Detection of Breakpoints in Submicroscopic Chromosomal Translocation, Illustrating an Important Mechanism for Genetic Disease

Lamb, Janette; Harris, Peter C.; Lindenbaum, R H; Reeders, Stephen T.; Wilkie, Andrew O.M.; Buckle, Veronica J.; Barton, N.J.; Weatherall, D. J.; Higgs, Douglas R.

doi:10.1016/s0140-6736(89)92995-4

Cited by 71 publications

(37 citation statements)

References 22 publications

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“…Table 2 contains a list of all reported derivative chromosomes involving 1p36 that resulted in deletion. 24,26,[34][35][36][37][38][39][40][41][42][43][44] Translocation events involving 1p have been reported to occur with a wide variety of chromosome ends. Some cytogenetic rearrangements have been reported more than others and a better understanding of these particular rearrangements could provide insights into the formation and stabilization of cytogenetically defined terminal deletions of chromosome 1p through telomere capture.…”

Section: Discussionmentioning

confidence: 99%

FISHing for mechanisms of cytogenetically defined terminal deletions using chromosome-specific subtelomeric probes

2000

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Cytogenetically defined terminal deletions are thought to be a major, yet underappreciated, cause of mental retardation and multiple congenital anomalies. The mechanisms by which terminal deletions arise and are stabilized are not completely understood; although all ends of human chromosomes must have a telomeric cap to be stable. At least three mechanisms exist to maintain chromosome ends with cytogenetically defined terminal deletions: stabilization of terminal deletions through a process of telomere regeneration (termed 'telomere healing'), retention of the original telomere producing interstitial deletions, and formation of derivative chromosomes by obtaining a different telomeric sequence through cytogenetic rearrangement (termed 'telomere capture'). We used chromosome-specific subtelomeric probes and FISH to characterize cytogenetically defined terminal deletions in patients with 1p36 monosomy. Based on the current resolution of these subtelomeric probes, our results indicate that cytogenetically defined terminal deletions of 1p36 are likely to occur through all three mechanisms, although we speculate that the majority of cases were stabilized through telomere regeneration. These results demonstrate the use of chromosome-specific subtelomeric probes as an efficient first step toward uncovering the mechanisms that result in the stabilization of cytogenetically defined terminal deletions.

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Section: Discussionmentioning

confidence: 99%

FISHing for mechanisms of cytogenetically defined terminal deletions using chromosome-specific subtelomeric probes

2000

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“…4,[13][14][15] There is also a number of cases which have a phenotype suggestive of a genetic abnormality, but which do not fit any known syndrome. The 24-colour karyotyping techniques M-FISH and SKY provide one approach to whole genome screening for chromosome abnormalities, but are limited in resolution.…”

Section: Discussionmentioning

confidence: 99%

Identification of a subtle t(16;19)(p13.3;p13.3) in an infant with multiple congenital abnormalities using a 12-colour multiplex FISH telomere assay, M-TEL

et al. 2000

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There is increasing evidence that cytogenetically invisible chromosome rearrangements are an important cause of genetic disease. Clues to the chromosomal location of these rearrangements may be provided by a specific clinical diagnosis, which can then be investigated by targeted FISH or molecular studies. However, the phenotypic features of some microdeletion syndromes are difficult to recognise, particularly in infants. In addition, the presence of other chromosome aneuploidy may mask the typical clinical features. In the present study, the presence of tubers on cranial magnetic resonance imaging (

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“…6 By using this method, several investigations revealed submicroscopic chromosomal deletions and rearrangements in subjects who have an apparently normal karyotype and thus provide evidence that such anomalies are an important unrecognised cause of mental retardation. 7,8 As an alternative to whole genome screening for submicroscopic anomalies, two methods for detecting telomeric rearrangements have been developed and applied to investigate such anomalies in patients with idiopathic mental retardation. The first method relies on detecting deviation from Mendelian inheritance of alleles at polymorphic loci close to telomeres.…”

Section: Introductionmentioning

confidence: 99%

Screening for subtelomeric chromosome abnormalities in children with idiopathic mental retardation using multiprobe telomeric FISH and the new MAPH telomeric assay

et al. 2001

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Subtelomeric chromosomal abnormalities are emerging as an important cause of human genetic disorders. The scope of this investigation was to screen a selected group of children with idiopathic mental retardation for subtelomeric anomalies using the multiprobe telomeric FISH method and also to develop and test a new assay, the MAPH telomeric assay, in the same group of patients. The new MAPH telomeric assay uses the recently published MAPH methodology that permits the measurement of locus copy number by hybridisation with a specifically designed set of probes located at the end of human chromosomes. Seventy patients with idiopathic mental retardation have been screened using the established multiprobe telomeric FISH assay and the new MAPH telomeric assay, for all telomeres. One patient with de novo 8p subtelomeric deletion was identified. The new MAPH telomeric assay confirmed the same results in both normal and abnormal samples. This is the first description of the use of MAPH methodology to detect chromosomal imbalances near the telomeres in idiopathic mentally retarded patients. The new MAPH telomeric assay offers a new, fast, accurate and cost effective diagnostic tool to detect chromosomal imbalances near telomeres in mentally retarded patients, as well as the characterisation of known chromosomal abnormalities, spontaneous recurrent miscarriages, infertility, hematological malignancies, preimplantation genetic diagnosis, and other fields of clinical and research interests.

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Detection of Breakpoints in Submicroscopic Chromosomal Translocation, Illustrating an Important Mechanism for Genetic Disease

Cited by 71 publications

References 22 publications

FISHing for mechanisms of cytogenetically defined terminal deletions using chromosome-specific subtelomeric probes

FISHing for mechanisms of cytogenetically defined terminal deletions using chromosome-specific subtelomeric probes

Identification of a subtle t(16;19)(p13.3;p13.3) in an infant with multiple congenital abnormalities using a 12-colour multiplex FISH telomere assay, M-TEL

Screening for subtelomeric chromosome abnormalities in children with idiopathic mental retardation using multiprobe telomeric FISH and the new MAPH telomeric assay

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