Integrated Analysis of Whole Exome Sequencing and Copy Number Evaluation in Parkinson’s Disease

Abstract Early-onset Parkinson’s disease (EOPD) is usually caused by genetic variants and patients with EOPD develop symptoms before the age of 50, accounting for 5% Parkinson’s disease (PD). Here we present a Chinese Han pedigree with clinical features of EOPD. To determine the diagnosis and pathogenic mutations of this pedigree, whole exome sequencing, Sanger sequencing and real-time quantitative PCR were performed to detect all the four family members. Our results showed that a new form of compound heterozygous mutation in the PRKN gene, consisting of heterozygous point mutation c.850G > C (p.G284R) along with exon 4 deletion, is the causative genetic factor for EOPD in this pedigree. These discoveries may have implications for genetic counseling, clinical management and developing PRKN target gene therapy strategy.

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Whole-exome sequencing of 228 patients with sporadic Parkinson’s disease

Scientific Reports ◽

10.1038/srep41188 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 15

Author(s):

Cynthia Sandor ◽

Frantisek Honti ◽

Wilfried Haerty ◽

Konrad Szewczyk-Krolikowski ◽

Paul Tomlinson ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome ◽

Sporadic Parkinson’S Disease

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Whole-Exome Sequencing in Searching for New Variants Associated With the Development of Parkinson’s Disease

Frontiers in Aging Neuroscience ◽

10.3389/fnagi.2018.00136 ◽

2018 ◽

Vol 10 ◽

Cited By ~ 8

Author(s):

Marina V. Shulskaya ◽

Anelya Kh. Alieva ◽

Ivan N. Vlasov ◽

Vladimir V. Zyrin ◽

Ekaterina Yu. Fedotova ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Whole Exome

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inCNV: An Integrated Analysis Tool for Copy Number Variation on Whole Exome Sequencing

Evolutionary Bioinformatics ◽

10.1177/1176934320956577 ◽

2020 ◽

Vol 16 ◽

pp. 117693432095657

Author(s):

Saowwapark Chanwigoon ◽

Sakkayaphab Piwluang ◽

Duangdao Wichadakul

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Copy Number ◽

De Novo ◽

Mendelian Inheritance ◽

Copy Number Variations ◽

Integrated Analysis ◽

Analysis Tool ◽

Ensembl Database ◽

Whole Exome

The detection of copy number variations (CNVs) on whole-exome sequencing (WES) represents a cost-effective technique for the study of genetic variants. This approach, however, has encountered an obstacle with high false-positive rates due to biases from exome sequencing capture kits and GC contents. Although plenty of CNV detection tools have been developed, they do not perform well with all types of CNVs. In addition, most tools lack features of genetic annotation, CNV visualization, and flexible installation, requiring users to put much effort into CNV interpretation. Here, we present “inCNV,” a web-based application that can accept multiple CNV-tool results, then integrate and prioritize them with user-friendly interfaces. This application helps users analyze the importance of called CNVs by generating CNV annotations from Ensembl, Database of Genomic Variants (DGV), ClinVar, and Online Mendelian Inheritance in Man (OMIM). Moreover, users can select and export CNVs of interest including their flanking sequences for primer design and experimental verification. We demonstrated how inCNV could help users filter and narrow down the called CNVs to a potentially novel CNV, a common CNV within a group of samples of the same disease, or a de novo CNV of a sample within the same family. Besides, we have provided in CNV as a docker image for ease of installation ( https://github.com/saowwapark/inCNV ).

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Whole-exome sequencing in early-onset Parkinson's disease among ethnic Chinese

Neurobiology of Aging ◽

10.1016/j.neurobiolaging.2019.12.023 ◽

2020 ◽

Vol 90 ◽

pp. 150.e5-150.e11 ◽

Cited By ~ 4

Author(s):

Nannan Li ◽

Ling Wang ◽

Jinhong Zhang ◽

Eng-King Tan ◽

Junying Li ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Early Onset ◽

Ethnic Chinese ◽

Whole Exome ◽

Early Onset Parkinson’S Disease

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Integrated analysis of whole-exome sequencing and transcriptome profiling in males with autism spectrum disorders

Molecular Autism ◽

10.1186/s13229-015-0017-0 ◽

2015 ◽

Vol 6 (1) ◽

Cited By ~ 70

Author(s):

Marta Codina-Solà ◽

Benjamín Rodríguez-Santiago ◽

Aïda Homs ◽

Javier Santoyo ◽

Maria Rigau ◽

...

Keyword(s):

Autism Spectrum Disorders ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Transcriptome Profiling ◽

Autism Spectrum ◽

Integrated Analysis ◽

Whole Exome ◽

Spectrum Disorders

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Whole-exome sequencing reveals potential germline and somatic mutations in 60 malignant ovarian germ cell tumors

Biology of Reproduction ◽

10.1093/biolre/ioab052 ◽

2021 ◽

Author(s):

Juan Chen ◽

Yan Li ◽

Jianlei Wu ◽

Yakun Liu ◽

Shan Kang

Keyword(s):

Germ Cell ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Peripheral Blood ◽

Copy Number ◽

Somatic Mutations ◽

Germ Cell Tumors ◽

Germline Mutations ◽

Deletion Region ◽

Whole Exome

Abstract Background Malignant ovarian germ cell tumors (MOGCTs) are rare and heterogeneous ovary tumors. We aimed to identify potential germline mutations and somatic mutations in MOGCTs by whole-exome sequencing. Methods The peripheral blood and tumor samples from these patients were used to identify germline mutations and somatic mutations, respectively. For those genes corresponding to copy number alterations (CNA) deletion and duplication region, functional annotation of was performed. Immunohistochemistry was performed to evaluate the expression of mutated genes corresponding to CNA deletion region. Results In peripheral blood, copy number loss and gain were mostly found in yolk sac tumors (YST). Moreover, POU5F1 was the most significant mutated gene with mutation frequency > 10% in both CNA deletion and duplication region. In addition, strong cytoplasm staining of POU5F1 (corresponding to CNA deletion region) was found in 2 YST and nuclear staining in 2 dysgerminomas (DG) tumor samples. Genes corresponding to CNA deletion region were significantly enriched in the signaling pathway of regulating pluripotency of stem cells. In addition, genes corresponding to CNA duplication region were significantly enriched in the signaling pathways of RIG-I-like receptor, Toll-like receptor, NF-kappa B and Jak–STAT. KRT4, RPL14, PCSK6, PABPC3 and SARM1 mutations were detected in both peripheral blood and tumor samples. Conclusions Identification of potential germline mutations and somatic mutations in MOGCTs may provide a new field in understanding the genetic feature of the rare biological tumor type in the ovary.

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

Cancer Informatics ◽

10.4137/cin.s36612 ◽

2016 ◽

Vol 15 ◽

pp. CIN.S36612 ◽

Cited By ~ 3

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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