNA was extracted from abortion tissues of spontaneous abortion patients and sequenced using the Illumina HiSeq2500 high-throughput sequencing platform. Whole exome sequencing was performed to select harmful mutations, including SNP and insertion and deletion sites, associated with spontaneous abortion. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene fusion analyses were performed. MUC3A and PDE4DIP were two novel mutation genes that were screened and verified by PCR in abortion tissues of patients. Results: A total of 83,633 SNPs and 13,635 Indel mutations were detected, of which 29172 SNPs and 3093 Indels were screened as harmful mutations. The 7 GO-BP, 4 GO-CC, 9 GO-MF progress, and 3 KEGG pathways were enriched in GO and KEGG pathway analyses. A total of 746 gene fusion mutations were obtained, involving 492 genes. MUC3A and PDE4DIP were used for PCR verification because of their high number of mutation sites in all samples. Conclusion: There are extensive SNPs and Indel mutations in the genome of spontaneous abortion tissues, and the effect of these gene mutations on spontaneous abortion needs further experimental verification.

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Investigation of Pathogenic Genes in Peri-Implantitis from Implant Clustering Failure Patients: A Whole-Exome Sequencing Pilot Study

PLoS ONE ◽

10.1371/journal.pone.0099360 ◽

2014 ◽

Vol 9 (6) ◽

pp. e99360 ◽

Cited By ~ 8

Author(s):

Soohyung Lee ◽

Ji-Young Kim ◽

Jihye Hwang ◽

Sanguk Kim ◽

Jae-Hoon Lee ◽

...

Keyword(s):

Pilot Study ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Pathogenic Genes ◽

Whole Exome

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MO029CLINICAL CHARACTERISTICS AND PATHOGENIC GENES OF CONGENITAL SOLITARY KIDNEY WITH REPRODUCTIVE SYSTEM MALFORMATION*

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfab080.001 ◽

2021 ◽

Vol 36 (Supplement_1) ◽

Author(s):

Rongrong HU ◽

Lubin Xu ◽

Minting Chen ◽

Na Chen ◽

Tiantian Ma ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Reproductive System ◽

Solitary Kidney ◽

Imaging Features ◽

Mrkh Syndrome ◽

Pathogenic Genes ◽

Whole Exome ◽

Genital Malformation ◽

Congenital Solitary Kidney

Abstract Background and Aims Congenital solitary kidney – one category of congenital anomalies of the kidney and urinary tract (CAKUT) may combine with other system malformations such as reproductive, cardiac, skeletal system, and so on. Our study analysed the clinical characteristics among congenital solitary kidney patients and their reproductive system malformations. And further work about probable pathogenic genes was explored. Method The information of CAKUT patients who were indicated by Doppler ultrasound was collected. The clinical and imaging features including reproductive system abnormalities were retrospectively reviewed in patients with congenital solitary kidney. In patients with Mayer-Rokitansky- Küster-Hauser (MRKH) syndrome, a disorder of congenital agenesis of uterus and vagina, whole exome sequencing was performed. Rare variants in CAKUT-related genes were analysed. Trio analysis was conducted to identify de novo mutations. Results We identified 209 patients with congenital solitary kidney from July 20, 2017 to July 19, 2020 among 1160 CAKUT patients in Peking Union Medical College Hospital. There were 152 females. The average age of congenital solitary kidney patients was 35.26±18.42 years when they were diagnosed. 53.2% showed different degrees of proteinuria and hematuria. Serum creatinine elevating was proved 13.1% and 40% in women and men separately. Among 81 females who also had a gynecological ultrasound report, 88.9% combined with genital malformation, oblique vaginal septum syndrome 48.7%, the Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome 22.2%, malformed uterus 23.5%, vaginal atresia and other genital malformation 7%. Congenital heart disease, complete transposition of viscera, and scoliosis were also found in some patients with congenital solitary kidney. Furthermore, based on the whole exome data of 443 patients with MRKH syndrome, seven function-lost mutations were confirmed. And also two De nove mutations (NOTCH2 (NM_024408.3: c.703A>T(p.Thr235Ser), ESRRG (NM_001243512.1:c.-169-8delT)), one homozygous patients with parents heterozygous (NM_133433.3:c.8084C>T(p.Thr2695Me) were identified as possible pathogenic genes caused CAKUT. Conclusion We should be aware of reproductive system malformations in CAKUT patients. Whole exome sequencing may suggest common pathogenic genes between the two kinds of diseases.

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Whole-exome sequencing identifies a Novel SCN5A mutation (C335R) in a Chinese family with arrhythmia

Cardiology in the Young ◽

10.1017/s1047951117002980 ◽

2018 ◽

Vol 28 (5) ◽

pp. 688-691 ◽

Cited By ~ 2

Author(s):

Hao Huang ◽

Dong-Bo Ding ◽

Liang-Liang Fan ◽

Jie-Yuan Jin ◽

Jing-Jing Li ◽

...

Keyword(s):

Exome Sequencing ◽

Missense Mutation ◽

Whole Exome Sequencing ◽

Chinese Family ◽

Illumina Hiseq ◽

Α Subunit ◽

Pathogenic Genes ◽

Whole Exome ◽

Gene Filtering ◽

Protein Dysfunction

AbstractBackgroundSCN5A encodes sodium-channel α-subunit Nav1.5. The mutations of SCN5A can lead to hereditary cardiac arrhythmias such as the long-QT syndrome type 3 and Brugada syndrome. Here we sought to identify novel mutations in a family with arrhythmia.MethodsGenomic DNA was isolated from blood of the proband, who was diagnosed with atrial flutter. Illumina Hiseq 2000 whole-exome sequencing was performed and an arrhythmia-related gene-filtering strategy was used to analyse the pathogenic genes. Sanger sequencing was applied to verify the mutation co-segregated in the family.Results and conclusionsA novel missense mutation in SCN5A (C335R) was identified, and this mutation co-segregated within the affected family members. This missense mutation was predicted to result in amplitude reduction in peak Na+ current, further leading to channel protein dysfunction. Our study expands the spectrum of SCN5A mutations and contributes to genetic counselling of families with arrhythmia.

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Whole-exome sequencing for detecting inborn errors of immunity: overview and perspectives

F1000Research ◽

10.12688/f1000research.12365.1 ◽

2017 ◽

Vol 6 ◽

pp. 2056

Author(s):

Barbara Bosch ◽

Yuval Itan ◽

Isabelle Meyts

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Molecular Mechanisms ◽

Future Research ◽

Sequencing Analysis ◽

Genetic Etiology ◽

Inborn Errors ◽

Inborn Errors Of Immunity ◽

Whole Exome ◽

Clinical Description

The study of inborn errors of immunity is based on a comprehensive clinical description of the patient’s phenotype and the elucidation of the underlying molecular mechanisms and their genetic etiology. Deciphering the pathogenesis is key to genetic counseling and the development of targeted therapy. This review shows the power of whole-exome sequencing in detecting inborn errors of immunity along five central steps taken in whole-exome sequencing analysis. In parallel, we highlight the challenges for the clinical and scientific use of the method and how these hurdles are currently being addressed. We end by ruminating on major areas in the field open to future research.

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99-Case Study of Sporadic Aortic Dissection by Whole Exome Sequencing Indicated Novel Disease-Associated Genes and Variants in Chinese Population

BioMed Research International ◽

10.1155/2020/7857043 ◽

2020 ◽

Vol 2020 ◽

pp. 1-12

Author(s):

Zanxin Wang ◽

Xianmian Zhuang ◽

Bailang Chen ◽

Junmin Wen ◽

Fang Peng ◽

...

Keyword(s):

Correlation Analysis ◽

Aortic Dissection ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Chinese Population ◽

Enrichment Analysis ◽

Copy Number Variations ◽

Nucleotide Polymorphisms ◽

Pathogenic Variants ◽

Whole Exome

Background. In this study, the whole exome sequencing in human aortic dissection, a highly lethal cardiovascular disease, was investigated to explore the aortic dissection-associated genes and variants in Chinese population. Methods. Whole exome sequencing was performed in 99 cases of aortic dissection. All single nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and copy number variations (CNVs) were filtered to exclude the benign variants. Enrichment analysis and disease-gene correlation analysis were performed. Results. 3425873 SNPs, 685245 InDels, and 1177 CNVs were identified, and aortic dissection-associated SNPs, InDels, and CNVs were collected. After the disease correlation analysis, 20 candidate genes were identified. Part of these genes such as MYH11, FBN1, and ACTA2 were consistent with previous studies, while MLX, DAB2IP, EP300, ZFYVE9, PML, and PRKCD were newly identified as candidate aortic dissection-associated genes. Conclusion. The pathogenic and likely pathogenic variants in most of AD-associated genes (FBN1, MYH11, EFEMP2, TGFBR2, FBN2, COL3A1, and MYLK) were identified in our cohort study, and pathogenic CNVs involved in MYH11, COL family, and FBN were also identified which are not detectable by other NGS analysis. The correlation between MLX, DAB2IP, EP300, ZFYVE9, PML, PRKCD, and aortic dissection was identified, and EP300 may play a key role in AD.

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Integrative analyses identify potential key genes and pathways in Keshan disease using whole-exome sequencing

10.1101/2021.03.12.21253491 ◽

2021 ◽

Author(s):

Jichang Huang ◽

Chenqing Zheng ◽

Rong Luo ◽

Mingjiang Liu ◽

Qingquan Gu ◽

...

Keyword(s):

Network Analysis ◽

Exome Sequencing ◽

Candidate Genes ◽

Whole Exome Sequencing ◽

Heart Development ◽

Keshan Disease ◽

Pathway Enrichment Analysis ◽

Ppi Network ◽

Pathogenic Genes ◽

Whole Exome

AbstractKeshan disease (KD), an endemic heart disease with multifocal necrosis and replacement fibrosis of the myocardium,is still a nightmare situation for human health. However, molecular mechanism in the pathogenesis of KD remains unclear. Herein, blood samples were collected from 68 KD patients and 100 controls, and we systematically analyzed mutation profiles using whole-exome sequencing (WES). Causative genes of dilated cardiomyopathy (DCM), gene-based burden analysis, disease and pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed. Of the 98 DCM-causative genes, 106 rare variants in 28 genes were detected in KD patients with minor allele frequency (MAF) < 0.001. Gene-based burden analysis, PPI network analysis, and automated Phenolyzer analysis were performed to prioritize 199 candidate genes, which combined with 98 DCM-causative genes, and reference genes from gene microarray or proteomics in KD. Then, 19 candidate pathogenic genes were selected, and 9 candidate genes were identified using PPI analysis, including HIF1A, GART, ALAD, VCL, DTNA, NEXN, INPPL1, NOS3, and JAK2. The 199 candidate genes were further analyzed using disease enrichment with CTD database and PPI analysis, and 21 candidate genes were identified. By combining with disease enrichment and PPI analysis, 7 Selenium (Se)-related genes were further identified, including ALAD, RBM10, GSN, GGT1, ADD1, PARP1, and NOS3. Based on the gene function and data validation, NEXN, TAF1C, FUT4, ALAD, ZNF608, and STX2 were the most likely pathogenic genes in KD. Notably, ALAD is the only candidate pathogenic gene identified by four different analyses, and its homozygous mutant mice could affect heart development and cause death.

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Whole-exome sequencing reveals novel mutations and epigenetic regulation in hypopharyngeal carcinoma

Oncotarget ◽

10.18632/oncotarget.19674 ◽

2017 ◽

Vol 8 (49) ◽

pp. 85326-85340 ◽

Cited By ~ 4

Author(s):

Ping Wu ◽

Honglong Wu ◽

Yaoyun Tang ◽

Shi Luo ◽

Xing Fang ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Epigenetic Regulation ◽

Hypopharyngeal Carcinoma ◽

Novel Mutations ◽

Whole Exome

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Identification of the gene defect responsible for severe hypercholesterolaemia using whole-exome sequencing

Scientific Reports ◽

10.1038/srep11380 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 7

Author(s):

Li-Yuan Sun ◽

Yong-Biao Zhang ◽

Long Jiang ◽

Ning Wan ◽

Wen-Feng Wu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Genetic Type ◽

Chinese Patients ◽

Homozygous Mutation ◽

Cdna Sequencing ◽

Pathogenic Genes ◽

Whole Exome ◽

Pathogenic Gene

Abstract Familial hypercholesterolaemia (FH) is a serious genetic metabolic disease. We identified a specific family in which the proband had typical homozygous phenotype of FH, but couldn’t detect any mutations in usual pathogenic genes using traditional sequencing. This study is the first attempt to use whole exome sequencing (WES) to identify the pathogenic genes in Chinese FH. The routine examinations were performed on all parentage members and WES on 5 members. We used bioinformatics methods to splice and filter out the pathogenic gene. Finally, Sanger sequencing and cDNA sequencing were used to verify the candidate genes. Half of parentage members had got hypercholesterolaemia. WES identified LDLR IVS8[−10] as a candidate mutation from 222,267 variations. The Sanger sequencing showed proband had a homozygous mutation inherited from his parents and this loci were cosegregated with FH phenotype. The cDNA sequencing revealed that this mutations caused abnormal shearing. This mutation was first identified in Chinese patients and this homozygous mutation is a new genetic type of FH. This is the first time that WES was used in Chinese FH patients. We detected a novel genetic type of LDLR homozygous mutation. WES is powerful tools to identify specific FH families with potentially pathogenic gene mutations.

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