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Results for “Chromosome Fragility”

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At least 343 records · Page 19Linked to original sources
PubMed1989

Analysis of chromosome breakage in the Prader-Labhart-Willi syndrome.

Analysis of chromosome breakage with mitomycin C (MMC) and folate-deficient culture conditions was undertaken on 18 Prader-Labhart-Willi syndrome (PLWS) patients (10 with 15q12 deletion [5 females, 5 males; mean age = 17.9 yr, range of 0.3 to 40 yr] and 8 without deletion [2 females, 6 males; mean age = 18.6 yr, range of 7 to 26 yr]), 21 PLWS parents with an average age of 39.2 yr and a range of 25 to 70 yr (12 fathers [8 fathers of PLWS children with the 15q12 deletion and 4 fathers of PLWS children with normal chromosomes] and 9 mothers [4 mothers of PLWS children with the 15q12 deletion and 5 mothers of PLWS children with normal chromosomes]), and age-matched control individuals. There was no difference between PLWS patients and control individuals in the number of chromosome and chromatid aberrations in cells grown at 48 and/or 96 hr in either 20 ng/ml or 50 ng/ml of MMC or between the PLWS parents and control individuals in cells grown in 50 ng/ml MMC for 96 hr, although a small increase (P less than 0.05) in chromosome breakage was found in cells from the total PLWS parental group compared with control individuals exposed for 48 hr in 50 ng/ml MMC. There was also no significant difference in chromosome fragile site frequency in cells grown in folate-deficient culture conditions in PLWS patients, their parents, or controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

[Cytogenetic analyses on giant cell tumor of bone].

Over a 3 year period, 19 surgically resected giant cell tumors of bone and cell lines from 4 cases were analysed cytogenetically. The results indicate that most of the tumor cells are heteroploid, the chromosome model number is predominantly hypodiploid. Karyotypic analysis demonstrated that the loss of chromosome #17, #18 appears more frequently (with a loss rate of 60% and 45% respectively), terminal deletion and telomeric fusion were the most common cytogenetic aberrations. We compared highly nonrandom tumor cell chromosome breakpoints and the same patient's somatic cell chromosome fragile sites with published oncogenes and found that 7q32, 13q13, 22q12 were coincident with MET, FLT, YES2/PDGFB (sis) respectively. Whether these loci abnormalities correlate with tumorgenesis needs further investigation.

Aneuploidy↗
PubMed1994

Fragile X founder chromosome effects: linkage disequilibrium or microsatellite heterogeneity?

Previous studies of founder chromosome effects in fragile X have been based on linkage disequilibrium with either FRAXAC1 or DXS548 alone or combined with FRAXAC2. Recently, we found no linkage disequilibrium of FMR-1 with FRAXAC2, but rather, found FRAXAC2 was complex and highly mutable. Therefore, we have now analyzed FRAXAC1 and DXS548 together for haplotypes, two markers which have not been jointly analyzed previously, to test for disequilibrium. We typed 315 fragile X (FX) chromosomes and controls, further subdivided into large controls (LC) and small controls (SC) with < or = 35 repeats and identified 26 different haplotypes. Two were more frequent and one less frequent in FX than SCs, thus confirming apparent linkage disequilibrium in fragile X. However, we noted increased FX microsatellite heterozygosity, either individually (results quite similar to previous studies) or as haplotypes. This heterozygosity covaried with FX > LC > SC, which may indicate alternative explanation exists for the apparent disequilibrium. We hypothesize that large FMR-1 CGG repeat allele genes may be associated with the generation of new microsatellite mutations. Possible mechanisms include gene conversions between CGG repeats and flanking microsatellites involving unequal double cross-overs, the expansion of small control CGGs to larger sizes associated with episodic generalized microsatellite instability or as a direct result of mutant FMR-1 gene function. We conclude that the founder effects observed with the use of these CA repeats is likely to reflect both linkage disequilibrium and increased microsatellite instability of fragile X chromosomes.

Alleles↗
PubMed1987

Children with the fragile X chromosome at schools for the mildly mentally retarded.

An investigation of children in schools for the moderately mentally handicapped in Coventry demonstrated that 29 of 259 children had a significant chromosomal abnormality. 10 of 155 boys (6 per cent) and 10 of 104 girls (10 per cent) had the fragile X syndrome. The clinical features which suggested this syndrome in males were IQ in the 50 to 70 range, head circumference greater than the 50th centile and post-pubertal testicular volume greater than the 50th centile. For both males and females, large ears were a useful sign. All children with fragile X had a carrier parent. The occurrence of mental retardation among sibs was one in two for brothers and one in four sisters. Considering all the males with fragile X syndrome resident in Coventry (this and previous studies), there were twice as many in schools for the moderately mentally handicapped as there were in schools for the severely mentally handicapped. There were as many females as males in the schools for the moderately mentally handicapped.

Cephalometry↗
PubMed2003

Chromosome arm 8p and cancer: a fragile hypothesis.

Chromosome arm 8p is one of the most frequently altered regions in human cancers. Several potential oncogenes and tumour suppressor genes have been identified but further investigations are needed to confirm which are bona fide oncogenic targets. In cancer cells, chromosome breaks may occur at fragile sites throughout the genome. Some fragile sites lie within genes that may have a role in cancer; the best example is FHIT at 3p14, which contains the fragile site FRA3B. We have found that chromosome breaks disrupt the NRG1 gene at 8p12 in breast and pancreatic cancers. We hypothesise that alteration of the NRG1 gene could occur through breakage at a non-common fragile site.

Acid Anhydride Hydrolases↗
PubMedDate not supplied

Genetic recombination in human melanoma and astrocytoma cell lines involves oncogenes and growth factor genes.

We describe here the chromosomal distribution of sister chromatid exchanges (SCEs) in four human tumor cell lines (two melanomas and two astrocytomas), and have mapped the sister chromatid recombination (SCR) sites. A higher incidence of SCR sites than expected on the basis of chromosome length occurred in chromosomes 2, 4, 5 and 15 in both the RPMI 5966 and MEL57 melanoma cell lines, and in chromosomes 1, 5, 13 and 15 of the IJKt and GUVW astrocytoma cell lines. A majority of the recombination sites occurred close to chromosomal fragile sites. A third of these occurred at the same bands as fragile sites. The recombination sites involved the N-ras and the epidermal growth factor gene in the melanomas. In the astrocytomas, the N-ras, Rb and c-mos genes appeared to be involved in the recombination events. The beta 2-microglobulin gene was involved in both astrocytomas and one melanoma. The erbB2 was involved in SCR only in the RPMI melanoma.

Astrocytoma↗
PubMed1997

Replacement of Fhit in cancer cells suppresses tumorigenicity.

The candidate tumor suppressor gene, FHIT, encompasses the common human chromosomal fragile site at 3p14.2, the hereditary renal cancer translocation breakpoint, and cancer cell homozygous deletions. Fhit hydrolyzes dinucleotide 5',5"'-P1,P3-triphosphate in vitro and mutation of a central histidine abolishes hydrolase activity. To study Fhit function, wild-type and mutant FHIT genes were transfected into cancer cell lines that lacked endogenous Fhit. No consistent effect of exogenous Fhit on growth in culture was observed, but Fhit and hydrolase "dead" Fhit mutant proteins suppressed tumorigenicity in nude mice, indicating that 5',5"'-P1, P3-triphosphate hydrolysis is not required for tumor suppression.

Acid Anhydride Hydrolases↗
PubMed1997

Additional clinical and cytogenetic findings associated with Rett syndrome.

An analysis of all aphidicolin-inducible breakpoints has been carried out in PHA stimulated T-lymphocytes of five patients with classical Rett syndrome, their mothers and a group of age matched controls. Observed breakpoints were divided into two groups: common, rare, and those recorded by others but not assigned as fragile sites by CCM92 and a group of non-specified breakpoints recurrently found in our ongoing study of fragile sites. In addition cooccurrence of trisomy X in one patient and de novo pericentromeric inversion on chromosome 2 in another Rett syndrome patient are reported. The co-occurrence with the Tourette syndrome in two of our families, and the fact that both Rett and Tourette syndrome are associated with movement disorders, possible dopaminergic hypersensitivity and increased chromosomal fragility in subsets of fragile sites, may suggest a possible avenue for further research. The cytogenetic findings indicate that both X-linked and autosomal regulatory region(s) may be part of a complex genetic alteration in association with Rett syndrome.

Aphidicolin↗
PubMed1999

[Dynamic mutation and its molecular cytogenetics].

Dynamic mutation, the mechanism of allelic expansion of the heritable unstable triplet repeat DNA sequences, has been the subject of intense investigation since its discovery in 1991 as the molecular basis for fragile X syndrome. The fundamental distinction between dynamic and other forms of mutation is that dynamic mutation is a process rather than a single event. The process involves a relationship between the copy number of perfect repeat DNA sequence and its instability which accounts for the anticipation seen in families carrying a dynamic mutation disease. Recently, dynamic mutation due to allelic expansion of minisatellite repeats has also been demonstrated as either the fragile sites and a genetic disease. In this minireview, dynamic mutations associated with chromosomal fragile sites and their cytogenetics are overviewed.

Chromosome Fragile Sites↗