Genomic instability (GIN) is a hallmark of cancer cells that facilitates the acquisition of mutations conferring aggressive or drug-resistant phenotypes during cancer evolution. Chromosomal instability (CIN) is a form of GIN that involves frequent cytogenetic changes leading to changes in chromosome copy number (aneuploidy). While both CIN and aneuploidy are common characteristics of cancer cells, their roles in tumor initiation and progression are unclear. On the one hand, CIN and aneuploidy are known to provide genetic variation to allow cells to adapt in changing environments such as nutrient fluctuations and hypoxia. Patients with constitutive aneuploidies are more susceptible to certain types of cancers, suggesting that changes in chromosome copy number could positively contribute to cancer evolution. On the other hand, chromosomal imbalances have been observed to have detrimental effects on cellular fitness and might trigger cell cycle arrest or apoptosis. Furthermore, mouse models for CIN have
Background: Aneuploidy, a karyotype deviating from multiples of a haploid chromosome set, affects the physiology of eukaryotes. In humans, aneuploidy is linked to pathological defects such as developmental abnormalities, mental retardation or cancer, but the underlying mechanisms remain elusive. There are many different types and origins of aneuploidy, but whether there is a uniform cellular response to aneuploidy in human cells has not been addressed so far. Results: Here we evaluate the transcription profiles of eleven trisomic and tetrasomic cell lines and two cell lines with complex aneuploid karyotypes. We identify a characteristic aneuploidy response pattern defined by upregulation of genes linked to endoplasmic reticulum, Golgi apparatus and lysosomes, and downregulation of DNA replication, transcription as well as ribosomes. Strikingly, complex aneuploidy elicits the same transcriptional changes as trisomy. To uncover the triggers of the response, we compared the profiles with ...
Aneuploidy can be either due to loss of one or more chromosomes or due to addition of one or more chromosomes. It leads to variation in number of chromosome
Aneuploidy is invariably associated with poor proliferation of primary cells, but the specific contributions of abnormal karyotypes to cancer, a disease characterized by aneuploidy and dysregulated proliferation, remain unclear. In this study, I demonstrate that the transcriptional alterations caused by aneuploidy in primary cells are also present in chromosomally unstable cancer cell lines, but the same alterations are not common to all aneuploid cancers. Chromosomally unstable cancer lines and aneuploid primary cells also share an increase in glycolytic and TCA cycle flux. The biological response to aneuploidy is associated with cellular stress and slow proliferation, and a 70-gene signature derived from primary aneuploid cells was defined as a strong predictor of increased survival in several cancers. Inversely, a transcriptional signature derived from clonal aneuploidy in tumors correlated with high mitotic activity and poor prognosis. Together, these findings suggested that there are two ...
Recombination between loxP sites with the same orientation in trans can generate ES cells with a deficiency accompanied by a duplication, regardless of the relative orientation of the two cassettes along a chromosome. The recombinant chromosomes will differ slightly, depending on the relative order of the Hprt cassettes. In one case, the chromosome with the deficiency will be tagged with the regenerated Hprt minigene, while the chromosome with the duplication will carry the neomycin- and puromycin-resistance cassettes. If the two cassettes are oppositely oriented, then the chromosome with the deficiency will carry the neomycin- and puromycin-resistance genes, and the chromosome with the duplication will carry the Hprt minigene.. The recombination frequency between loxP sites on the same chromosome appears to decrease as the distance between the loxP sites increases (Table 2). Similar observations have been reported in experiments in D. melanogaster using the FLP-FRT system (Golic and Golic ...
Egg infertility is a predisposition to miscarriages, infertility, and trisomic pregnancies caused by increased frequency of chromosome segregation errors in the eggs of women of advanced maternal age (AMA). Egg infertility is now a significant public health issue, with 1 in 5 US women now attempting her first pregnancy after age 35. Increased rates of egg infertility temporally coincide with rising levels of FSH that occur with age. By age 42, up to 87% of embryos are aneuploid, and 40-50% of women experience egg infertility. An Introductory Editorial will present an overview of causative factors and potential therapeutic strategies to prevent egg aneuploidy and infertility. Papers in series will be comprised of data drawn from studies performed both in animals and in humans. Part I will discuss endocrine and other molecular changes implicated in the pathogenesis of AMA oocyte aneuploidy and infertility. Section 1 will discuss defects that emerge with age in controlling the fidelity of meiotic oocyte
Mouse models of CIN. The most extensive evaluation of the role of aneuploidy in tumour formation stems from the analysis of mouse models with conditional or hypomorphic mutations in mitotic checkpoint genes [[10],[12],[14],[111],[112],[133],[134],[135],[136]]. Complete inactivation of the checkpoint early in embryogenesis leads to embryonic lethality, underscoring the essential role of the checkpoint in organism development. However, genetically engineered mice with an attenuated mitotic checkpoint are viable and display CIN and increased levels of aneuploidy in cells and tissues [[10],[12],[14],[111],[112],[133],[136],[137],[138],[139]]. Notably, as these animal models induce aneuploidy through continued CIN, the effect of aneuploidy in tumour development independently of CIN cannot be assessed. Several of these mice have increased spontaneous tumorigenesis, strongly supporting that CIN increases the probability of tumour formation ([[10],[110],[133],[139]]; for extensive reviews of the types ...
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This is a prospective, single-institution observational study to be conducted at 4 clinics within the Southern California Permanente Medical Group. Pregnant women who present for prenatal genetic counseling at the designated clinics and who meet study eligibility criteria will be offered the option of the verifi® prenatal test by a trained, licensed and certified genetic counselor (GC) . Women who elect the verifi® prenatal test will have a blood sample drawn by peripheral venipuncture that will be sent to the Verinata Health CAP-accredited clinical laboratory (Redwood City, CA). Results will be reported to the ordering health care provider by the laboratory within 8-10 business days and will be shared with the subject by their provider. Subject care and decision-making following NIPT result will be clinically managed by the provider with his/her subject and is not dictated by the study protocol. All eligible women who provide informed consent, whether they elect or decline NIPT will be asked ...
The primary outcome of this study is the false positive rate of fetal aneuploidy detection for chromosome 21, 18, and 13 by the Verinata Health Prenatal Aneuploidy Test and screen positive rate for fetal trisomy (T21) and trisomy (T18) by conventional prenatal screening methods. Birth outcomes, or karyotype if available, will be used as the reference standard ...
Chromosomal abnormalities are seen in nearly 1% of live born infants. We report a 5-year-old boy with the clinical features of Down syndrome, which is the most common human aneuploidy. Cytogenetic analysis showed a mosaicism for a double aneuploidy,
The cell cycle is a complex sequence of events through which a cell duplicates its contents and divides, and involves many regulatory proteins for proper cellular reproduction, including cyclin proteins and cyclin-dependent kinases, oncogenes and tumor-suppressor genes, and mitotic checkpoint protei …
1. Aneuploidy as the cause of cancer Cancer cells differ from normal in specific genotypes and phenotypes. The most common and massive cancer-specific genotype is aneuploidy, an abnormal number of chromosomes. The cancer-specific phenotypes include 1) dedifferentiation, 2) ability to metastasize, 3) constitutive genetic instability, 4) neoantigens, 5) metabolism, and 6) morphology. These cancer-specific properties are currently all interpreted as consequences of gene mutations. However, mutated genes do not typically generate new phenotypes, nor do mutated genes from cancer cells generate aneuploidy or transform diploid human or animal cells into cancer cells. In view of this we re-investigated the 100 year old hypothesis, that aneuploidy causes cancer. Confirming the aneuploidy hypothesis we have found, that each of 44 chemically transformed Chinese hamster cell colonies was aneuploid and all those tested were tumorigenic (Li et al., 1997). We propose that aneuploidy alters the cell - like ...
It has been known for more than half a century that the risk of conceiving a child with trisomy increases with advanced maternal age However the origin of the high susceptibility to nondisjunction of whole chromosomes and precocious separation of sister chromatids leading to aneuploidy in aged oocytes and embryos derived from them cannot be traced back to a single disturbance and mechanism Instead analysis of recombination patterns of meiotic chromosomes of spread oocytes from embryonal ovary and of origins and exchange patterns of extra chromosomes in trisomies as well as morphological and molecular studies of oocytes and somatic cells from young and aged females show chromosome specific risk patterns and cellular aberrations related to the chronological age of the female In addition analysis of the function of meiotic and cell cycle regulating genes in oogenesis and the study of the spindle and chromosomal status of maturing oocytes suggest that several events contribute synergistically to ...
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells? close ...
The advances in reproductive medicine have been many. As the New Year begins, here are FertilityAuthoritys four trends you should watch. Genetic screening of embryos for aneuploidy. A normal embryo has 23 pairs of chromosomes, including an XX or an XY to determine sex. Aneuploidy is the term used to describe an abnormal number of chromosomes, and majority of embryos with aneuploidy will not implant in the uterus or will result in a miscarriage. Many fertility clinics are now offering preimplantation genetic screening (PGS) for aneuploidy. One method that is gaining much attention is called comprehensive chromosomal analysis (CCS) tests a Day 5 or 6 embryo that is subsequently frozen and transferred during a frozen cycle. Women who have experienced recurrent miscarriages or recurrent IVF failure, or those who are of advanced maternal age, may want to ask their fertility doctors about PGS or CCS for aneuploidy screening.
Most human tumors have abnormal numbers of chromosomes, a condition known as aneuploidy. The mitotic checkpoint is an important mechanism that prevents aneuploidy by restraining the activity of the anaphase-promoting complex (APC). The deubiquitinase USP44 was identified as a key regulator of APC activation; however, the physiological importance of USP44 and its impact on cancer biology are unknown. To clarify the role of USP44 in mitosis, we engineered a mouse lacking Usp44. We found that USP44 regulated the mitotic checkpoint and prevented chromosome lagging. Mice lacking Usp44 were prone to the development of spontaneous tumors, particularly in the lungs. Additionally, USP44 was frequently downregulated in human lung cancer, and low expression correlated with a poor prognosis. USP44 inhibited chromosome segregation errors independent of its role in the mitotic checkpoint by regulating centrosome separation, positioning, and mitotic spindle geometry. These functions required direct binding to ...
STUDY QUESTION: Can next-generation sequencing (NGS) techniques be used reliably for comprehensive aneuploidy screening of human embryos from patients undergoing IVF treatments, with the purpose of identifying and selecting chromosomally normal embryos for transfer?. SUMMARY ANSWER: Extensive application of NGS in clinical preimplantation genetic screening (PGS) cycles demonstrates that this methodology is reliable, allowing identification and transfer of euploid embryos resulting in ongoing pregnancies.. WHAT IS KNOWN ALREADY: The effectiveness of PGS is dependent upon the biology of the early embryo and the limitations of the technology. Fluorescence in situ hybridization, used to test for a few chromosomes, has largely been superseded by microarray techniques that test all 24 chromosomes. Array comparative genomic hybridization (array-CGH) has been demonstrated to be an accurate PGS method and has become the de facto gold standard, but new techniques, such as NGS, continue to emerge.. STUDY ...
The study, which has also involved the collaboration of ICREA researcher Angel R. Nebreda, in the Oncologys programme at the same institute, explains how the molecular and cellular mechanisms triggered by aneuploid cells can give rise to tumours.. The research on aneuploidy and tumorigenesis has been performed using the wing primordia of the fruit fly Drosophila melanogaster as a model. This tissue is an epithelium organised into a single layer and that grows by 20 to 30,000 cells in a few days. Given these features, this tissue is an ideal system in which to generate genomic instability and to dissect the cell and molecular mechanisms that elicit aneuploid cells in a proliferating tissue.. Aneuploid cells: first step, suicide. The team of researchers observed that aneuploid cells first activate apoptosis (or programmed cell suicide). At the same time, in an attempt to counteract the imminent loss of cells, they send signals to neighbouring ones instructing them to divide and proliferate ...
InteGens Multiplex Interphase Chromosome Profiling products for Pre/Post-natal detect all common aneuploidies - 13, 18, 21, X and Y along with the option to detect all chromosomes and all common microdeletions. Whereas most prenatal diagnostic tests require an invasive procedure (CVS or amniocentesis), our FISH probes can be used on intact isolated/enriched fetal cells found in the mothers blood. This is made possible by our partner labs technology, which can recover 44 fetal cells from as little as 2ml of blood. This allows for a non-invasive blood test without putting the pregnancy at risk for miscarriage.. Most clinical labs that perform noninvasive prenatal testing (NIPT) test for all common aneuploidies (13, 18, 21, X and Y) and some claim they can test for the ten common microdeletions. However, if they find a positive result, labs must then provide further confirmation by invasive procedure. Combining our partners fetal cell isolation technology with InteGens innovative probes, labs ...
UniSA researchers at the Centre for Cancer Biology (CCB) have discovered a new aspect of cancer biology that may help to battle the spread and growth of tumours.. The research focuses on aneuploid cells, which are often associated with abnormal chromosome content and cell division - and how an enzyme known as caspase-2, initially discovered by the lead researcher 25 years ago, can act to prevent their growth.. Research leaders, Professor Sharad Kumar and Dr Loretta Dorstyn with PhD student Swati Dawar, have discovered that caspase-2, which is found in all mammals, has the capacity to suppress cancer growth by working to destroy aneuploid cells.. "Aneuploidy is a term that describes the abnormal chromosome content of a cell and occurs when there are failings during the normal division of a cell," Prof Kumar says.. "Aneuploidy is a feature of the majority of human tumours and is known to lead to chromosomal instability that can promote cancer onset and progression and cause drug ...
Defective segregation of chromosomes during cell division causes aneuploidy and is a characteristic feature of cancer cells. Cells therefore utilize multiple mechanisms to ensure faithful segregation and prevent aneuploidy, including phospho-regulation of proteins responsible for separating replicated chromosomes during mitosis. These mechanisms depend on the essential, conserved protein kinase Mps1. The goal of my work is to identify the downstream effectors of Mps1 in chromosome segregation and to illuminate the mechanisms of Mps1 function. This work will combine novel biochemical and cell biological approaches with emerging structural analysis methods to improve fundamental understanding of phospho-regulation of chromosome segregation.. ...
We have demonstrated that DANSR enables efficient and selective evaluation of cfDNA from maternal blood for fetal aneuploidy. We analyzed 298 plasma samples from pregnant women, including 39 T21 and seven T18 cases. Previous studies with MPSS have used a Z statistic cut-off of three standard deviations to classify cases as aneuploid or euploid.[7, 9] Using a similar statistical analysis, we correctly distinguished all aneuploid cases from average-risk cases using as few as 420 000 reads per sample.. Digital analysis of selected regions has several advantages compared with MPSS as an assay for aneuploidy. First, the fraction of raw sequencing reads that map to expected loci exceeds 96% with DANSR; by contrast, studies using MPSS report mapping rates of 20% to 50%.[7, 8] Second, DANSR produces sequence data only from chromosomes of clinical interest; by contrast, MPSS produces data from all chromosomes, irrespective of their relevance to analysis of aneuploidy. Taken together, the DANSR advantages ...
... On-line free medical diagnosis assistant. Ranked list of possible diseases from either several symptoms or a full patient history. A similarity measure between symptoms and diseases is provided.
The DNA microarray is a molecular genetic technique uses nucleic acid hybridization principle for gene expression studies, identification of genotype and mutations associated with the disease." After the discovery of…. ...
22q Moms...you are in need of some major relaxation and time for YOU. We are so excited to offer the first The 22q Family Foundation Moms Retreat: Finding YOU in the Midst of 22q. We will gather at the Spirit in the Desert Retreat Center in... ...
The chromosomal constitution of cells which deviate from the normal by the addition or subtraction of CHROMOSOMES, chromosome pairs, or chromosome fragments. In a normally diploid cell (DIPLOIDY) the loss of a chromosome pair is termed nullisomy (symbol: 2N-2), the loss of a single chromosome is MONOSOMY (symbol: 2N-1), the addition of a chromosome pair is tetrasomy (symbol: 2N+2), the addition of a single chromosome is TRISOMY (symbol: 2N+1 ...
In 1974, Segal and McCoy reported that primary foreskin fibroblasts of trisomy 21 patients proliferate more slowly than euploid control cells ( 6). Similar results were obtained from studies of primary mouse cells ( 7) or human cell lines ( 8) with decreased chromosome segregation fidelity. We set out to characterize the effects of a single extra chromosome on cell growth and proliferation in a systematic manner. This approach not only enabled us to determine whether every chromosome when present in an extra copy interferes with proliferation, but also allowed us to determine whether a general response to aneuploidy exists.. We established MEFs trisomic for either chromosome 1, 13, 16, or 19 using mice with balanced Robertsonian translocations. Analysis of the cell lines established from these aneuploid embryos revealed that cell proliferation was hampered in all trisomic MEFs compared with euploid controls. Furthermore, the characterization of the trisomic MEFs revealed a number of shared ...
... evolutionarily, provides been suggested as a factor in maintenance of chromosomal tumour and balance reductions. can either arise from different structural lesions, such simply because mutations, chromosomal translocations or deletions, or can result from statistical changes where cells lose or gain copies of entire chromosomes (aneuploidy).3 NVP-BEP800 As the most common chromosome abnormality in individuals, aneuploidy is the most common chromosome abnormality in individuals, is the trigger of many congenital delivery flaws and is found in the majority of good tumours.4 It is also regarded a key underlying factor to tumor onset and treatment. Aneuploidy occurs from extravagant mitotic occasions, including problems in centrosome quantity, kinetochore-microtubule accessories, spindle-assembly gate (SAC), chromosome telomeres or cohesion. 4 Aberrant mitotic police arrest systems normally result in cell loss of life by apoptosis, ...
Cytogenetic studies were performed in 95 adults with acute leukemia, 39 (41%) of whom had abnormal karyotypes in their leukemic cells. The karyotypes were grouped according to the Denver-Chicago classification, and abnormalities were correlated with clinical variables. The frequency and quality of abnormality was not influenced by age, morphologic type of leukemia, or prior treatment. The frequency of abnormal karyotypes was increased in patients with increasing leukocytosis. Hypodiploidy adversely affected response to treatment and survival. D or E group chromosome deletions were associated with a decreased response to treatment and survival, whereas patients with extra D or E chromosomes had an improved prognosis. The overall distribution of chromosomal abnormalities in the leukemic cells deviated significantly from the expected for random distribution. D+, E+, and G- abnormalities were significantly more frequent than expected. Patients with marrow leukemic cell aneuploidy showed a loss of ...
Most solid tumors are aneuploid, having a chromosome number that is not a multiple of the haploid number, and many frequently mis-segregate whole chromosomes ...
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If you have a question about this talk, please contact Kathy Oswald.. Hosts: Phil Zegerman & Meri Huch. Abstract not available. This talk is part of the Gurdon Institute Seminar Series series.. ...
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Dear Professor Winston, I would like some advice on a rare condition that I have been recently diagnosed with. I am in my mid-20s and have never experienced periods; there is no bleeding but I still get all other symptoms. I have always been very slim so the lack of periods was put down to my being underweight. After a considerable. Read More ...
A recent study demonstrates a high variability among different centers in the euploidy rate of embryos generated from donated eggs (Munnè et al., 2017). Using SNP array analysis, most embryonic meiotic aneuploidies have been found to be from maternal origin. From these observations, it may be speculated that the ovarian stimulation may affect the embryo euploidy rate independently from the oocyte source. Despite this, PGS in ED cycles is often considered unnecessary. Very few studies examined the use of PGS in ED cycles thus far and the results were inconclusive ...
A new study has demonstrated that an optimized method of comprehensive chromosomal screening (CCS) the first technology capable of accurate aneuploidy screening (screening of embryos for abnormal number of chromosomes) of all 24 chromosomes in just four hours.
In the pre-implantation embryo, aneuploidy resulting from chromosome segregation error is considered responsible for pregnancy loss. However, only a few studies have examined the relationship between chromosome segregation errors during early cleavage and development. Here, we evaluated this relationship by live-cell imaging using the histone H2B-mCherry probe and subsequent single blastocyst transfer using mouse embryos obtained by in vitro fertilization. We showed that some embryos exhibiting early chromosomal segregation error and formation of micronuclei retained their developmental potential; however, the error affected the blastocyst/arrest ratio. Further, single-cell sequencing after live-cell imaging revealed that all embryos exhibiting micronuclei formation during 1st mitosis showed aneuploidy at the 2-cell stage. These results suggest that early chromosome segregation error causing micronuclei formation affects ploidy and development to blastocyst but does not necessarily cause developmental
The cognitive deficits present in individuals with sex chromosome aneuploidies suggest that hemispheric differentiation of function is determined by an X-Y homologous gene [Crow (1993); Lancet 342:594-598]. In particular, females with Turners syndrome (TS) who have only one X-chromosome exhibit deficits of spatial ability whereas males with Klinefelters syndrome (KS) who possess a supernumerary X-chromosome are delayed in acquiring words. Since spatial and verbal abilities are generally associated with right and left hemispheric function, such deficits may relate to anomalies of cerebral asymmetry. We therefore applied a novel image analysis technique to investigate the relationship between sex chromosome dosage and structural brain asymmetry. Specifically, we tested Crows prediction that the magnitude of the brain torque (i.e., a combination of rightward frontal and leftward occipital asymmetry) would, as a function of sex chromosome dosage, be respectively decreased in TS women and increased in KS
RESULTS. Fluorescence in-situ hybridisation detected 558 (9.5%) patients with chromosomal abnormalities. Abnormal ultrasounds (70%) and maternal serum screens (21%) were the most indicative of chromosomal abnormalities. When comparing fluorescence in-situ hybridisation data with karyotype results for the five chromosomes of interest, the sensitivity and specificity were 99.3% and 99.9%, respectively. When comparing fluorescence in-situ hybridisation data with karyotype results for all chromosomes, the sensitivity decreased to 86.8%, whereas the specificity remained at 99.9%. Of 643 cases with karyotype abnormalities, 85 were fluorescence in-situ hybridisation-negative (false negative rate, 13.2%), which included structural rearrangements, chromosome mosaicism, and other trisomies. Despite abnormal ultrasound indications, fluorescence in-situ hybridisation missed 32 cases which included structural rearrangements, mosaicisms, and other trisomies ...
TY - JOUR. T1 - Rapid detection of aneuploidy following the generation of mutants in Candida albicans. AU - Lenardon, Megan D. AU - Nantel, André. PY - 2012. Y1 - 2012. N2 - Techniques used to generate mutants in Candida albicans commonly result in additional and undesired genetic rearrangements. Detection of aneuploidy is, therefore, an important step forward in the quality control of mutant phenotypes. In this chapter, we describe how to extract genomic DNA and perform a quantitative multiplex PCR to compare the karyotype of any mutant strain to that of its parent and allow the detection of any unwanted aneuploidy.. AB - Techniques used to generate mutants in Candida albicans commonly result in additional and undesired genetic rearrangements. Detection of aneuploidy is, therefore, an important step forward in the quality control of mutant phenotypes. In this chapter, we describe how to extract genomic DNA and perform a quantitative multiplex PCR to compare the karyotype of any mutant strain ...
Chromosomal aneuploidy is a common cause of birth defects. Unfortunately, the diagnostic sensitivity and specificity of current screening programs for fetal chromosomal aneuploidy have been unsatisfactory (1). The discovery of cell-free fetal DNA in maternal plasma (2) has led to the introduction of a new method of noninvasive fetal aneuploidy detection that uses next-generation sequencing (3-5). This method has been tested widely in clinical applications in recent years (6-8).. The current next-generation sequencing platforms have several weaknesses, however, and these limitations need to be addressed before these platforms can be used in routine clinical applications. These weaknesses include poor sample scalability, high cost, and a long sequencing time (2 to 3 days). A new benchtop sequencing instrument developed by Ion Torrent (owned by Life Technologies), based on semiconductor sequencing technology, can solve many of these problems (9, 10). The Ion Torrent Personal Genome Machine (PGM),6 ...
Aneuploidy is the gain or loss of individual chromosomes from the normal diploid set of forty-six chromosomes. As in structural anomalies, the error may be present in all cells of a person or in a percentage of cells. Changes in chromosome number generally have an even greater effect upon survival than changes in chromosome structure. Considered the most common type of clinically significant chromosome abnormality, it is always associated with physical and/or mental developmental problems. Most aneuploid patients have a trisomy of a particular chromosome. Monosomy, or the loss of a chromosome, is rarely seen in live births. The vast majority of monosomic embryos and fetuses are probably lost to spontaneous abortion during the very early stages of pregnancy. An exception is the loss of an X chromosome, which produces Turners syndrome. Trisomy may exist for any chromosome, but is rarely compatible with life.. Aneuploidy is believed to arise from a process called nondisjunction. Nondisjunction ...
Non-Invasive Prenatal Testing to detect chromosome aneuploidies in 57,204 pregnancies[25] "Non-invasive prenatal testing (NIPT) has been widely used to detect common fetal chromosome aneuploidies, such as trisomy 13, 18, and 21 (T13, T18, and T21), and has expanded to sex chromosome aneuploidies (SCAs) during recent years, but few studies have reported NIPT detection of rare fetal chromosome aneuploidies (RCAs). In this study, we evaluated the clinical practical performance of NIPT to analyze all 24 chromosome aneuploidies among 57,204 pregnancies in the Suzhou area of China. METHODS: This was a retrospective analysis of prospectively collected NIPT data from two next-generation sequencing (NGS) platforms (Illumina and Proton) obtained from The Affiliated Suzhou Hospital of Nanjing Medical University. NIPT results were validated by karyotyping or clinical follow-up. RESULTS: NIPT using the Illumina platform identified 586 positive cases; fetal karyotyping and follow-up results validated 178 T21 ...
Ulcerative colitis is a chronic inflammatory disease that mainly affects the colon and rectum. Onset of disease is most common between the ages of 15-35 years. There is an observed increased risk of colorectal cancer associated with the disease. The risk is often described to be 2% after 10 years, 8% after 20 years and 18% after 30 years disease.. Since 1977, all known patients with ulcerative colitis in the catchment area of Örnsköldsvik Hospital have been invited to attend a colonoscopic surveillance programme. At endpoint of the studies included in this thesis there were 214 patients that had attended the surveillance programme. The aims of these studies have been to evaluate the efficiency of the surveillance programme, analyse the impact of findings of DNA aneuploidy, and determine the outcome for patients that underwent limited resections instead of complete proctocolectomy. Further, we have studied the long-term outcome for patients who had an early onset of disease and analysed the ...
TY - JOUR. T1 - Reduced Chromosome Cohesion Measured by Interkinetochore Distance is Associated with Aneuploidy Even in Oocytes from Young Mice. AU - Merriman, Julie A.. AU - Lane, Simon I.R.. AU - Holt, Janet E.. AU - Jennings, Phoebe C.. AU - García-Higuera, Irene. AU - Moreno, Sergio. AU - McLaughlin, Eileen A.. AU - Jones, Keith T.. PY - 2013/2/1. Y1 - 2013/2/1. N2 - It is becoming clear that reduced chromosome cohesion is an important factor in the rise of maternal age-related aneuploidy. This reduction in cohesion has been observed both in human and mouse oocytes, and it can be measured directly by an increase with respect to maternal age in interkinetochore (iKT) distance between a sister chromatid pair. We have observed variations in iKT distance even in oocytes from young mice and wondered if such differences may predispose those oocytes displaying the greatest iKT distances to be becoming aneuploid. Therefore, we used two methods, one pharmacological (Aurora kinase inhibitor) and one ...
Many cancers have extremely high rates of chromosomal instability (CIN). Some cancers have chromosome segregation errors in every cell division, which would be detrimental to the growth of normal cells. Little is known about how cancers are able to thrive with high levels of CIN. We aim to determine how cells evolve to cope with CIN by creating a model system for persistent chromosomal instability in budding yeast. What types of mutations allow cells to adapt to a constantly shifting genomic content? What are the direct effects of CIN and aneuploidy on the health and viability of cells?. ...
Aneuploidy has been recognized as a hallmark of cancer for more than 100 years, yet no general theory has emerged to explain the recurring patterns of aneuploidy in cancer. Dr. Elledges laboratory developed the Tumor Suppressor and Oncogene (TUSON) Explorer, a computational method that analyzes the patterns of mutational signatures in tumors and predicts the likelihood that any individual gene functions as a tumor suppressor gene (TSG) or an oncogene (OG).
DNA aneuploidy has been identified as a prognostic factor for epithelial malignancies. Further understanding of the translation of DNA aneuploidy into protein expression will help to define novel biomarkers to improve therapies and prognosis. DNA ploidy was assessed by image cytometry. Comparison of gel-electrophoresis-based protein expression patterns of three diploid and four aneuploid colorectal cancer cell lines detected 64 ploidy-associated proteins. Proteins were identified by mass spectrometry and subjected to Ingenuity Pathway Analysis resulting in two overlapping high-ranked networks maintaining Cellular Assembly and Organization, Cell Cycle, and Cellular Growth and Proliferation. CAPZA1, TXNL1, and HDAC2 were significantly validated by Western blotting in cell lines and the latter two showed expression differences also in clinical samples using a tissue microarray of normal mucosa (n=19), diploid (n=31), and aneuploid (n=47) carcinomas. The results suggest that distinct protein ...