scholarly journals Gene patent practice across plant and human genomes

2015 ◽  
Vol 33 (10) ◽  
pp. 1033-1038 ◽  
Author(s):  
Osmat A Jefferson ◽  
Deniz Köllhofer ◽  
Thomas H Ehrich ◽  
Richard A Jefferson
Keyword(s):  
Gene Patent ◽  
Human Genomes

scholarly journals A study of transposable element-associated structural variations (TASVs) using a de novo-assembled Korean genome

2021 ◽  
Author(s):  
Seyoung Mun ◽  
Songmi Kim ◽  
Wooseok Lee ◽  
Keunsoo Kang ◽  
Thomas J. Meyer ◽  
...  
Keyword(s):  
Genome Sequencing ◽  
Genome Assembly ◽  
De Novo ◽  
Personal Genome ◽  
Human Populations ◽  
Whole Genome ◽  
Structural Variations ◽  
Insert Size ◽  
Human Genomes ◽  
Next Generation Sequencing Ngs

AbstractAdvances in next-generation sequencing (NGS) technology have made personal genome sequencing possible, and indeed, many individual human genomes have now been sequenced. Comparisons of these individual genomes have revealed substantial genomic differences between human populations as well as between individuals from closely related ethnic groups. Transposable elements (TEs) are known to be one of the major sources of these variations and act through various mechanisms, including de novo insertion, insertion-mediated deletion, and TE–TE recombination-mediated deletion. In this study, we carried out de novo whole-genome sequencing of one Korean individual (KPGP9) via multiple insert-size libraries. The de novo whole-genome assembly resulted in 31,305 scaffolds with a scaffold N50 size of 13.23 Mb. Furthermore, through computational data analysis and experimental verification, we revealed that 182 TE-associated structural variation (TASV) insertions and 89 TASV deletions contributed 64,232 bp in sequence gain and 82,772 bp in sequence loss, respectively, in the KPGP9 genome relative to the hg19 reference genome. We also verified structural differences associated with TASVs by comparative analysis with TASVs in recent genomes (AK1 and TCGA genomes) and reported their details. Here, we constructed a new Korean de novo whole-genome assembly and provide the first study, to our knowledge, focused on the identification of TASVs in an individual Korean genome. Our findings again highlight the role of TEs as a major driver of structural variations in human individual genomes.

scholarly journals NGS-based identification and tracing of microsatellite instability from minute amounts DNA using inter-Alu-PCR

2020 ◽  
Author(s):  
Fangyan Yu ◽  
Ka Wai Leong ◽  
Alexander Makrigiorgos ◽  
Viktor A Adalsteinsson ◽  
Ioannis Ladas ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Analysis Tool ◽  
Circulating Dna ◽  
Liquid Biopsies ◽  
Software Analysis ◽  
Multiplexed Pcr ◽  
Human Genomes ◽  
Custom Made ◽  
Alu Element ◽  
Next Generation Sequencing Ngs

Abstract Sensitive detection of microsatellite instability (MSI) in tissue or liquid biopsies using next generation sequencing (NGS) has growing prognostic and predictive applications in cancer. However, the complexities of NGS make it cumbersome as compared to established multiplex-PCR detection of MSI. We present a new approach to detect MSI using inter-Alu-PCR followed by targeted NGS, that combines the practical advantages of multiplexed-PCR with the breadth of information provided by NGS. Inter-Alu-PCR employs poly-adenine repeats of variable length present in every Alu element and provides a massively-parallel, rapid approach to capture poly-A-rich genomic fractions within short 80–150bp amplicons generated from adjacent Alu-sequences. A custom-made software analysis tool, MSI-tracer, enables Alu-associated MSI detection from tissue biopsies or MSI-tracing at low-levels in circulating-DNA. MSI-associated indels at somatic-indel frequencies of 0.05–1.5% can be detected depending on the availability of matching normal tissue and the extent of instability. Due to the high Alu copy-number in human genomes, a single inter-Alu-PCR retrieves enough information for identification of MSI-associated-indels from ∼100 pg circulating-DNA, reducing current limits by ∼2-orders of magnitude and equivalent to circulating-DNA obtained from finger-sticks. The combined practical and informational advantages of inter-Alu-PCR make it a powerful tool for identifying tissue-MSI-status or tracing MSI-associated-indels in liquid biopsies.

Determination of the Number of Conserved Chromosomal Segments Between Species

Genetics ◽  
2001 ◽  
Vol 157 (3) ◽  
pp. 1387-1395 ◽  
Author(s):  
Sudhir Kumar ◽  
Sudhindra R Gadagkar ◽  
Alan Filipski ◽  
Xun Gu
Keyword(s):  
Statistical Approach ◽  
Common Ancestor ◽  
Chromosomal Rearrangements ◽  
Structural Similarity ◽  
The Other ◽  
Segment Length ◽  
Human Genomes ◽  
Genomic Divergence ◽  
Human And Mouse

AbstractGenomic divergence between species can be quantified in terms of the number of chromosomal rearrangements that have occurred in the respective genomes following their divergence from a common ancestor. These rearrangements disrupt the structural similarity between genomes, with each rearrangement producing additional, albeit shorter, conserved segments. Here we propose a simple statistical approach on the basis of the distribution of the number of markers in contiguous sets of autosomal markers (CSAMs) to estimate the number of conserved segments. CSAM identification requires information on the relative locations of orthologous markers in one genome and only the chromosome number on which each marker resides in the other genome. We propose a simple mathematical model that can account for the effect of the nonuniformity of the breakpoints and markers on the observed distribution of the number of markers in different conserved segments. Computer simulations show that the number of CSAMs increases linearly with the number of chromosomal rearrangements under a variety of conditions. Using the CSAM approach, the estimate of the number of conserved segments between human and mouse genomes is 529 ± 84, with a mean conserved segment length of 2.8 cM. This length is <40% of that currently accepted for human and mouse genomes. This means that the mouse and human genomes have diverged at a rate of ∼1.15 rearrangements per million years. By contrast, mouse and rat are diverging at a rate of only ∼0.74 rearrangements per million years.

scholarly journals MODL-21. INTEGRATIVE APPROACHES IN FUNCTIONAL GENOMICS TO IDENTIFY GENETIC DEPENDENCIES IN PEDIATRIC BRAIN CANCER

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii415-iii415
Author(s):  
Claire Sun ◽  
Caroline Drinkwater ◽  
Dhanya Sooraj ◽  
Gabrielle Bradshaw ◽  
Claire Shi ◽  
...  
Keyword(s):  
Functional Genomics ◽  
Precision Medicine ◽  
Brain Cancer ◽  
Human Genomes ◽  
Pediatric Cancer Patients ◽  
Crispr Screen ◽  
The Central Nervous System ◽  
Molecular Aberrations ◽  
Genetic Profiles ◽  
Pediatric Brain

Abstract The precise decoding of human genomes facilitated by the advancements in next-generation sequencing has led to a better understanding of genetic underpinnings of pediatric brain cancers. Indeed, it is now evident that tumours of the same type harbour distinct driving mutations and molecular aberrations that can result in different prognosis and treatment outcomes. The profounder insight into the the identity, amount and types of molecular aberrations has paved the way for the advent of targeted therapies in precision medicine. Nevertheless, less than 10% of pediatric cancer patients harbour actionable mutations. Strictly limited therapeutic options that are firstly available for brain cancers and secondly acceptable for children’s development further impede the breakthrough in the survival rate in pediatric brain cancers. This underscores a desperate need to delve beyond genomic sequencing to identify biomarker coupled therapies that not only featured with treatment efficacy in the central nervous system but also acceptable side effects for children. The Hudson-Monash Paediatric Precision Medicine (HMPPM) Program focuses on utilising genetic profiles of patients’ tumour models to identify new therapeutic targets and repurpose existing ones using high-throughput functional genomics screens (2220 drugs and CRISPR screen of 300 oncogenic genes). Using a large compendium of over sixty patient derived paediatric brain cancer models, we provide proof-of-concept data that shows an integrative pipeline for functional genomics with multi-omics datasets to perform genotype-phenotype correlations and, therefore, identify genetic dependencies. Herein, using several examples in ATRT, DIPG and HGG, we show how functional interrogations can better define molecular subclassification of tumours and identify unique vulnerabilities.

Moving the gene patent debate forward

10.1038/82460 ◽  
2000 ◽  
Vol 18 (12) ◽  
pp. 1319-1320 ◽  
Author(s):  
E. Richard Gold
Keyword(s):  
Gene Patent

scholarly journals A curated dataset of modern and ancient high-coverage shotgun human genomes

2021 ◽  
Vol 8 (1) ◽  
Author(s):  
Pierpaolo Maisano Delser ◽  
Eppie R. Jones ◽  
Anahit Hovhannisyan ◽  
Lara Cassidy ◽  
Ron Pinhasi ◽  
...  
Keyword(s):  
Sequence Data ◽  
Whole Genome ◽  
Reference Dataset ◽  
High Coverage ◽  
Sample Distribution ◽  
Human Samples ◽  
Human Genomes ◽  
Genome Wide ◽  
Genome Wide Data ◽  
Computationally Intensive

AbstractOver the last few years, genome-wide data for a large number of ancient human samples have been collected. Whilst datasets of captured SNPs have been collated, high coverage shotgun genomes (which are relatively few but allow certain types of analyses not possible with ascertained captured SNPs) have to be reprocessed by individual groups from raw reads. This task is computationally intensive. Here, we release a dataset including 35 whole-genome sequenced samples, previously published and distributed worldwide, together with the genetic pipeline used to process them. The dataset contains 72,041,355 sites called across 19 ancient and 16 modern individuals and includes sequence data from four previously published ancient samples which we sequenced to higher coverage (10–18x). Such a resource will allow researchers to analyse their new samples with the same genetic pipeline and directly compare them to the reference dataset without re-processing published samples. Moreover, this dataset can be easily expanded to increase the sample distribution both across time and space.

Long read sequencing reveals sequential complex rearrangements driven by Hepatitis B virus integration

2021 ◽  
Author(s):  
Songbo Wang ◽  
Jiadong Lin ◽  
Xiaofei Yang ◽  
Zihang Li ◽  
Tun Xu ◽  
...  
Keyword(s):  
Hepatitis B ◽  
Clinical Samples ◽  
Metabolic Dysfunction ◽  
Cellular Functions ◽  
Human Genomes ◽  
Long Reads ◽  
B Virus ◽  
Long Read ◽  
Genetic Structures ◽  
Virus Integration

Integration of Hepatitis B (HBV) virus into human genome disrupts genetic structures and cellular functions. Here, we conducted multiplatform long read sequencing on two cell lines and five clinical samples of HBV-induced hepatocellular carcinomas (HCC). We resolved two types of complex viral integration induced genome rearrangements and established a Time-phased Integration and Rearrangement Model (TIRM) to depict their formation progress by differentiating inserted HBV copies with HiFi long reads. We showed that the two complex types were initialized from focal replacements and the fragile virus-human junctions triggered subsequent rearrangements. We further revealed that these rearrangements promoted a prevalent loss-of-heterozygosity at chr4q, accounting for 19.5% of HCC samples in ICGC cohort and contributing to immune and metabolic dysfunction. Overall, our long read based analysis reveals a novel sequential rearrangement progress driven by HBV integration, hinting the structural and functional implications on human genomes.

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