Germline genomic structural variation. Medical search. Frequent questions

His lab is both experimental and computational and is focused on understanding heritable genomic structural variants (SVs) in cancer. (blogspot.com)
Some structural variants are difficult to analyse, e.g. balanced polymorphic inversions with no copy number change. (blogspot.com)
Most large genomes contain thousands of large structural variants (SVs), repetitive regions composed of identical or similar stretches of sequences, mobile elements such as transposons, large insertions, deletions, translocations, and inversions up to millions of bases, with even partial or entire chromosomes altered. (mdanderson.org)
Structural Variants (SVs) caused by the reorganization of the DNA may connect two distal fragments together leading to gene fusions and chimeric proteins when two distant genes are joined into one. (mdanderson.org)
Detects all types of Structural Variants (SVs) down to 5% Variant Allele Fraction for mosaic samples or heterogeneous cancer samples. (mdanderson.org)
BARD1 germline variants induce haploinsufficiency and DNA repair defects in neuroblastoma. (cancer.gov)
Structural variants (SVs) play a crucial role in gene regulation, trait association, and disease in humans. (biomedcentral.com)
PG2 integrates genome and transcriptome sequencing to incorporate protein variants containing amino acid substitutions, insertions, and deletions, as well as non-canonical reading frames, exons, and other variants caused by genomic and transcriptomic variation. (biorxiv.org)
However, recent studies in many organisms and in humans have revealed significant protein sequence variation due to the presence of somatically acquired genetic variants, alternative transcription, and mRNA splicing, which are not necessarily annotated in reference databases. (biorxiv.org)
GRAF™ Pan Genome Reference - contains both small variants (SNPs and INDELs up to several dozens of base-pairs in length) as well as larger structural variants, which are typically difficult to identify from short-read sequencing data. (sevenbridges.com)
This graph is augmented with population-specific structural variants obtained from PacBio HiFi reads. (sevenbridges.com)
GRAF™ Variant Caller - enables integrated calling of SNPs and INDELs, as well as structural variants present in the Genome Graph. (sevenbridges.com)
Available algorithms use one or more sources of evidence, such as read depth, paired-end reads or split reads to predict structural variants. (edu.au)
RESULTS: In this article, we present Socrates (SOft Clip re-alignment To idEntify Structural variants), a highly efficient and effective method for detecting genomic rearrangements in tumours that uses only split-read data. (edu.au)
The method is motivated by the observation that homozygous germline population variants rarely change in the disease and are not affected by loss of heterozygosity. (edu.au)
calls structural variants (SVs) and indels from mapped paired-end sequencing reads. (biogrids.org)
2016. Manta: rapid detection of structural variants and indels for germline and cancer sequencing applications. (biogrids.org)
Detecting variations larger than 50 nucleotide bases called Structural Variants (SV) with current DNA sequencing technology remains challenging in normal tissues, but becomes more problematic with the increased heterogeneity and allele complexity found in tumor tissues. (uconn.edu)
New technologies and analysis methods are enabling genomic structural variants (SVs) to be detected with ever-increasing accuracy, resolution and comprehensiveness. (nabsys.com)
The importance of structural variation in human disease and the difficulty of detecting structural variants larger than 50 base pairs has led to the development of several long-read sequencing technologies and optical mapping platforms. (nabsys.com)
We demonstrate that whole genome maps, constructed from electronic detection of tagged DNA, hundreds of kilobases in length, can be used effectively to facilitate calling of structural variants ranging in size from 300 base pairs to hundreds of kilobase pairs. (nabsys.com)
Evaluation of malignant hyperthermia features in patients with pathogenic or likely pathogenic RYR1 variants disclosedthrough a population genomic screening program. (cdc.gov)
High-resolution structural variants catalogue in a large-scale whole genome sequenced bovine family cohort data. (uliege.be)
For the Kids First study, Genomic Analysis of Esophageal Atresia and Tracheoesophageal Fistulas and Associated Congenital Anomalies , led by Dr. Wendy Chung of Columbia University Health Sciences, 7.45TB of Single Nucleotide Variants and Sequencing Reads were added to the portal in August of this year. (kidsfirstdrc.org)
Heterozygous chromosomal structural variants are widely present in many different organisms. (harvard.edu)
Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. (gla.ac.uk)
Using CRISPR gene editing to model patient-derived MSH6 germline variants in human embryonic stem cells (hESCs). (uconn.edu)
Two variants were found that have been previously identified as pathogenic factors in familial hypercholesteremia and structural disorders of the heart. (biomedcentral.com)
These were subsequently compared with known human variation databases to identify the presence of functionally relevant mutations (for example pathogenic variants). (biomedcentral.com)
Finally, we looked at the genomic locations of the exonic variants to list all the genes that contained these changes. (biomedcentral.com)
Genomic DNA was isolated and amplified using nature for these variants. (cdc.gov)
Two synonymous germline in a majority of these patients.10 13 The same sequence variants were identified in two separate investigators also found somatic sequence variants patients. (cdc.gov)

Somatic mutations of TP53 are among the most common in cancer and germline mutations of TP53 (usually missense) can cause Li-Fraumeni syndrome (LFS). (oncotarget.com)
Germline Elongator mutations in Sonic Hedgehog medulloblastoma. (epfl.ch)
Here we sequence spontaneously arising Eμ-Myc lymphomas to define transgene architecture, somatic mutations, and structural alterations. (edu.au)
The rows contain clinical information, data on EBV-infected cells, and the somatic and germline mutations found. (yusukeokuno.com)
ALL is the most frequent childhood neoplasm characterized by the most various somatic and germline mutations among cancers. (yusukeokuno.com)
CD Genomics utilizes targeted NGS sequencing technology to provide more efficient and accurate targeting of specific genes or mutations, and even to detect low frequency variations in cancer-associated genes. (cd-genomics.com)
Point mutations, indels, copy number variations (CNVs) and rearrangements can be detected. (cd-genomics.com)
Mainly detects germline mutations. (cd-genomics.com)
This panel detects point mutations, insertion-deletions, copy number variations, and fusions (structural variations) in specific genes within the tumor signaling pathway. (cd-genomics.com)
Herein we selected a Mendelian genetics form of familial cancer such as hereditary tumor syndromic endocrine neoplasias caused by highly penetrant germline mutations leading to pheochromocytoma-paraganglioma syndromes. (intechopen.com)
Multiple endocrine neoplasia syndrome type 1 (MEN-1), loss-of-function germline mutations in the tumor suppressor gene MEN1 increase the risk of developing pituitary, parathyroid and pancreatic islet tumors, and less commonly thymic carcinoids, lipomas and benign adrenocortical tumors. (intechopen.com)
In the case of multiple endocrine neoplasia type 2 (MEN 2), gain-of-function germline mutations clustered in specific codons of the RET proto-oncogene increase the risk of developing medullary thyroid carcinoma (MTC), phaeochromocytoma and parathyroid tumors. (intechopen.com)

Integrating pharmacogenomic testing into paired germline and somatic genomic testing in patients with cancer. (cdc.gov)

Some SVs, such as deletions and duplications, change the dosage of DNA and are considered copy number variations (CNVs). (mdanderson.org)
Structural variations (SVs) are changes in chromosomal architecture such as deletions, duplications, translocations, and inversions. (cancer.gov)
This has led to the development of graph-based references, able to naturally represent all polymorphisms, including insertions, deletions, and structural variation. (sevenbridges.com)
We detected copy number variation, frequent insertions and deletions within the sequences of DYZ1 arrays amongst all the three sets of twins used in the present study. (biomedcentral.com)
To help translate these methods to routine research and clinical practice, we developed a sequence-resolved benchmark set for identification of both false-negative and false-positive germline large insertions and deletions. (nabsys.com)
The blue histograms indicate the frequency of the deletions in each genomic region. (yusukeokuno.com)
In striking contrast, complete deletions of band 11p13 result in the Wilms tumor, aniridia, genitourinary malformations, and mental retardation (WAGR) syndrome , which is characterized by structural urinary tract abnormalities without nephropathy. (medscape.com)

An extremely complex form of SVs called chromothripsis, in which dozens to hundreds of breakpoints on one or more chromosomes are involved, was originally reported in different types of cancers as well as in germlines genomes causing developmental and neuronal disorders. (mdanderson.org)
Now in its fourth year, the NIH Common Fund-supported Gabriella Miller Kids First Data Resource Center (Kids First DRC), is a leading resource and platform for the advancement of our fundamental understanding of pediatric cancers and structural birth defects. (kidsfirstdrc.org)
The most common non-clear cell renal cancers have also undergone genomic profiling and are characterised by distinct genomic landscapes. (springer.com)

The discovered PSS motifs and high-throughput forward chemical genomic screening approach should prove useful for the elucidation of endogenous genome remodeling activities of PGBD5 and other domesticated human DNA transposases and recombinases. (biomedcentral.com)
Evolutionary genetics is at an exciting crossroads due to the growing ability to functionally characterize non-coding regions enabled by high-throughput genomic technologies. (harvard.edu)
Nakken S, Saveliev V, Hofmann O, Møller P, Myklebost O , Hovig E (2020) Cancer Predisposition Sequencing Reporter (CPSR): a flexible variant report engine for high-throughput germline screening in cancer. (uib.no)

The motivation for the proposed work is the need for an integrated understanding of inherited genetic variation and acquired mutational events in the host and tumor to enable improved risk assessment and develop rational, evidence-based therapies to improve patient outcomes. (cancer.gov)
2) Discover and prioritize somatic SVs using whole genome-sequencing (WGS) of 146 diagnostic NB pairs (tumor, germline), and 60 relapsed NB trios (diagnostic, relapsed and germline). (cancer.gov)
Manta is optimized for analysis of germline variation in small sets of individuals and somatic variation in tumor/normal sample pairs. (biogrids.org)
The method is designed for rapid analysis on standard compute hardware: NA12878 at 50x genomic coverage is analyzed in less than 20 minutes on a 20 core server, and most WGS tumor/normal analyses can be completed within 2 hours. (biogrids.org)

Moreover, we conducted whole-exome sequencing of germline DNA and chondrosarcoma tissue to further explore the pathogenesis of MS. (biomedcentral.com)

Optical Genome Mapping is non-sequencing technology capable of analyzing large eukaryotic genomes and their structural features at a high resolution by evaluation of patterns generated by fluorophore tags labeled to specific sequence motifs within extremely long DNA molecules, of more than 300 kb (3, 4). (mdanderson.org)
We show that this approach works well on deletion, duplication and inversion call types in germline data by constructing a fully automated SV calling engine (SVE) that runs eight popular calling algorithms and utilizes the freely available 1000 Genomes Phase 3 high coverage data set. (uconn.edu)
Detection and effects of structural variation and polymorphic transposable element insertions in diverse mouse genomes. (uconn.edu)
Illumina Basespace Sequence hub, Dragon Germline 3.4.5 (DRAGEN Host Software Version 05.021.332.3.4.5 and Bio-IT Processor Version 0x04261818) was used for mapping the sequenced genomes with the human reference genome (GRCh38.p2) and the subsequent variant calling. (biomedcentral.com)

Recently, recurrent genomic rearrangements in intron 1 of TP53 have been described in osteosarcoma (OS), a highly malignant neoplasm of bone belonging to the spectrum of LFS tumors. (oncotarget.com)
Genomic rearrangements in Arabidopsis considered as quantitative traits. (nature.com)
These studies implicate a potential mechanism suppressing the loss of genetic material after chromosome pulverization, although how distinct patterns of rearrangements arise in cancer and germline disorders remains unclear. (nature.com)
We also identify multiple cases of catastrophic chromosomal rearrangements known as chromoanagenesis, including somatic chromoanasynthesis, and extreme balanced germline chromothripsis events involving up to 65 breakpoints and 60.6 Mb across four chromosomes, further defining rare categories of extreme cxSV. (biomedcentral.com)
Despite these discoveries, the patterns, rates, and properties of cxSVs have primarily been the focus of cancer genomics and such rearrangements remain largely underappreciated in the human germline. (biomedcentral.com)
Frequently, multiple technologies and ad hoc methods are required to obtain a consensus regarding the location, size and nature of a structural variant, with no approach able to reliably bridge the gap of variant sizes between the domain of short-read approaches and the largest rearrangements observed with optical mapping. (nabsys.com)

We will test our hypothesis in three specific aims: 1) Identify rare germline SVs associated with NB through a SV-based association study of 7,500 NB cases and 15,000 healthy children as controls and evaluation of heritability in 642 patient-parent trios. (cancer.gov)

Recurrent and/or clonally enriched SVs will be prioritized using an integrative transcriptomic and (epi)genomic approach and validated in two independent cohorts comprised of 1,158 NBs. (cancer.gov)
We benchmarked PG2 using synthetic data and genomic, transcriptomic, and proteomic analysis of human leukemia cells. (biorxiv.org)

And structural variation hotspots in the human genome are formed by single processes at each hotspot, that is the underlying sequence drives the kind of SV seen in a hotspot. (blogspot.com)
Megabase size molecules of genomic DNA are isolated and labelled at a specific 6 or 7 base pair sequence motifs. (mdanderson.org)
In the present study we used DYZ1, a satellite fraction present in the form of tandem arrays on the long arm of the human Y chromosome, as a tool to uncover sequence variations between the monozygotic males. (biomedcentral.com)
DYZ1 showed both sequence and copy number variation between the MZT males. (biomedcentral.com)
Sequence variation was also noticed between germline and blood DNA samples of the same individual as we observed at least in one set of sample. (biomedcentral.com)
An allele is one of two or more versions of DNA sequence (a single base or a segment of bases) at a given genomic location. (genome.gov)
The sensitivity of CGH in detecting fine changes in CNV depends on the representation of the genomic sequence of the clones, probe characteristics and signal-to-noise ratios. (bio-rad.com)
Results: One non-synonymous germline sequence variant iants as well as multiple haplotypes were observed was identified in one patient. (cdc.gov)

GRAF™ Germline Variant Detection Workflow - uses a Pan-Genome graph containing genetic information from many populations around the world. (sevenbridges.com)
GRAF™ Extended Germline Variant Detection Workflow - makes use of an ancestry-aware genome graph (i.e. a population-specific reference) in order to increase sensitivity towards the population represented by the graph reference. (sevenbridges.com)
Consequently, graph references provide the means to both accurately detect structural variation and thus reduce spurious variant calls. (sevenbridges.com)
We demonstrate using simulated and real data that Socrates performs well compared with a number of existing structural variant detection tools. (edu.au)
To enable functional analysis of human transposase-derived genes, we combined forward chemical genetic hypoxanthine-guanine phosphoribosyltransferase 1 ( HPRT1 ) screening with massively parallel paired-end DNA sequencing and structural variant genome assembly and analysis. (biomedcentral.com)

Schatz, Michael 2018-04-30 00:00:00 Structural variations are the greatest source of genetic variation, but they remain poorly understood because of technological limitations. (deepdyve.com)
Our long-term goal is to improve the outcome of children with NB by defining the inherited and acquired genetic/genomic basis of the disease and response to therapy. (cancer.gov)
Structural genomic variations (SVs) are generally regarded as genetic changes with a size larger than 50 bp [ 1 ]. (biomedcentral.com)
Recent advances in nucleic acid sequencing now permit rapid and genome-scale analysis of genetic variation and transcription, enabling population-scale studies of human biology, disease, and diverse organisms. (biorxiv.org)
These genetic changes can occur by multiple mechanisms that can be inherited (found in the germline) or acquired (somatic). (medscape.com)
In addition, transposons are a major source of structural genetic variation in human populations [ 2 ]. (biomedcentral.com)
Here, we sought to develop a forward genetic screening approach suitable for the elucidation of endogenous genomic substrates of human DNA transposases and recombinases. (biomedcentral.com)
Abstract: Effective interpretation of genome function and genetic variation requires a shift from epigenetic mapping of cis-regulatory elements (CREs) to characterization of endogenous function. (harvard.edu)
Access to human germline cell types for study is limited, and little is known about the underlying genetic regulation of human gametogenesis. (harvard.edu)
Both processes require genetic variation in adaptive traits within populations. (harvard.edu)
Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1,2,3. (gla.ac.uk)

Here, we report the HPRT1 mutational spectrum induced by the human transposase PGBD5, including PGBD5-specific signal sequences (PSS) that serve as potential genomic rearrangement substrates. (biomedcentral.com)

Furthermore, there is significant purifying selection against large and gene-disruptive copy number variations (CNVs), indicating their considerable phenotypic impact. (biomedcentral.com)
However, large CNVs and SVs have a high chance of affecting important genomic elements, which could lead to congenital disease. (biomedcentral.com)
It has been reported that the aberrant DNA methylation may result in copy number variations (CNVs), and the CNVs may alter the levels of DNA methylation. (chinagene.cn)

While array-based approaches can identify large scale copy number variation (CNV), whole-genome sequencing (WGS) enables characterization of many complex SVs at base-pair resolution. (cancer.gov)
Until recently, real-time quantitative PCR (qPCR) assays and microarray hybridization have been the main methods used to determine copy number variation (CNV) in the genome. (bio-rad.com)
What Is Copy Number Variation? (bio-rad.com)
Copy number variation is defined as the presence of variable numbers of copies of a particular DNA segment relative to a reference genome. (bio-rad.com)
DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma. (cancercentrum.se)

Jan Korbel , Mechanisms of genomic structural variation in germline and cancer. (blogspot.com)
Here, we review current methods for breakpoint identification and their impact on the interpretation of chromosome aberrations in patients with MCA/MR. In addition, we discuss opportunities to dissect disease mechanisms based on large-scale genomic technologies and studies in model organisms. (biomedcentral.com)
The disorders are characterized by a defect in DNA repair mechanisms or genomic instability, and patients with these disorders show increased predisposition to cancer. (medscape.com)

Germline mutation of one TP53 allele is found in patients with Li-Fraumeni syndrome . (medscape.com)

Ways to abrogate heterogeneity will be required to optimise the genomic classification of tumours. (springer.com)
Not only has knowledge of the genomic landscape helped inform the development of new drugs, this understanding also promises to improve risk stratification of tumours and to determine their sensitivity to systemic therapies. (springer.com)

We study their DNA, RNA and protein content by genomic and proteomic approaches. (nibmg.ac.in)

At the time of progression, the clone with BCORL1 disappeared and the second clone acquired either additional PD-L1 3′ -UTR structural variations or a DDX3X p.R528C mutation. (yusukeokuno.com)
At the onset of blastic crisis, the clones with the additional PD-L1 3′-UTR structural variations acquired a DDX3X p.R528H mutation or a deletion affecting the DDX3X 3′ -UTR. (yusukeokuno.com)
Clonal duplication of a germline PTPN11 mutation due to acquired uniparental disomy in acute lymphoblastic leukemia blasts from a patient with Noonan syndrome. (lu.se)

Conclusions We reveal a Chlortetracycline Hydrochloride wealthy picture of germline variability and demonstrate what sort of one nucleotide polymorphism significantly affects the structure of the complete repertoire. (findadig.com)
Here we undertake a pilot study using the whole genome sequences from four Bangladeshi individuals, labelled samples S1, S6, S19 and S21, to gain an understanding of the functionally relevant single nucleotide variations (SNVs) that can occur in this population. (biomedcentral.com)

Numerous human genes encode potentially active DNA transposases or recombinases, but our understanding of their functions remains limited due to shortage of methods to profile their activities on endogenous genomic substrates. (biomedcentral.com)

Structural variation (SV) influences genome organization and contributes to human disease. (biomedcentral.com)
These data provide a foundational map of large SV in the morbid human genome and demonstrate a previously underappreciated abundance and diversity of cxSV that should be considered in genomic studies of human disease. (biomedcentral.com)
SVs can be inherited in the germline or acquired somatically, and have been implicated in a wide array of human diseases, including cancer. (cancer.gov)
Using negative and positive thioguanine resistance selection, combined with massively parallel DNA sequencing, we used HPRT1 screening to investigate the nuclease activity of PGBD5 on human genomic substrates. (biomedcentral.com)
In addition, participants will uncover the links between modalities of human genomics, neuronal electrophysiology, structural and functional neuroimaging, and observed behaviour that KCNI scientists are integrating through a series of virtual modules and a group-based project using real-world data types to study mental illness. (kcnischool.org)
Human variation datasets were obtained from the UCSC and NCBI repositories [ 4 , 5 ]. (biomedcentral.com)

Also in August, the Kids First study, Genomic analysis of a cohort with infantile hemangiomas associated with multi-organ structural birth defects , led by Dr. Dawn Siegel of the Medical College of Wisconsin was added. (kidsfirstdrc.org)
Biochemical, genomic, and structural analysis on protein complexes involved in cytokinesis in both Fission Yeast and mice to better understand the implications on health and disease. (uconn.edu)

There is therefore an urgent need for guiding references for sport and exercise genomics to allow the necessary advancements in this field of sport and exercise medicine, while protecting athletes from any invasion of privacy and misuse of their genomic information. (bmj.com)

The chromosomal loci encoding for the adjustable parts of TCRs and BCRs are complicated to decipher because of repetitive components and undocumented structural variations. (findadig.com)

Validation of the Clinical Use of GIScar, an Academic-developed Genomic Instability Score Predicting Sensitivity to Maintenance Olaparib for Ovarian Cancer. (cdc.gov)
This summer, the NIH Common Fund's Gabriella Miller Kids First Pediatric Research Program was pleased to announce the selection of a seventh set of childhood cancer and structural birth defect cohorts for whole genome sequencing. (kidsfirstdrc.org)

Structural variations are the main focus of Dr Korbel's research and he developed the paired-end mapping approaches , read depth , split reads , etc. (blogspot.com)
A subset of the inferences was noticed using individual genomic approaches also. (findadig.com)

Some insights into clinical risk factors and their genomic correlates have been made. (springer.com)

[ 2 ] The arachnoid cells have several proposed functions, including acting as a structural barrier with cellular wrapping/ensheathing, acting as a conduit for cerebrospinal fluid (CSF) drainage/absorption into dural sinuses/veins (arachnoid villi), epithelial-like/secretory functions, monocytelike functions, trophic support and byproduct detoxification for glial and neuronal cells, and participation in reactive/reparative processes. (medscape.com)

We propose a genomic signal processor framework that abstracts and transforms sequences and alignment entries into feature vectors such as read depth, split read depth, clipped read depth, supplemental read depth, strand bias, k-mer frequency and nucleic acid proportion. (uconn.edu)

The extent and impact of intra-species structural variation in complex repeat loci. (uconn.edu)

The panel's dimensions are contingent upon both the quantity of genes identified and the expanse of the genomic region they cover. (cd-genomics.com)

The rate of de novo structural variation is increased in in vitro-produced offspring and preferentially affects the paternal genome. (uliege.be)

The precise delineation of breakpoints by whole-genome sequencing enables the construction of local genomic architecture and facilitates the prediction of the molecular determinants of the patient's phenotype. (biomedcentral.com)

As a result, Bionano mapping yields hundreds of times more contiguous assembly than sequencing technologies alone can provide with unparalleled sensitivity for large structural variations (SVs) from 500 bp to mega base pair lengths. (mdanderson.org)
Impact of genomic structural variation in Drosophila melanogaster based on population-scale sequencing. (nature.com)

Anatomy1

Analytical, Diagnostic and Therapeutic Techniques and Equipment1

Phenomena and Processes6

Information Science2

Variants32

Mutations12

Somatic genomic1

Deletions7

Cancers3

High-throughput3

Tumor4

Whole exome1

Genomes4

Rearrangements6

Rare germline1

Transcriptomic2

Sequence8

Variant5

Genetic11

Rearrangement1

CNVs3

Copy number va5

Mechanisms3

TP531

Tumours2

Proteomic1

Mutation3

Nucleotide2

Methods1

Human6

Analysis2

Genomics1

Chromosomal1

Cancer2

Approaches2

Clinical1

Neuronal1

Sequences1

Loci1

Genes1

Novo1

Facilitates1

Sequencing2