scholarly journals Candidate Predisposition Variants in Kaposi Sarcoma as Detected by Whole-Genome Sequencing

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Sanni J Rinne ◽  
Lauri J Sipilä ◽  
Päivi Sulo ◽  
Emmanuelle Jouanguy ◽  
Vivien Béziat ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Kaposi Sarcoma ◽  
The Other ◽  
Whole Genome ◽  
Genome Wide ◽  
Starting Point ◽  
Familial Clustering ◽  
Iranian Family ◽  
Classic Kaposi Sarcoma

Abstract Familial clustering of classic Kaposi sarcoma (CKS) is rare with, approximately 100 families reported to date. We studied 2 consanguineous families, 1 Iranian and 1 Israeli, with multiple cases of adult CKS and without overt underlying immunodeficiency. We performed genome-wide linkage analysis and whole-genome sequencing to discover the putative genetic cause for predisposition. A 9-kb homozygous intronic deletion in RP11-259O2.1 in the Iranian family and 2 homozygous variants, 1 in SCUBE2 and the other in CDHR5, in the Israeli family were identified as possible candidates. The presented variants provide a robust starting point for validation in independent samples.

scholarly journals Whole-Genome Sequencing IdentifiesSTAT4as a Putative Susceptibility Gene in Classic Kaposi Sarcoma

2014 ◽  
Vol 211 (11) ◽  
pp. 1842-1851 ◽  
Author(s):  
Mervi Aavikko ◽  
Eevi Kaasinen ◽  
Janne K. Nieminen ◽  
Minji Byun ◽  
Iikki Donner ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Susceptibility Gene ◽  
Kaposi Sarcoma ◽  
Whole Genome ◽  
Classic Kaposi Sarcoma

scholarly journals Integration of genome wide association studies and whole genome sequencing provides novel insights into fat deposition in chicken

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Gabriel Costa Monteiro Moreira ◽  
Clarissa Boschiero ◽  
Aline Silva Mello Cesar ◽  
James M. Reecy ◽  
Thaís Fernanda Godoy ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Association Studies ◽  
Fat Deposition ◽  
Genome Wide Association ◽  
Genome Wide Association Studies ◽  
Whole Genome ◽  
Genome Wide

scholarly journals Detection and characterization of copy number variants based on whole-genome sequencing by DNBSEQ platforms

2019 ◽  
Author(s):  
Junhua Rao ◽  
Lihua Peng ◽  
Fang Chen ◽  
Hui Jiang ◽  
Chunyu Geng ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Copy Number ◽  
Copy Number Variants ◽  
Copy Number Variant ◽  
Whole Genome ◽  
Genome Wide ◽  
Wide Range ◽  
Distribution Sensitivity ◽  
Cnv Detection

AbstractBackgroundNext-generation sequence (NGS) has rapidly developed in past years which makes whole-genome sequencing (WGS) becoming a more cost- and time-efficient choice in wide range of biological researches. We usually focus on some variant detection via WGS data, such as detection of single nucleotide polymorphism (SNP), insertion and deletion (Indel) and copy number variant (CNV), which playing an important role in many human diseases. However, the feasibility of CNV detection based on WGS by DNBSEQ™ platforms was unclear. We systematically analysed the genome-wide CNV detection power of DNBSEQ™ platforms and Illumina platforms on NA12878 with five commonly used tools, respectively.ResultsDNBSEQ™ platforms showed stable ability to detect slighter more CNVs on genome-wide (average 1.24-fold than Illumina platforms). Then, CNVs based on DNBSEQ™ platforms and Illumina platforms were evaluated with two public benchmarks of NA12878, respectively. DNBSEQ™ and Illumina platforms showed similar sensitivities and precisions on both two benchmarks. Further, the difference between tools for CNV detection was analyzed, and indicated the selection of tool for CNV detection could affected the CNV performance, such as count, distribution, sensitivity and precision.ConclusionThe major contribution of this paper is providing a comprehensive guide for CNV detection based on WGS by DNBSEQ™ platforms for the first time.

BIOM-23. A PILOT STUDY OF WHOLE GENOME SEQUENCING (WGS) OF PLASMA CELL-FREE DNA (cfDNA) FOR ULTRASENSITIVE DETECTION OF TUMOR DNA IN PATIENTS WITH GLIOBLASTOMA (GBM)

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi15-vi15
Author(s):  
Stephen J Bagley ◽  
Jacob Till ◽  
Aseel Abdalla ◽  
MacLean Nasrallah ◽  
Tomer Lauterman ◽  
...  
Keyword(s):  
Pilot Study ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Tumor Tissue ◽  
Methylation Status ◽  
Tumor Burden ◽  
Whole Genome ◽  
Newly Diagnosed ◽  
Genome Wide ◽  
Tumor Dna

Abstract BACKGROUND Plasma circulating tumor DNA (ctDNA) is rarely detectable by traditional methods in patients with GBM. As a result, unlike in lung and other cancers, serial next generation sequencing of ctDNA for monitoring GBM tumor burden has been challenging. In light of the low tumor fraction (TF) of DNA fragments in GBM patient plasma and the urgent need to improve upon MRI for tracking GBM tumor burden, we conducted a pilot study in patients with newly diagnosed GBM using the C2 intelligence platform (C2i Genomics), which leverages genome-wide mutational integration for highly sensitive ctDNA detection. METHODS Plasma was collected pre- and post-operatively in patients with newly diagnosed GBM undergoing surgical resection/biopsy. cfDNA was extracted, quantified, and analyzed for fragment size. Genomic DNA (gDNA) was extracted from matched tumor tissue. Whole genome sequencing (WGS) was performed on both gDNA and cfDNA. A specific copy number alteration (CNA) compendium was created for each patient to generate a readout of TF (Zviran, Nat Medicine 2020). We assessed the association between TF at post-operative day 1 (a surrogate for residual disease) and OS, adjusting for other prognostic factors using Cox regression. RESULTS 37 patients were enrolled. For samples with high tumor fraction (n=5), a statistically significant (p< 1e-4) correlation between CNA profiles of tumor tissue and plasma samples was observed. Post-operative TF above the median value was associated with inferior OS (median 7.7 vs. 19.3 months, p=0.019). This association persisted after adjusting for age, O6-methylguanine-DNA methyltransferase methylation status, extent of resection, and performance status (adjusted HR 2.5, 95% CI 1.1-5.6, p=0.03). CONCLUSION Genome-wide mutational integration enables ultra-sensitive detection of ctDNA in GBM patient plasma. Post-operative TF measured by the C2i test is independently associated with OS in newly diagnosed GBM, providing the foundation to evaluate this technology for personalized prognostication and disease monitoring.

scholarly journals Fine Mapping Using Whole-Genome Sequencing Confirms Anti-Müllerian Hormone as a Major Gene for Sex Determination in Farmed Nile Tilapia (Oreochromis niloticus L.)

2019 ◽  
Vol 9 (10) ◽  
pp. 3213-3223 ◽  
Author(s):  
Giovanna Cáceres ◽  
María E. López ◽  
María I. Cádiz ◽  
Grazyella M. Yoshida ◽  
Ana Jedlicki ◽  
...  
Keyword(s):  
Sex Determination ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Oreochromis Niloticus ◽  
Nile Tilapia ◽  
Major Gene ◽  
Whole Genome ◽  
Important Species ◽  
Genome Wide ◽  
A Genome

Nile tilapia (Oreochromis niloticus) is one of the most cultivated and economically important species in world aquaculture. Intensive production promotes the use of monosex animals, due to an important dimorphism that favors male growth. Currently, the main mechanism to obtain all-male populations is the use of hormones in feeding during larval and fry phases. Identifying genomic regions associated with sex determination in Nile tilapia is a research topic of great interest. The objective of this study was to identify genomic variants associated with sex determination in three commercial populations of Nile tilapia. Whole-genome sequencing of 326 individuals was performed, and a total of 2.4 million high-quality bi-allelic single nucleotide polymorphisms (SNPs) were identified after quality control. A genome-wide association study (GWAS) was conducted to identify markers associated with the binary sex trait (males = 1; females = 0). A mixed logistic regression GWAS model was fitted and a genome-wide significant signal comprising 36 SNPs, spanning a genomic region of 536 kb in chromosome 23 was identified. Ten out of these 36 genetic variants intercept the anti-Müllerian (Amh) hormone gene. Other significant SNPs were located in the neighboring Amh gene region. This gene has been strongly associated with sex determination in several vertebrate species, playing an essential role in the differentiation of male and female reproductive tissue in early stages of development. This finding provides useful information to better understand the genetic mechanisms underlying sex determination in Nile tilapia.

DNA Sequencing of a Murine Acute Promyelocytic Leukemia (APL) Genome Using Next Generation Technology.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3965-3965
Author(s):  
Lukas D. Wartman ◽  
Li Ding ◽  
David E. Larson ◽  
Michael D. McLellan ◽  
Heather Schmidt ◽  
...  
Keyword(s):  
Mouse Model ◽  
Dna Sequencing ◽  
Whole Genome Sequencing ◽  
Acute Promyelocytic Leukemia ◽  
Genome Sequencing ◽  
Somatic Mutations ◽  
Promyelocytic Leukemia ◽  
The Other ◽  
Whole Genome ◽  
Base Pairs

Abstract Abstract 3965 Poster Board III-901 We have recently established that whole genome sequencing is a valid, unbiased approach that can identify novel candidate mutations that may be important for AML pathogenesis (Ley et al Nature 2008, Mardis et al NEJM 2009). Acute promyelocytic leukemia (APL, FAB M3 AML) is a subtype of AML characterized by the t(15;17)(q22;q11.2) translocation that creates an oncogenic fusion gene, PML-RARA. Our laboratory has previously modeled APL in a mouse in an effort to understand the genetic events that lead to the disease. In our knockin mouse model, a human PML-RARA cDNA was targeted to the 5' untranslated region of the mouse cathepsin G gene on chromosome 14 (mCG-PR). The targeting vector was transfected into the RW-4 embryonic stem cell line, derived from a 129/SvJ mouse. The transfected RW-4 cells were injected into C57Bl/6 blastocysts, and chimeric offspring were bred to C57Bl/6 mice. F1 129/SvJ x C57Bl/6 mice were subsequently backcrossed onto the B6/Taconic background for 10 generations before establishing a tumor watch. About 60% of the mCG-PR mice in the Bl/6 background develop a disease that closely resembles APL only after a latent period of 7-18 months, suggesting that additional progression mutations are required for APL development. Array-based genomic techniques (expression array studies and high resolution CGH) have revealed some recurring genetic alterations that may be relevant for progression (i.e. an interstitial deletion of chromosome 2, trisomy 15, etc.), but gene-specific progression mutations have not yet been identified. To begin to identify these mutations in an unbiased fashion, we sequenced a cytogenetically normal, diploid mouse APL genome using massively parallel DNA sequencing via the Illumina platform. Since the tumor arose in a highly inbred mouse strain, we predicted that 15x coverage of the genome (approximately 40 billion base pairs of sequence) would be necessary to identify >90% of the heterozygous somatic mutations. We generated 2 Illumina paired-end libraries (insert sizes of 300-350 bp and 550-600 bp) and generated 59.64 billion base pairs of sequence with 3 full sequencing runs; the reads that successfully mapped generated 15.6x coverage. The sequence data predicted 87,778 heterozygous Single Nucleotide Variants (SNVs) compared to the mouse C57Bl6/J reference sequence, and 23,439 homozygous SNVs. Of the predicted heterozygous SNVs, 695 were non-synonymous (missense or nonsense, or altering a canonical splice site). Thus far, 80 of these putative non-synonymous SNVs have been further analyzed using Sanger sequencing of the original tumor DNA vs. pooled B6/Taconic spleen DNA and pooled129/SvJ spleen DNA as controls. 37/80 were shown to be false positive calls, and 37 were inherited SNPs from residual regions of the129/SvJ genome. 6/80 were present only in the tumor genome, and were candidate somatic mutations. These 6 were screened in 89 additional murine APL tumor samples derived from the same mouse model. Mutations in the Jarid2 (L915I) and Capns2 (N149S) genes occurred only in the proband, and are therefore of uncertain significance. 4/6 mutations were found in additional samples; 3 of these mutations were derived from a common ancestor of the proband and the other affected mice, and were therefore not relevant for pathogenesis. The other recurring mutation was in the pseudokinase domain of JAK1 (V657F), and was identified in one other mouse that was not closely related to the proband. This mutation is orthologous to the known activating mutation V617F in human JAK2, and is identical to a recently described JAK1 pseudokinase domain mutation (V658F) found in human APL and T-ALL samples (EG Jeong et al, Clin Can Res 14: 3716, 2008). We are currently testing the functional significance of this mutation by expressing it in bone marrow cells derived from young WT vs. mCG-PR mice. In summary, unbiased whole genome sequencing of a mouse APL genome has identified a recurring mutation of JAK1 found in both human and mouse APL samples. This approach may allow us to rapidly identify progression mutations that are common to human and murine AML, and provides an important proof-of-concept that this mouse model of AML is functionally related to its human counterpart. Disclosures: No relevant conflicts of interest to declare.

Genome-wide DNA polymorphisms in eliteindicarice inbreds discovered by whole-genome sequencing

2012 ◽  
Vol 10 (6) ◽  
pp. 623-634 ◽  
Author(s):  
Gopala K. Subbaiyan ◽  
Daniel L. E. Waters ◽  
Sanjay K. Katiyar ◽  
Ajanahalli R. Sadananda ◽  
Satyadev Vaddadi ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Dna Polymorphisms ◽  
Whole Genome ◽  
Genome Wide
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