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Results for “Chromosome Fragility”

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At least 217 records · Page 12Linked to original sources
PubMed1993

Linkage disequilibrium between the fragile X mutation and two closely linked CA repeats suggests that fragile X chromosomes are derived from a small number of founder chromosomes.

In order to investigate the origin of mutations responsible for the fragile X syndrome, two polymorphic CA repeats, one at 10 kb (FRAXAC2) and the other at 150 kb (DXS548) from the mutation target, were analyzed in normal and fragile X chromosomes. Contrary to observations made in myotonic dystrophy, fragile X mutations were not strongly associated with a single allele at the marker loci. However, significant differences in allelic and haplotypic distributions were observed between normal and fragile X chromosomes, indicating that a limited number of primary events may have been at the origin of most present-day fragile X chromosomes in Caucasian populations. We propose a putative scheme with six founder chromosomes from which most of the observed fragile X-linked haplotypes can be derived directly or by a single event at one of the marker loci, either a change of one repeat unit or a recombination between DXS548 and the mutation target. Such founder chromosomes may have carried a number of CGG repeats in an upper-normal range, from which recurrent multistep expansion mutations have arisen.

Alleles↗
PubMed1987

[Chromosome instability observed in cells from monospermic, homozygous moles].

The present study was undertaken to disclose the mechanism which concerned to the propensity to malignancy of complete moles. For this purpose, the incidence of chromosomal aberrations and sister chromatid exchanges(SCE) after the administration of 0-30 ng/ml mitomycin C(MMC) were compared among cells cultured from molar and normal villi, and peripheral blood. Abnormally high induction of chromosomal aberrations and SCE was observed in molar cells without MMC treatment when compared with those of the remaining two cells. Then, higher susceptible responses to the low concentration of MMC were also noticeable in molar cells rather than two kinds of cells. As a result, it was assumed that chromosome instability possibly played an important role for choriocarcinogenesis of molar cells. Homozygosity of paternally derived genes may be responsible for this chromosome fragility. Six chromosomal bands (1q 21, 2p 24, 2p 13, 7q 31, 8q 22, 13q 33) were preferentially involved in the formation of chromosomal aberrations occurred spontaneously in molar cells. Four of these six bands were identical with the break points necessary for the production of the marker chromosomes in various tumors described previously, though one band was consistent with the N-myc oncogene locus. Thus, the possible association between chromosome rearrangements occurred in those six bands and the choriocarcinogenesis was assumed, though further accumulation of cytogenetic and molecular data was absolutely necessary.

Chromosome Aberrations↗
PubMed1982

Replication status of the fragile X chromosome, fra(X)(q27), in three heterozygous females.

Investigation of lymphocyte cultures from three females heterozygous for fra(X)(q27) shows widely differing proportions of early and late replicating X chromosomes having the fragile site, and suggests that the replication status of the fragile X may be related to the mental capacity of the patient. The study has utilised a sequential staining technique to reduce ascertainment bias, and evidence is presented to suggest that the expression of the fragile site is independent of the differential incorporation of BUdR into the early and late replicating X chromosomes.

Adult↗
PubMedDate not supplied

The prenatal detection of the fragile X chromosome: review of recent experience.

The fragile X chromosome has been identified in specimens from 17 male and 10 female fetuses in 11 laboratories throughout the world, obtained from at least 79 fetuses at increased risk for the fra(X) syndrome. Of these, 19 were confirmed, 6 were pending, 1 was negative and 1 could not be confirmed. Twenty-five of the 79 cases were studied in our laboratory (Institute for Basic Research [IBR]) and resulted in fra(X) demonstration in specimens from 3 male and 5 female fetuses. All 3 males and 2 of the 5 females have been confirmed. When amniocytes from the two confirmed female fetuses were exposed to FUdR after culturing in Chang medium, fra(X) frequencies were virtually negative indicating that Chang medium should not be used in fragile X studies at least when FUdR is used to induce fragility. Finally, amniocytes from a fra(X) male fetus studied in 3 different laboratories exhibited strikingly different frequencies. To date, we have experienced no false-positives or negatives, but the latter case was controversial. It is recommended that laboratories undertaking fra(X) prenatal detection use a combination of at least two different proven induction systems as well as complementary DNA marker studies to prevent false negative diagnosis.

Amniocentesis↗
PubMed2004

Common fragile genes.

Common chromosome fragile sites show susceptibility to DNA damage, leading to alterations that contribute to cancer development. The cloning and characterization of fragile sites have demonstrated that fragile sites are associated with genes that relate to tumorigenesis. Identification of the basis of instability at fragile sites and the related genes provides an entree to understanding of important aspects of chromosomal instability, a prominent feature of neoplastic genomes. FHIT/FRA3B and WWOX/FRA16D, the most sensitive common fragile genes in the human genome, function as tumor suppressor genes. The common features of these two common fragile genes are summarized, and suggest clues to understanding the relation between genomic instability and tumor biology.

Animals↗
PubMed1998

[DNA diagnosis of the fragile X chromosome syndrome--FRAXA using PCR].

BACKGROUND: Fragile X syndrome is gonosomal recessive mental retardation with the frequency 1:1000 in male population. Fragile X syndrome is caused by amplification of CGG repeat in 1. exon of FMT-1 gene. The aim of this study was to set up and validate a rapid and efficient PCR diagnosis to select FRAXA negative patients in population of mental retarded patients. METHODS AND RESULTS: In the set up phase of the method, 196 patients were diagnosed. We were using modified radioactive PCR of CGG. Obtained PCR fragments were separated on 6% denaturing PAGE. Results were correlated with Southern blot analysis using pE5.1 probe. STR-PCR was verified on a large set of patients and shows validity and efficiency of results in the case of pre- and full mutations in male hemizygous patients too. For estimation of carriers with pre- and full mutation by females modified diagnostic approach was developed. There was no difference found between results from PCR and Southern blot analysis. CONCLUSIONS: The PCR method is convenient not only for selection of FRAXA negative patients, but for diagnosis of full mutation and premutation of affected probands.

Chromosome Fragility↗
PubMed1983

Fragile X chromosome and chromosome condensation.

The effect of chromosome condensation on the frequency of expression of the fragile X chromosome was examined. Chromosome decondensation substances were tested for their ability to elicit expression or improve frequencies of expression of the fragile X chromosome in five patients. The substances tested included the AT specific DNA ligands ethidium bromide, Hoechst 33258, and netropsin, and the GC specific substances actinomycin D and olivomycin. Under culture conditions appropriate for eliciting fragile X expression none of the decondensation compounds studied significantly altered frequencies of expression, nor did any of the substances elicit fragile X expression under conditions that normally suppress fragile X expression. The fragile X was found to be more frequently evident in less condensed chromosome preparations from fibroblasts. The implications of these findings with respect to the nature of fragile sites are discussed.

Aged↗
PubMed1988

Chromosome breakage and recombination at fragile sites.

Chromosomal fragile sites are points on chromosomes that usually appear as nonstaining chromosome or chromatid gaps. It has frequently been suggested that fragile sites may be involved in chromosome breakage and recombination events. We and others have previously shown that fragile sites predispose to intrachromosomal recombination as measured by sister-chromatid exchanges. These findings suggested that fragile site expression often, if not always, is accompanied by DNA strand breakage. In the present report, fragile sites are shown to predispose to deletions and interchromosomal recombination. By use of somatic cell hybrids containing either human chromosome 3 or the fragile X chromosome, deletions and translocations were induced by FUdR or aphidicolin with breakpoints at the fragile sites Xq27 or 3p14.2 (FRA3B) or at points so close to the fragile sites as to be cytogenetically indistinguishable. Southern blot analysis of DNA from a panel of chromosome 3 deletion and translocation hybrids was then utilized to detect loss or retention of markers flanking FRA3B and to corroborate the cytogenetic evidence that the breakpoints were at this fragile site. One cell line with a reciprocal translocation between human chromosome 3 (with breakpoint at 3p14.2) and a hamster chromosome showed cytogenetically that the fragile site was expressed on both derivative chromosomes, supporting the hypothesis that the fragile site represents a repeated sequence. The approach described provides a means of generating specific rearrangements in somatic cell hybrids with a breakpoint at a fragile site.(ABSTRACT TRUNCATED AT 250 WORDS)

Aphidicolin↗
PubMed1981

Familial X-linked mental retardation and fragile X chromosomes in two Swedish families.

X-linked mental retardation (MR) associated with a fragile X chromosome was found in two Swedish families. The fragile X chromosome was demonstrated in 5/5 boys with mental retardation. Clinical data on four of these boys are presented. In one of the families, the mental retardation was associated with macro-orchidism, large hands and large, folded ears. In the other family, macro-orchidism was not seen, possible because the boys were younger. Fragile site X chromosomes were also seen in three obligate carriers. A summary of earlier published cases of X-linked MR associated with the fragile X chromosome is given.

Abnormalities, Multiple↗
PubMed1987

Fragile sites, chromosome evolution, and human neoplasia.

In a study of the possible relationship between human fragile sites, chromosomal rearrangements related to neoplasia, and chromosome regions involved in evolutionary changes, we have found that 17 fragile sites related to cancer, 15 fragile sites not related to cancer, and 17 non-fragile regions also related to human malignancy correspond or are close to bands involved in rearrangements that have taken place during chromosomal evolution in primates.

Animals↗
PubMed1983

Familial fragility on chromosome 16 (fra 16q22) enhanced by both interferon and Distamycin A.

A family with a "fragile site" at 16q22, inducible by both interferon and Distamycin A, is reported. Immunological problems were found in the family. In a sibship of ten, eight children had died in infancy. Our study led to the conclusions that interferon and Distamycin A induce fragility at the same site, which has the same characteristics as the spontaneous fragile site; that a viral hypothesis for this fragility may be supported; and that immunoincompetence of one kind or another must be considered in families presenting a fragile site at 16q22.

Adult↗
PubMed2000

Analysis of replication timing at the FRA10B and FRA16B fragile site loci.

The molecular basis for the cytogenetic appearance of chromosomal fragile sites is not yet understood. Late replication and further delay of replication at fragile sites expressing alleles has been observed for FRAXA, FRAXE and FRA3B fragile site loci. We analysed the timing of replication at the FRA10B and FRA16B loci to determine whether late replication is a feature which is shared by all fragile sites and, therefore, is a necessary condition for chromosomal fragile site expression. The FRA10B locus was located in a transitional region between early and late zones of replication. Fragile and non-fragile alleles exhibit a similar replication pattern proximal to the repeat but fragile alleles are delayed relative to non-fragile ones on the distal side. Although fragility at FRA10B appears to be caused by expansion of an AT-rich repeat in the region, replication time near the repeat was similar in fragile and non-fragile alleles. The FRA16B locus was late replicating and appeared to replicate even later on fragile chromosomes. While these observations are compatible with the hypothesis that delayed replication may play a role in fragile site expression, they suggest that replication delay may not need to occur at the expanded repeat region itself in order to be permissive for fragility.

Alleles↗
PubMed1983

Tables for the cytogenetic study of fragile X chromosomes for diagnostic purposes.

The frequency of expression of the fragile X chromosome varies from patient to patient. Many cases have been reported showing frequencies of less than 2%. With such low frequencies, the risk of erroneous diagnosis is great unless the appropriate number of cells is studied. We present here Tables based on the binomial distribution relating the frequency of expression of the fragile X in a patient with the sample size required to obtain a probability P of correct diagnosis according to different criteria.

Chromosome Fragility↗
PubMedDate not supplied

Cytogenetic studies of males with schizophrenia. Screening for the fragile X chromosome and other chromosomal abnormalities.

Genetic factors appear to play a role in the etiology of schizophrenia, although no specific genetic mechanism has yet been identified. As a preliminary measure in the search for the chromosomal location of a gene or genes relevant to this illness, cytogenetic screening of populations of patients might provide clues for further in depth molecular studies. Additionally, since the X chromosome has been implicated as a possible site, specific examinations aimed at identifying abnormalities in this chromosome including the presence of the fragile X site, could also be important. The following report reviews the previous literature on chromosomal aberrations in schizophrenia and presents data from a new survey of 46 unrelated male patients with schizophrenia. No chromosomal aberrations or folate-sensitive fragile sites were found in samples from these patients.

Adult↗
PubMed1992

[Clinico-electrophysiological characteristics of women--heterozygote carriers of fragile X chromosome].

Overall 21 women, heterozygous carriers of fragile X-chromosome (7 cases of obligate carriership and 14 sporadic cases) were examined by electroencephalography and cytogenetically. In none of them the clinical examination revealed a typical somatic appearance characteristic of Martin-Bell syndrome. Certain somatic disorders, psychasthenic traits, tearfulness and uncommunicativeness were recorded in single cases. The level of intellectual development corresponded to the low norm. Analysis of the EEG has demonstrated that in 76% of the women examined, the character of alpha-rhythm differed from normal. According to its intensity, three variants of the EEG were distinguished. In the majority of women, the EEG manifested the signs of the dysfunction of the diencephalic structures and not gross focal alterations. The character of the EEG does not provide any data which may be of diagnostic importance in revealing heterozygous carriership of fragile X-chromosome.

Action Potentials↗