scholarly journals Discovering disease causing variants in dogs through whole genome sequencing

2017 ◽  
Author(s):  
◽  
Ana Leticia Kolicheski
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Neuronal Ceroid Lipofuscinosis ◽  
Splice Site Mutation ◽  
Whole Genome ◽  
Site Mutation ◽  
Sequencing Technologies ◽  
Current State ◽  
Canine Genetics ◽  
Canine Diseases

This dissertation focuses on the use of whole genome sequencing (WGS) for the identification of disease causing variants in canine genomes. A brief review on the historical milestones of genetics, the creation and popularization of the fast throughput DNA sequencing technologies and their advantages and potential problems and biases, the importance of the study of canine genetics and the current state of the canine genome assembly is presented. Our lab sequenced [about]100 dogs in the attempt to discover disease-causing variants. So far 20 such variants have been identified. This dissertation contains detailed accounts of the discovery variants likely to be responsible for four canine diseases. Those diseases are: Paroxysmal dyskinesia in Soft Coated Wheaten Terriers that is associated to the missense mutation PIGN:c.398C greater than T; two different forms of neuronal ceroid lipofuscinosis, one in Australian Cattle dogs caused by CLN5:c.619C greater than T, and one in the Cane Corso caused by the splice site mutation PPT1c.124+1 [greater than] A; and a Shiba Inu GM2 gangliosidosis caused by HEXB.c:948_950delCCT. Furthermore, examples of not so successful attempts, possible reasons for failures and suggestions to successfully conclude other ongoing investigations.

scholarly journals Long-read sequencing across the C9orf72 ‘GGGGCC’ repeat expansion: implications for clinical use and genetic discovery efforts in human disease

2018 ◽  
Author(s):  
Mark T. W. Ebbert ◽  
Stefan Farrugia ◽  
Jonathon Sens ◽  
Karen Jansen-West ◽  
Tania F. Gendron ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Repeat Expansion ◽  
Whole Genome ◽  
Short Read ◽  
Short Read Sequencing ◽  
Sequencing Technologies ◽  
Long Read ◽  
Repeat Expansions ◽  
Targeted Approach

AbstractBackground: Many neurodegenerative diseases are caused by nucleotide repeat expansions, but most expansions, like the C9orf72 ‘GGGGCC’ (G4C2) repeat that causes approximately 5-7% of all amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) cases, are too long to sequence using short-read sequencing technologies. It is unclear whether long-read sequencing technologies can traverse these long, challenging repeat expansions. Here, we demonstrate that two long-read sequencing technologies, Pacific Biosciences’ (PacBio) and Oxford Nanopore Technologies’ (ONT), can sequence through disease-causing repeats cloned into plasmids, including the FTD/ALS-causing G4C2 repeat expansion. We also report the first long-read sequencing data characterizing the C9orf72 G4C2 repeat expansion at the nucleotide level in two symptomatic expansion carriers using PacBio whole-genome sequencing and a no-amplification (No-Amp) targeted approach based on CRISPR/Cas9.Results: Both the PacBio and ONT platforms successfully sequenced through the repeat expansions in plasmids. Throughput on the MinlON was a challenge for whole-genome sequencing; we were unable to attain reads covering the human C9orf72 repeat expansion using 15 flow cells. We obtained 8x coverage across the C9orf72 locus using the PacBio Sequel, accurately reporting the unexpanded allele at eight repeats, and reading through the entire expansion with 1324 repeats (7941 nucleotides). Using the No-Amp targeted approach, we attained >800x coverage and were able to identify the unexpanded allele, closely estimate expansion size, and assess nucleotide content in a single experiment. We estimate the individual’s repeat region was >99% G4C2 content, though we cannot rule out small interruptions.Conclusions: Our findings indicate that long-read sequencing is well suited to characterizing known repeat expansions, and for discovering new disease-causing, disease-modifying, or risk-modifying repeat expansions that have gone undetected with conventional short-read sequencing. The PacBio No-Amp targeted approach may have future potential in clinical and genetic counseling environments. Larger and deeper long-read sequencing studies in C9orf72 expansion carriers will be important to determine heterogeneity and whether the repeats are interrupted by non-G4C2 content, potentially mitigating or modifying disease course or age of onset, as interruptions are known to do in other repeat-expansion disorders. These results have broad implications across all diseases where the genetic etiology remains unclear.

scholarly journals Will whole-genome sequencing become the first-line genetic analysis for male infertility in the near future?

2021 ◽  
Vol 31 (1) ◽  
Author(s):  
Farah Ghieh ◽  
Anne-Laure Barbotin ◽  
Clara Leroy ◽  
François Marcelli ◽  
Nelly Swierkowsky-Blanchard ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
Male Infertility ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Objective Evaluation ◽  
Screening Strategy ◽  
Candidate Gene Approach ◽  
Whole Genome ◽  
Sequencing Technologies ◽  
Whole Exome

AbstractWhereas the initially strategy for the genetic analysis of male infertility was based on a candidate gene approach, the development of next-generation sequencing technologies (such as whole-exome sequencing (WES)) provides an opportunity to analyze many genes in a single procedure. In order to recommend WES or whole-genome sequencing (WGS) after genetic counselling, an objective evaluation of the current genetic screening strategy for male infertility is required, even if, at present, we have to take into consideration the complexity of such a procedure, not discussed in this commentary.

scholarly journals Genomic Diversity of the Ostreid Herpesvirus Type 1 Across Time and Location and Among Host Species

2021 ◽  
Vol 12 ◽  
Author(s):  
Benjamin Morga ◽  
Maude Jacquot ◽  
Camille Pelletier ◽  
Germain Chevignon ◽  
Lionel Dégremont ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Phylogenetic Analyses ◽  
Genomic Diversity ◽  
Microbial Pathogens ◽  
Whole Genome ◽  
Site Mutation ◽  
Herpesvirus Type ◽  
New Variant ◽  
Genomic Regions

The mechanisms underlying virus emergence are rarely well understood, making the appearance of outbreaks largely unpredictable. This is particularly true for pathogens with low per-site mutation rates, such as DNA viruses, that do not exhibit a large amount of evolutionary change among genetic sequences sampled at different time points. However, whole-genome sequencing can reveal the accumulation of novel genetic variation between samples, promising to render most, if not all, microbial pathogens measurably evolving and suitable for analytical techniques derived from population genetic theory. Here, we aim to assess the measurability of evolution on epidemiological time scales of the Ostreid herpesvirus 1 (OsHV-1), a double stranded DNA virus of which a new variant, OsHV-1 μVar, emerged in France in 2008, spreading across Europe and causing dramatic economic and ecological damage. We performed phylogenetic analyses of heterochronous (n = 21) OsHV-1 genomes sampled worldwide. Results show sufficient temporal signal in the viral sequences to proceed with phylogenetic molecular clock analyses and they indicate that the genetic diversity seen in these OsHV-1 isolates has arisen within the past three decades. OsHV-1 samples from France and New Zealand did not cluster together suggesting a spatial structuration of the viral populations. The genome-wide study of simple and complex polymorphisms shows that specific genomic regions are deleted in several isolates or accumulate a high number of substitutions. These contrasting and non-random patterns of polymorphism suggest that some genomic regions are affected by strong selective pressures. Interestingly, we also found variant genotypes within all infected individuals. Altogether, these results provide baseline evidence that whole genome sequencing could be used to study population dynamic processes of OsHV-1, and more broadly herpesviruses.

scholarly journals Research advances in and prospects of ornamental plant genomics

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Tangchun Zheng ◽  
Ping Li ◽  
Lulu Li ◽  
Qixiang Zhang
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Ornamental Plants ◽  
Ornamental Plant ◽  
Sequence Information ◽  
Whole Genome ◽  
Plant Genomics ◽  
Plant Resources ◽  
Sequencing Technologies ◽  
Long Time

AbstractThe term ‘ornamental plant’ refers to all plants with ornamental value, which generally have beautiful flowers or special plant architectures. China is rich in ornamental plant resources and known as the “mother of gardens”. Genomics is the science of studying genomes and is useful for carrying out research on genome evolution, genomic variations, gene regulation, and important biological mechanisms based on detailed genome sequence information. Due to the diversity of ornamental plants and high sequencing costs, the progress of genome research on ornamental plants has been slow for a long time. With the emergence of new sequencing technologies and a reduction in costs since the whole-genome sequencing of the first ornamental plant (Prunus mume) was completed in 2012, whole-genome sequencing of more than 69 ornamental plants has been completed in <10 years. In this review, whole-genome sequencing and resequencing of ornamental plants will be discussed. We provide analysis with regard to basic data from whole-genome studies of important ornamental plants, the regulation of important ornamental traits, and application prospects.

scholarly journals Whole-Genome Sequencing of Bacterial Pathogens: the Future of Nosocomial Outbreak Analysis

2017 ◽  
Vol 30 (4) ◽  
pp. 1015-1063 ◽  
Author(s):  
Scott Quainoo ◽  
Jordy P. M. Coolen ◽  
Sacha A. F. T. van Hijum ◽  
Martijn A. Huynen ◽  
Willem J. G. Melchers ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Health Care Professionals ◽  
Resistant Bacteria ◽  
Whole Genome ◽  
Nosocomial Outbreak ◽  
Icu Patients ◽  
Outbreak Management ◽  
Sequencing Technologies ◽  
Analysis Tools

SUMMARY Outbreaks of multidrug-resistant bacteria present a frequent threat to vulnerable patient populations in hospitals around the world. Intensive care unit (ICU) patients are particularly susceptible to nosocomial infections due to indwelling devices such as intravascular catheters, drains, and intratracheal tubes for mechanical ventilation. The increased vulnerability of infected ICU patients demonstrates the importance of effective outbreak management protocols to be in place. Understanding the transmission of pathogens via genotyping methods is an important tool for outbreak management. Recently, whole-genome sequencing (WGS) of pathogens has become more accessible and affordable as a tool for genotyping. Analysis of the entire pathogen genome via WGS could provide unprecedented resolution in discriminating even highly related lineages of bacteria and revolutionize outbreak analysis in hospitals. Nevertheless, clinicians have long been hesitant to implement WGS in outbreak analyses due to the expensive and cumbersome nature of early sequencing platforms. Recent improvements in sequencing technologies and analysis tools have rapidly increased the output and analysis speed as well as reduced the overall costs of WGS. In this review, we assess the feasibility of WGS technologies and bioinformatics analysis tools for nosocomial outbreak analyses and provide a comparison to conventional outbreak analysis workflows. Moreover, we review advantages and limitations of sequencing technologies and analysis tools and present a real-world example of the implementation of WGS for antimicrobial resistance analysis. We aimed to provide health care professionals with a guide to WGS outbreak analysis that highlights its benefits for hospitals and assists in the transition from conventional to WGS-based outbreak analysis.

scholarly journals Comparison of Molecular and In Silico Salmonella Serotyping for Salmonella Surveillance

2021 ◽  
Vol 9 (5) ◽  
pp. 955
Author(s):  
Linda Chui ◽  
Christina Ferrato ◽  
Vincent Li ◽  
Sara Christianson
Keyword(s):  
Public Health ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Dna Microarray ◽  
In Silico ◽  
Whole Genome ◽  
Sequencing Technology ◽  
Outbreak Management ◽  
Sequencing Technologies ◽  
Processing Cost

Salmonella surveillance and outbreak management is a key function of public health. Laboratories are shifting from antigenic serotype determination to molecular methods including microarray or whole genome sequencing technologies. The objective of this study was to compare the Check&Trace Salmonella™ DNA microarray (CTS), a commercially available assay with the Salmonella in silico typing resource (SISTR), which uses whole genome sequencing technology for serotyping clinical Salmonella strains in Alberta, Canada, collected over an 18-month period. A high proportion of isolates (96.3%) were successfully typed by both systems. SISTR is a powerful tool for laboratories which already have a WGS infrastructure in place, whereas smaller laboratories can benefit from a commercial microarray system and reduce the processing cost per isolate compared to traditional serotyping.

scholarly journals Coverage Bias and Sensitivity of Variant Calling for Four Whole-genome Sequencing Technologies

PLoS ONE ◽  
2013 ◽  
Vol 8 (6) ◽  
pp. e66621 ◽  
Author(s):  
Nora Rieber ◽  
Marc Zapatka ◽  
Bärbel Lasitschka ◽  
David Jones ◽  
Paul Northcott ◽  
...  
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Variant Calling ◽  
Whole Genome ◽  
Sequencing Technologies ◽  
Coverage Bias

Currents in Contemporary Bioethics

2012 ◽  
Vol 40 (3) ◽  
pp. 682-689 ◽  
Author(s):  
Mark A. Rothstein
Keyword(s):  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Family Health ◽  
Clinical Applications ◽  
Genome Project ◽  
Whole Genome ◽  
Health History ◽  
Sequencing Technologies ◽  
Substantial Risk ◽  
The Human Genome Project

From the earliest days of the Human Genome Project, the holy grail of genomics was the ability to perform whole-genome sequencing quickly, accurately, and relatively inexpensively so that the benefits of genomics would be widely available in clinical settings. Although the mythical $1,000 genome sequence seemed elusive for many years, next-generation sequencing technologies and other recent advances clearly indicate that inexpensive whole-genome sequencing is at hand.Whole-genome sequencing has demonstrable value in elucidating the genetic etiology of rare disorders, in identifying atypical variants in common diseases, in determining pharmacogenomically appropriate drugs and dosages, in performing tumor genome sequencing, and in aiding other clinical applications for the diagnosis and treatment of individuals who are symptomatic or whose family health history places them at substantial risk. Undoubtedly, the clinical applications of wholegenome sequencing will increase in the future.

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