scholarly journals P.053 Whole-genome sequencing identified a frameshift mutation at LMNB1 in a family with early-onset dystonia

2019 ◽  
Vol 46 (s1) ◽  
pp. S28
Author(s):  
RK Yuen ◽  
B Adhami-Mojarad ◽  
I Backstrom ◽  
A Yin ◽  
T Soman
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Early Onset ◽  
Frameshift Mutation ◽  
Age Of Onset ◽  
Pathogenic Mutation ◽  
Whole Genome ◽  
Illumina Hiseq ◽  
Abnormal Movements ◽  
Generalized Dystonia

Background: Dystonia is a hyperkinetic condition that produces abnormal movements or postures. Its diagnostic procedure is often challenging and time consuming. Genetic testing provides an effective approach for diagnosis, but currently only very few dystonia genes have been identified. We propose that studying early-onset forms of dystonia with the use of whole-genome sequencing (WGS) will improve the identification of dystonia-relevant genes and mutations. Methods: We performed deep WGS using the Illumina HiSeq X technology in a mother-proband pair with dystonia. The mother has generalized dystonia (age of onset: 15) and the proband has myoclonic dystonia (age of onset: 11). Results: No pathogenic mutation was identified in any of the known dystonia genes. However, we identified a rare heterozygous frameshift mutation (p.K342fs*7) at LMNB1 that was shared between the mother and the proband. Duplication of LMNB1 is known to cause Adult-onset Demyelinating Leukodystrophy. A heterozygous deletion of LMNB1 has been reported in a patient with microcephaly and global developmental disorder. Conclusions: Further characterization of phenotypes in the participants and their family members is needed to confirm the relationship between mutation in LMNB1 and dystonia. This work provides a proof-of-principle that novel disease-relevant genes can potentially be identified using the proposed approach.

scholarly journals 799. Genetic Diversity of Mycobacterium tuberculosis Strains Causing Drug-Resistant Tuberculosis in Central Region of Mozambique: The Whole-Genome Sequencing

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S286-S287
Author(s):  
Evangelina Namburete
Keyword(s):  
Genetic Diversity ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Central Region ◽  
Disease Spread ◽  
Whole Genome ◽  
Drug Resistant ◽  
Illumina Hiseq ◽  
Drug Resistant Tuberculosis ◽  
Resistant Tuberculosis

Abstract Background Knowing the genetic diversity of M. tuberculosis strains causing drug-resistant tuberculosis (DR-TB) in high burden TB and low resources countries such as Mozambique is a key factor to TB disease spread control and world TB epidemic control. Whole-genome sequencing (WGS) better describes molecular diversity, lineages and sub lineages, relationship between strains, underline mutations conferring drug-resistant TB, which may not be shown by molecular and phenotypic tests. As far as we know this is the first study that describes genetic diversity of M. tuberculosis strains causing DR-TB and using WGS in central region of Mozambique.We aim to describe genetic diversity of M. tuberculosis strains causing DR-TB in central Mozambique. Methods A total of 35 strains from Beira Mozambique were evaluated with genotypic tests (Genotype MTBDRplus™, and MTBDRsl™); phenotypic (MGIT-SIRE™) and DST. All isolates resistant to isoniazid (H) or rifampicin (R) or both were submitted to WGS Illumina HiSeq 2000 and analyzed with TB profiler database and phylogenetic tree was done using Figtree tool. This was a descriptive cross-sectional study. Results WGS shown that strains analyzed, belongs to three of six major lineages, with Lineage 4: 25(71.4%); Lineage 1: 5(14.3%); and Lineage 2 Beijing family: 5(14.3%)]. All pre-XDR strains 3(8.6%) were from lineage 4.3. By WGS, all 35 strains had any mutations conferring DR-TB while in one strain, mutation was not shown by genotypic neither phenotypic DST. Compared with genotypic tests, WGS had best performance in showing mutation conferring resistance to etambutol 12/35 (34.3%) and 7/35 (20%). Conclusion The DR-TB disease in Beira Mozambique is mainly caused by M. tuberculosis strains of Lineage 4, sub-lineage 3 although lineage 1 and 2 are also present. WGS shows underline mutations causing DR–TB that are not detected by genotypic and phenotypic DST test. Disclosures All authors: No reported disclosures.

scholarly journals Whole-Genome Sequencing to Characterize Monogenic and Polygenic Contributions in Patients Hospitalized With Early-Onset Myocardial Infarction

Circulation ◽  
2019 ◽  
Vol 139 (13) ◽  
pp. 1593-1602 ◽  
Author(s):  
Amit V. Khera ◽  
Mark Chaffin ◽  
Seyedeh M. Zekavat ◽  
Ryan L. Collins ◽  
Carolina Roselli ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Early Onset ◽  
Whole Genome

scholarly journals Defining the genetic basis of early onset hereditary spastic paraplegia using whole genome sequencing

Neurogenetics ◽  
2016 ◽  
Vol 17 (4) ◽  
pp. 265-270 ◽  
Author(s):  
Kishore R Kumar ◽  
G.M. Wali ◽  
Mahesh Kamate ◽  
Gautam Wali ◽  
André E Minoche ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Hereditary Spastic Paraplegia ◽  
Early Onset ◽  
Genetic Basis ◽  
Whole Genome ◽  
Spastic Paraplegia

scholarly journals Universal Human Papillomavirus Typing Assay: Whole-Genome Sequencing following Target Enrichment

2016 ◽  
Vol 55 (3) ◽  
pp. 811-823 ◽  
Author(s):  
Tengguo Li ◽  
Elizabeth R. Unger ◽  
Dhwani Batra ◽  
Mili Sheth ◽  
Martin Steinau ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Target Enrichment ◽  
Degenerate Primers ◽  
Illumina Hiseq ◽  
Hpv Typing ◽  
Type Assignment ◽  
Hpv Types

ABSTRACTWe designed a universal human papillomavirus (HPV) typing assay based on target enrichment and whole-genome sequencing (eWGS). The RNA bait included 23,941 probes targeting 191 HPV types and 12 probes targeting beta-globin as a control. We used the Agilent SureSelect XT2 protocol for library preparation, Illumina HiSeq 2500 for sequencing, and CLC Genomics Workbench for sequence analysis. Mapping stringency for type assignment was determined based on 8 (6 HPV-positive and 2 HPV-negative) control samples. Using the optimal mapping conditions, types were assigned to 24 blinded samples. eWGS results were 100% concordant with Linear Array (LA) genotyping results for 9 plasmid samples and fully or partially concordant for 9 of the 15 cervical-vaginal samples, with 95.83% overall type-specific concordance for LA genotyping. eWGS identified 7 HPV types not included in the LA genotyping. Since this method does not involve degenerate primers targeting HPV genomic regions, PCR bias in genotype detection is minimized. With further refinements aimed at reducing cost and increasing throughput, this first application of eWGS for universal HPV typing could be a useful method to elucidate HPV epidemiology.

A blaVIM-1 positive Aeromonas hydrophila strain in a near-drowning patient: evidence for interspecies plasmid transfer within the patient

2019 ◽  
Vol 14 (14) ◽  
pp. 1191-1197 ◽  
Author(s):  
Thijs Bosch ◽  
Rogier Schade ◽  
Fabian Landman ◽  
Leo Schouls ◽  
Karin van Dijk
Keyword(s):  
Gene Transfer ◽  
Horizontal Gene Transfer ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Resistance Genes ◽  
Aeromonas Hydrophila ◽  
Whole Genome ◽  
Illumina Hiseq ◽  
Near Drowning ◽  
Long Read

Aim: To show that a strain of Aeromonas hydrophila became resistant to carbapenems by interspecies transfer of a plasmid using long-read sequencing. Material & methods: Whole genome sequencing of the four isolates was done using Illumina Hiseq, while the plasmid was reconstructed using the MinION sequencer. The resistome was identified with ResFinder. Results: Whole genome sequencing and long-read sequencing showed that all isolates carried a blaVIM-1 gene located on a 165 kb incA/C plasmid. ResFinder confirmed that the resistome of the plasmid, comprising 13 resistance genes, was identical within all isolates. Discussion: Long-read sequencing using the MinION successfully reconstructed a plasmid that was identical in all isolates, providing evidence for horizontal gene transfer of this blaVIM-1 gene carrying plasmid within the patient.

scholarly journals Draft genome of tule elk Cervus elaphus nannodes

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1691
Author(s):  
Jessica E. Mizzi ◽  
Zachary T. Lounsberry ◽  
C. Titus Brown ◽  
Benjamin N. Sacks
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cervus Elaphus ◽  
Draft Genome ◽  
Genetic Bottleneck ◽  
Genomic Research ◽  
Whole Genome ◽  
Base Pairs ◽  
Illumina Hiseq ◽  
Tule Elk

This paper presents the first draft genome of the tule elk (Cervus elaphus nannodes), a subspecies native to California that underwent an extreme genetic bottleneck in the late 1800s.  The genome was generated from Illumina HiSeq 3000 whole genome sequencing of four individuals, resulting in the assembly of 2.395 billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp. This genome provides a resource to facilitate future genomic research on elk and other cervids.

scholarly journals Whole genome sequencing facilitates intragenic variant interpretation following modifier screening in C. elegans

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Francesca Jean ◽  
Susan Stasiuk ◽  
Tatiana Maroilley ◽  
Catherine Diao ◽  
Andrew Galbraith ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
High Throughput ◽  
Age Of Onset ◽  
Model Systems ◽  
Temperature Sensitive ◽  
Whole Genome ◽  
Genomic Context ◽  
Traditional Methods ◽  
C Elegans

Abstract Background Intragenic modifiers (in-phase, second-site variants) are known to have dramatic effects on clinical outcomes, affecting disease attributes such as severity or age of onset. However, despite their clinical importance, the focus of many genetic screens in model systems is on the discovery of extragenic variants, with many labs still relying upon more traditional methods to identify modifiers. However, traditional methods such as PCR and Sanger sequencing can be time-intensive and do not permit a thorough understanding of the intragenic modifier effects in the context of non-isogenic genomic backgrounds. Results Here, we apply high throughput approaches to identify and understand intragenic modifiers using Caenorhabditis elegans. Specifically, we applied whole genome sequencing (WGS) to a mutagen-induced forward genetic screen to identify intragenic suppressors of a temperature-sensitive zyg-1(it25) allele in C. elegans. ZYG-1 is a polo kinase that is important for centriole function and cell divisions, and mutations that truncate its human orthologue, PLK4, have been associated with microcephaly. Combining WGS and CRISPR/Cas9, we rapidly identify intragenic modifiers, show that these variants are distributed non-randomly throughout zyg-1 and that genomic context plays an important role on phenotypic outcomes. Conclusions Ultimately, our work shows that WGS facilitates high-throughput identification of intragenic modifiers in clinically relevant genes by reducing hands-on research time and overall costs and by allowing thorough understanding of the intragenic phenotypic effects in the context of different genetic backgrounds.

scholarly journals Chorea-acanthocytosis

2018 ◽  
Vol 4 (3) ◽  
pp. e242 ◽  
Author(s):  
Susan Walker ◽  
Rubina Dad ◽  
Bhooma Thiruvahindrapuram ◽  
Muhammed Ikram Ullah ◽  
Arsalan Ahmad ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Autosomal Recessive ◽  
Rare Variants ◽  
Homozygous Deletion ◽  
Whole Genome ◽  
Illumina Hiseq ◽  
Neurologic Disorders ◽  
The Family ◽  
Multigenerational Family

ObjectiveTo determine a molecular diagnosis for a large multigenerational family of South Asian ancestry with seizures, hyperactivity, and episodes of tongue biting.MethodsTwo affected individuals from the family were analyzed by whole-genome sequencing on the Illumina HiSeq X platform, and rare variants were prioritized for interpretation with respect to the phenotype.ResultsA previously undescribed, 1-kb homozygous deletion was identified in both individuals sequenced, which spanned 2 exons of the VPS13A gene, and was found to segregate in other family members.ConclusionsVPS13A is associated with autosomal recessive chorea-acanthocytosis, a diagnosis consistent with the phenotype observed in this family. Whole-genome sequencing presents a comprehensive and agnostic approach for detecting diagnostic mutations in families with rare neurologic disorders.

scholarly journals Comparative analysis of novel MGISEQ-2000 sequencing platform vs Illumina HiSeq 2500 for whole-genome sequencing

2019 ◽  
Author(s):  
Dmitriy Korostin ◽  
Nikolay Kulemin ◽  
Vladimir Naumov ◽  
Vera Belova ◽  
Dmitriy Kwon ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Variant Calling ◽  
Advanced Technology ◽  
Lower Sensitivity ◽  
Its Sequencing ◽  
Whole Genome ◽  
Illumina Hiseq ◽  
Sequencing Platform ◽  
Wide Range

AbstractBackgroundMGISEQ-2000 developed by MGI Tech Co. Ltd. (a subsidiary of the BGI Group) is a new competitor of such next-generation sequencing platforms as NovaSeq and HiSeq (Illumina). Its sequencing principle is based on the DNB and cPAS technologies, which were also used in the previous version of the BGISEQ-500 device. However, the reagents for MGISEQ-2000 have been refined and the platform utilizes updated software. The cPAS method is an advanced technology based on cPAL previously created by Complete Genomics.ResultIn this paper, the authors compare the results of the whole-genome sequencing of a DNA sample from a Russian female donor performed on MGISEQ-2000 and Illumina HiSeq 2500 (both PE150). Two platforms were compared in terms of sequencing quality, number of errors and performance. Additionally, we performed variant calling using four different software packages: Samtools mpileaup, Strelka2, Sentieon, and GATK. The accuracy of single nucleotide polymorphism (SNP) detection was similar in the data generated by MGISEQ-2000 and HiSeq 2500, which was used as a reference. At the same time, a separate indel analysis of the overall error rate revealed similar FPR values and lower sensitivity.Conclusionsit may be concluded with confidence that the data generated by the analyzed sequencing systems is characterized by comparable magnitudes of error and that MGISEQ-2000 can be used for a wide range of research tasks on par with HiSeq 2500.

scholarly journals Draft genome of tule elk Cervus canadensis nannodes

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 1691
Author(s):  
Jessica E. Mizzi ◽  
Zachary T. Lounsberry ◽  
C. Titus Brown ◽  
Benjamin N. Sacks
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Cervus Elaphus ◽  
Draft Genome ◽  
Genetic Bottleneck ◽  
Genomic Research ◽  
Whole Genome ◽  
Base Pairs ◽  
Illumina Hiseq ◽  
Tule Elk

This paper presents the first draft genome of the tule elk (Cervus elaphus nannodes), a subspecies native to California that underwent an extreme genetic bottleneck in the late 1800s.  The genome was generated from Illumina HiSeq 3000 whole genome sequencing of four individuals, resulting in the assembly of 2.395 billion base pairs (Gbp) over 602,862 contigs over 500 bp and N50 = 6,885 bp. This genome provides a resource to facilitate future genomic research on elk and other cervids.

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