Genomic fragile sites. Medical search. Frequent questions

Late-replication may be a result of formation of non-B DNA structures like hairpins and toroids that stall the replication fork in AT rich regions, analogous to the proposed mechanism of rare fragile site instability. (wikipedia.org)
High speed of fork progression induces DNA replication stress and genomic instability. (nature.com)
2 In addition, hypoxia induces genetic instability by the induction of fragile sites causing gene amplification. (bmj.com)
[ 4 ] In vivo aging is linked with accelerated aging of fibroblasts in culture, possibly due to the genomic instability, a hallmark of WS. (medscape.com)
Further functional analyses revealed increased genomic instability upon replication stress, as represented by mitotic bulky and ultrafine DNA bridges. (rug.nl)
Together, our data uncover a role for H3.3 in DNA replication under stress conditions that is altered by the K27M mutation, promoting genomic instability and potentially glioma development. (rug.nl)
Yet whereas most research is directed at understanding the role of mutant H3 in deregulating gene expression, we studied if and how it contributes to genomic instability-a research avenue that remains mostly unexplored. (rug.nl)
In past due era mice and derivative cells, there is certainly improved genomic preservation and instability of p53-mediated senescence and apoptosis, resulting in serious cells degeneration and atrophy, premature ageing, and suppression of cancer compared with controls. (woofahs.com)
A recent study demonstrated the molecular basis of tetraploidization by deprotected telomeres in the absence of Pot1 and p53, further implicating dysfunctional telomeres as a cause of genomic instability in human cancer [16]. (woofahs.com)
Despite the large body of well-described biological outcomes, the molecular mechanisms underlying the role of p53 in suppressing the genomic instability associated with telomere dysfunction are not well understood. (woofahs.com)
Genomic instability is a hallmark of cancer. (alquds.edu)
These recurrent homozygous deletions occur either over tumour suppressors or over fragile sites, regions of increased genomic instability. (ox.ac.uk)
However, it can also occur in regions of increased genomic instability (fragile sites). (ous-research.no)
Double strand break (DSB) repair mechanisms guard genome integrity and their deterioration causes genomic instability. (iegt-rostock.de)
Common and rare fragile sites (CFS and RFS, respectively) are particularly vulnerable to instability, and there is an inverse correlation between fragile site (FS) expression and DSB repair protein levels. (iegt-rostock.de)
Large replicons are difficult to duplicate and strongly associated with fragile sites and other forms of genomic instability. (grantome.com)
A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome? (psu.edu)
Dive into the research topics of 'A genome-wide analysis of common fragile sites: What features determine chromosomal instability in the human genome? (psu.edu)
A genome-wide increase in chromosome instability (gains and losses) within genes and at chromosome fragile sites was observed, resulting in changes to gene-expression profiles. (bvsalud.org)
In the absence of Senataxin, the Cockayne syndrome protein CSB was required for the recruitment of the transcription-coupled repair endonucleases (XPG and XPF) and RAD52 recombination protein to target and resolve transcription bubbles containing R-loops, leading to genomic instability. (bvsalud.org)
The human papillomavirus type 16 E6 and E7 oncoproteins cooperate to induce mitotic defects and genomic instability by uncoupling centrosome duplication from the cell division cycle. (virosin.org)
Thus, our work provides a mechanism for how tumor-predisposing BRCA2 inactivation links transcription-induced DNA damage with mitotic DNA repair to fuel the genomic instability characteristic of cancer cells. (ox.ac.uk)

Our study identified ZNF365 as a necessary target whose activation by p53 in the presence of critically short telomeres contributes to genomic stability. (woofahs.com)

High frequency of deletions at breakpoints within these fragile sites has been associated with many cancers, including breast, lung, and gastric cancers (for review, see ) MicroRNA genes, which are preferentially involved in chromosomal alterations, are frequently located at fragile sites. (wikipedia.org)
Loss of BRCA1 or BRCA2 markedly increases the rate of base substitution mutagenesis and has distinct effects on genomic deletions. (nature.com)
Our analysis defines 96 genomic regions recurrently targeted by homozygous deletions. (ox.ac.uk)
We construct a statistical model that separates fragile sites from regions showing signatures of positive selection for homozygous deletions and identify candidate tumour suppressors within those regions. (ox.ac.uk)
They were able to separate the regions with positive selection for homozygous deletions from the fragile sites, and found 16 established tumour suppressors as well as 27 candidate tumour suppressors. (ous-research.no)
Rarely, small deletions of genetic material from the AFF2 gene are associated with fragile XE syndrome, although how these deletions affect the protein and lead to intellectual disability is unknown. (medlineplus.gov)

Clinically, the most important rare fragile site is FRAXA in the FMR1 gene, which is associated with the fragile X syndrome, the most common cause of hereditary intellectual disability. (wikipedia.org)
The FRAXA site is perhaps most famous for its role in Fragile X syndrome, but fragile sites are clinically implicated in many other important diseases, such as cancer. (wikipedia.org)
To investigate the prevalence of fragile X syndrome (FXS) in intellectually disabled male and female Indonesians. (wjgnet.com)
We show that such miRNAs over-accumulate in RFS, and that FRAXA, which is expressed in Fragile X syndrome, is a conserved hotspot for miRNAs inhibiting DSB repair. (iegt-rostock.de)
This project investigates several aspects of DNA methylation and replication related to fragile X syndrome. (grantome.com)
Stone WL, Basit H, Los E. Fragile X Syndrome. (medscape.com)
Fragile X syndrome: a review of associated medical problems. (medscape.com)
Lachiewicz AM, Dawson DV, Spiridigliozzi GA. Physical characteristics of young boys with fragile X syndrome: reasons for difficulties in making a diagnosis in young males. (medscape.com)
AGG interruptions within the maternal FMR1 gene reduce the risk of offspring with fragile X syndrome. (medscape.com)
Murphy MM. A review of mathematical learning disabilities in children with fragile X syndrome. (medscape.com)
Del Hoyo Soriano L, Thurman AJ, Harvey DJ, Ted Brown W, Abbeduto L. Genetic and maternal predictors of cognitive and behavioral trajectories in females with fragile X syndrome. (medscape.com)
Bailey DB Jr, Raspa M, Bishop E, Holiday D. No change in the age of diagnosis for fragile x syndrome: findings from a national parent survey. (medscape.com)
Reisinger DL, Shaffer RC, Tartaglia N, Berry-Kravis E, Erickson CA. Delineating Repetitive Behavior Profiles across the Lifespan in Fragile X Syndrome. (medscape.com)
Advances in the treatment of fragile X syndrome. (medscape.com)
The fragile X syndrome: no evidence for any recent mutations. (medscape.com)
Profiles of aberrant white matter microstructure in fragile X syndrome. (medscape.com)
Health supervision for children with fragile x syndrome. (medscape.com)
A Randomized Double-Blind, Placebo-Controlled Trial of Minocycline in Children and Adolescents with Fragile X Syndrome. (medscape.com)
Mutations in the AFF2 gene cause fragile XE syndrome, a condition characterized by mild intellectual disability and learning difficulties. (medlineplus.gov)
In North Carolina, 25,000 newborns took part in the Early Check study, a neonatal genetic screening project focusing on childhood spinal muscular atrophy , fragile X syndrome , and Duchenne muscular dystrophy . (medscape.com)
The association between mosaicism type and cognitive and behavioral functioning among males with fragile X syndrome. (cdc.gov)
Preventive care services and health behaviors in children with fragile X syndrome. (cdc.gov)
FORWARD: A Registry and Longitudinal Clinical Database to Study Fragile X Syndrome. (cdc.gov)
Autism Spectrum Disorder in Fragile X Syndrome: Cooccurring Conditions and Current Treatment. (cdc.gov)
Fragile X Syndrome: Scientific Background and Screening Technologies. (cdc.gov)
Molecular genetic testing for fragile X syndrome: laboratory performance on the College of American Pathologists proficiency surveys (2001-2009). (cdc.gov)
By closely examining models of three disorders with established genetic associations to repeats - Fragile X syndrome, X-linked Dystonia Parkinsonism, and MORC2-syndromes - the researchers hope to uncover common themes and mechanisms that underpin how repetitive elements contribute to the development of brain disorders. (lu.se)

A chromosomal fragile site is a specific heritable point on a chromosome that tends to form a gap or constriction and may tend to break when the cell is exposed to partial replication stress. (wikipedia.org)
Common chromosomal fragile sites (CFSs) are genomic regions prone to form breaks and gaps on metaphase chromosomes during conditions of replication stress. (ku.dk)
Chromosomal common fragile sites (CFSs) are unstable genomic regions that break under replication stress and are involved in structural variation. (psu.edu)

Aqeilan, RI 2014, ' Role of common fragile sites and corresponding genes in cancer development ', Cellular and Molecular Life Sciences , vol. 71, no. 23, pp. 4487-4488. (huji.ac.il)
Upon DSB repair dysfunction, genes residing at these sites are at greater risk of deregulation compared to genes located at non-FS. (iegt-rostock.de)
Through a series of elegant experiments including co-localization of Rad9 with the transcription factor Aft1, expression profiling upon Rad9 deletion and genome-wide localization of Rad9, Christos showed that Rad9 also plays a surveillance role in the yeast genome, being preferentially stationed at "high-risk" regions, such as highly expressed genes, sites of origin of replication and recombination hotspots. (weebly.com)
Over 50% of miRNAs genes are located in cancer-associated genomic regions or fragile sites, and have been found to be involved in carcinogenesis as tumor suppressors or oncogenes [ 8 , 9 ]. (oncotarget.com)
Although the evolutionary history of the caveolin genes has not been clearly defined, there are clues within their sequences and genomic organization to suggest possible mechanisms for their origin. (biomedcentral.com)

Unlike RFSs, common fragile sites (CFSs) are not the result of nucleotide repeat expansion mutations. (wikipedia.org)
Newly available genome-wide profiling studies provide us with an unprecedented opportunity to associate CFSs with features of their local genomic contexts. (psu.edu)
Here, we contrasted the genomic landscape of cytogenetically defined aphidicolin-induced CFSs (aCFSs) to that of nonfragile sites, using multiple logistic regression. (psu.edu)

High-resolution profiling revealed that these sites are different from MiDAS at aphidicolin-induced common fragile sites in that they map to genomic regions replicating in the early S-phase, which are close to early-firing replication origins, are highly transcribed, and display R-loop-forming potential. (ox.ac.uk)

I will also assess whether a protein known to recognize and bind to spots of DNA damage can protect dividing B cells from genomic rearrangements at these sites-work that could point toward novel therapies for cancers that develop in the cells of the immune system. (pewtrusts.org)
This gene spans the second most common chromosomal fragile site, FRA16D and as consequence is frequently affected by genomic abnormalities and chromosomal rearrangements. (mdanderson.org)
They frequently are sites of chromosomal rearrangements in cancer and of viral integration. (psu.edu)
Importantly, the MiDAS sites identified in BRCA2-deficient cells also represent hotspots for genomic rearrangements in BRCA2-mutated breast tumors. (ox.ac.uk)
8] A paper from 2010 reported 18 new mutations, including 2 genomic rearrangements, a deep intronic mutation resulting in a novel exon, a splice consensus mutation leading to utilization of the nearby splice site, and 2 rare missense mutations. (medscape.com)

Here, we identify genome-wide the sites where MiDAS reactions occur when BRCA2 is abrogated. (ox.ac.uk)
CG2's contribution in this work was primarily related to the analysis of primary data, the extraction of genome-wide profiles of protein binding from ChIP-on-chip experiments and the statistical inference of genomic co-localizations. (weebly.com)

Sites FRA3B (harboring the FHIT gene) and FRA16D (harboring the WWOX gene) are two well known examples and have been a major focus of research. (wikipedia.org)
The WW domaincontaining oxidoreductase (WWOX) is a tumor suppressor spanning the common chromosomal fragile site FRA16D. (alquds.edu)

Of relevance to our study, such genomic fragile sites include telomeres that are particularly sensitive to replication blockade [4, 6]. (woofahs.com)

Common fragile sites are considered part of normal chromosome structure and are present in all (or nearly all) individuals in a population. (wikipedia.org)
This observation cells into question the traditional concept of a gap (G2) between DNA replication and chromosome condensation for mitosis, and it may explain sites of chromosome fragility. (grantome.com)
Evidence was recently presented of a crucial role for a helicase in protecting cells against chromosome breakage at normally occurring replication fork-stalling sites. (medscape.com)

Rare fragile sites are found in less than 5% of the population, and are often composed of two- or three-nucleotide repeats. (wikipedia.org)
For a database of fragile sites in human chromosomes, see Rare fragile sites (RFSs) are classified into two sub-groups based on the compounds that elicit breakage: folate-sensitive groups (for examples, see ), and nonfolate-sensitive groups, which are induced by bromodeoxyuridine (BrdU) or distamycin A, an antibiotic that preferentially binds to AT-pairs of DNA. (wikipedia.org)

DNA replication, as determined by BrdU incorporation in cells by sorted by DNA content and cyclin B1 staining, occurs quite late in the cell cycle, within 90 minutes of mitosis for FMR1 and as much as 1% of total genomic DNA. (grantome.com)

Hier de conclusie van deze review en daaronder een studie abstract met ranpirnasse uit 2002 met bijzonder goede resultaten op de mediane overlevingstijd. (kanker-actueel.nl)

In the mammalian genome, certain genomic loci/regions pose greater challenges to the DNA replication machinery (i.e., the replisome) than others. (elsevierpure.com)
Investigating the mechanisms by which Smc5/6 and Rtt107 facilitate large replicon synthesis will broaden our understanding of the maintenance of high-risk genomic regions. (grantome.com)
We show that local genomic features are effective predictors both of regions harboring aCFSs (explaining ∼77% of the deviance in logistic regression models) and of aCFS breakage frequencies (explaining ∼45% of the variance in standard regression models). (psu.edu)
10] Fragile sites may be DNA regions particularly sensitive to replicative stress. (medscape.com)

Each newborn will receive whole-genome sequencing (WGS) and targeted genomic sequencing (TGS) - which will use a multiplexed panel being developed with Quest Diagnostics - to identify any of more than 1,700 genetic disorders. (genomeweb.com)
For example, genetic testing can provide a diagnosis for a genetic condition such as Fragile X or information about your risk to develop cancer. (cdc.gov)
Large-scale genomic testing is also used in research to learn more about the genetic causes of conditions. (cdc.gov)

Under normal conditions, most common fragile sites are not prone to spontaneous breaks. (wikipedia.org)
Common fragile sites are of interest in cancer studies because they are frequently affected in cancer and they can be found in healthy individuals. (wikipedia.org)
Exposure of lymphoblastoid cells to WTC particulate matter led to dysregulation of DNA replication at common fragile sites in vitro. (nature.com)
FANCD2 facilitates replication through common fragile sites. (nature.com)
2014. Are common fragile sites merely structural domains or highly organized "functional" units susceptible to oncogenic stress? (virosin.org)

We hope this innovative precision medicine approach to diagnosis and treatment of fragile newborns allows us to care for these infants in a faster, cheaper, and better way. (genomeweb.com)

The FRAXE site is associated in the development of a form of mental retardation without any distinctive phenotypic features. (wikipedia.org)
Since FXS cannot always be identified by cytogenetic analysis, molecular testing of the fragile X mental retardation 1 CGG repeat was performed in 440 samples. (wjgnet.com)
Hillman MA, Gecz J. Fragile XE-associated familial mental retardation protein 2 (FMR2) acts as a potent transcription activator. (medlineplus.gov)

I will stimulate the rapid division of B cells and identify the "fragile sites" within the genome that are prone to breaks and rearrangement. (pewtrusts.org)

Together, these total results support the view that ZNF365 is a novel player adding to genomic stability. (woofahs.com)

Additionally, the Hepatitis B virus (HBV) and HPV-16 virus, the strain of human papilloma virus most likely to produce cancer, appear to integrate preferentially in or around fragile sites, and it has been proposed that this is crucial to the development of tumors. (wikipedia.org)

Fragile Females: Case Series of Epilepsy in Girls With FMR1 Disruption. (medscape.com)

Maintaining genomic integrity is of utmost importance to eukaryotic cells, which have evolved sophisticated mechanisms to ensure speed, accuracy, and an adequate pool of nucleotide and replication factors as well as high-fidelity repair pathways to correct errors occurring during DNA replication. (bmj.com)
Importantly, the genomic features we identified here as significant predictors of fragility allow us to draw valuable inferences on the molecular mechanisms underlying aCFSs. (psu.edu)

Outcomes p53 reactivation in cells with telomere dysfunction causes powerful gene manifestation adjustments resembling a mobile checkpoint response To define the p53-mediated transcriptome MSH6 connected with telomere dysfunction, we used a era 4 telomerase-negative, Atm-negative (G4 (triple knockout, TKO) pores and skin fibroblasts display inactivation of mobile checkpoints offering genomic balance. (woofahs.com)

To date, more than 120 fragile sites have been identified in the human genome. (wikipedia.org)
To identify the causal defect in AOA2, patient-derived cells and SETX knockouts (human and mouse) were analyzed using integrated genomic and transcriptomic approaches. (bvsalud.org)
Researchers in Human Genetics and Genomics Advances report that how researchers describe genomic studies may alienate potential participants. (genomeweb.com)
Both are fragile substrates where careless human intervention can cause more harm than good. (nationalacademies.org)
Christopher Douse explores the repetitive portion of the human genome, so-called 'genomic dark matter', and its role in human brain development and degeneration. (lu.se)
This award includes a $1.2 million grant to support his lab's exploration of the repetitive portion of the human genome, so-called 'genomic dark matter', and its role in human brain development and degeneration. (lu.se)

In alternative models, CpG island density, transcription start site density, H3K4me1 coverage, and mononucleotide microsatellite coverage are significant predictors. (psu.edu)
The degree of methylation varies, however, with some sites (apparently binding sites for transcription factors) less methylated than others. (grantome.com)

Any obstacles encountered by cells in this process can lead to 'replicative stress' ( Figure 1 ), 1 which may be overcome by replicative stress response proteins, but deficiencies in this response result in accumulated errors in DNA replication and loss of genomic integrity, which lead to cell death. (bmj.com)

Our work in collaboration with the lab of Despoina Alexandraki from the Dept of Biology at the University of Crete and IMBB-FORTH, entitled "Rad9 interacts with Aft1 to facilitate genome surveillance in fragile genomic sites under non-DNA damage-inducing conditions in S. cerevisiae " was published last week in Nucleic Acids Research. (weebly.com)

Spath MA, Feuth TB, Smits AP, Yntema HG, Braat DD, Thomas CM. Predictors and risk model development for menopausal age in fragile X premutation carriers. (medscape.com)

We also analyzed aCFS breakage frequencies as a function of their genomic landscape, using standard multiple regression. (psu.edu)

In addition to TMC, study sites include Rady Children's Institute for Genomic Medicine, Mt. Sinai Hospital, University of North Carolina-Chapel Hill, Cincinnati Children's Hospital, and the University of Pittsburgh. (genomeweb.com)

Newborn, carrier, and early childhood screening recommendations for fragile x. (medscape.com)

Graph theory analysis of genomic problems: community analysis of fragile sites correlations and of pseudogenes alignments: Re A, Molineris I, Caselle M. (linkgroup.hu)
Bannoehr J, Zakour NL, Reglinski M, Inglis N: Genomic and surface proteomic analysis of the canine pathogen Staphylococcus pseudintermedius reveals protein that mediate adherence to the extracellular matrix. (srcpathway.com)

Anatomy10

Organisms3

Diseases13

Chemicals and Drugs10

Analytical, Diagnostic and Therapeutic Techniques and Equipment13

Psychiatry and Psychology1

Phenomena and Processes49

Disciplines and Occupations2

Technology, Industry, Agriculture1

Information Science5

Instability22

Contributes to genomic stability1

Deletions6

Syndrome27

Replication stress3

Genes5

CFSs3

Aphidicolin-induced1

Rearrangements5

Genome-wide2

FRA16D2

Telomeres1

Chromosome3

Rare fragile2

Mitosis1

Abstract1

Regions4

Genetic3

Common5

Treatment of fragile1

Mental retardation3

Prone1

ZNF3651

Tumors1

FMR11

Mechanisms2

Outcomes1

Human6

Transcription2

Integrity1

Facilitate1

Predictors1

Breakage1

Include1

Newborn1

Analysis2