How microsatellite analysis can be exploited for subtelomeric chromosomal rearrangement analysis in mental retardation

Borgione, Eugenia; Giudice, Mariangela Lo; Galesi, Ornella; Castiglia, Lucia; Failla, Pinella; Romano, Corrado; Ragusa, Angela; Fichera, Marco

doi:10.1136/jmg.38.1.e1

Cited by 23 publications

(10 citation statements)

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“…The ®rst consideration is labor, and this must include the subsequent studies that are engendered by an abnormal result of the screening. In our study [Rosenberg et al, 2001] of 120 patients using STRP markers, we (like others [Borgione et al, 2001;Colleaux et al, 2001]) argued that STRPs are robust, cheap, and can be automated. In our experience, this turned out to be true only in the narrowest sense.…”

Section: Methodsmentioning

confidence: 91%

“…The reality is that we generated many more false positives than true positives (due to null alleles, allele mutations, and polymorphic telomeres). In order to determine if these results were false positives, we did hundreds of hours of work, ordered numerous new primers, and [Rosenberg et al, 2001] and 0 of 30 cases [Borgione et al, 2001]), but one group has detected an apparent single case among 24 subjects screened ]. This deserves future study.…”

Section: Methodsmentioning

confidence: 99%

“…The results of these studies contribute to a suddenly sizable body of data. Including the three papers in this issue, I have identi®ed 14 studies that include 1,718 subjects [Flint et al, 1995;Vorsanova et al, 1998;Knight et al, 1999;Lamb et al, 1999;Slavotinek et al, 1999;Joly et al, 2001;Borgione et al, 2001;Colleaux et al, 2001;Rossi et al, 2001;Anderlid et al, 2002;Baker et al, 2002;Clarkson et al, 2002;Riegel et al, 2001;Rosenberg et al, 2001]. (Table I).…”

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confidence: 98%

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The end of the beginning of chromosome ends†

Biesecker

2002

Am. J. Med. Genet.

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Section: Methodsmentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

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confidence: 98%

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The end of the beginning of chromosome ends†

Biesecker

2002

Am. J. Med. Genet.

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“…MAPH compares favourably with other techniques used for subtelomeric DNA screening. Inheritance at short tandem repeat polymorphisms (STRPs) has been used to detect copy number changes at subtelomeric regions, [21][22][23] but this technique depends on the informativeness of the STRPs used, needs DNA samples from parents, may miss duplications, and requires multiple PCRs to screen each karyotype. A recent paper applied array comparative genomic hybridisation (array-CGH) to screen for subtelomeric copy number changes.…”

Section: Discussionmentioning

confidence: 99%

High throughput screening of human subtelomeric DNA for copy number changes using multiplex amplifiable probe hybridisation (MAPH)

Hollox

Atia²,

Cross³

et al. 2002

Journal of Medical Genetics

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Background: Subtelomeric regions of the human genome are gene rich, with a high level of sequence polymorphism. A number of clinical conditions, including learning disability, have been attributed to subtelomeric deletions or duplications, but screening for deletion in these regions using conventional cytogenetic methods and fluorescence in situ hybridisation (FISH) is laborious. Here we report that a new method, multiplex amplifiable probe hybridisation (MAPH), can be used to screen for copy number at subtelomeric regions. Methods: We have constructed a set of MAPH probes with each subtelomeric region represented at least once, so that one gel lane can assay copy number at all chromosome ends in one person. Each probe has been sequenced and, where possible, its position relative to the telomere determined by comparison with mapped clones. Results: The sensitivity of the probes has been characterised on a series of cytogenetically verified positive controls and 83 normal controls were used to assess the frequency of polymorphic copy number with no apparent phenotypic effect. We have also used MAPH to test a cohort of 37 people selected from males referred for fragile X syndrome testing and found six changes that were confirmed by dosage PCR. Conclusions: MAPH can be used to screen subtelomeric regions of chromosomes for deletions and duplications before confirmation by FISH or dosage PCR. The high throughput nature of this technique allows it to be used for large scale screening of subtelomeric copy number, before confirmation by FISH. In practice, the availability of a rapid and efficient screen may allow subtelomeric analysis to be applied to a wider selection of patients than is currently possible using FISH alone.

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“…Many studies have used molecular techniques with probes mapping to the subtelomeric regions one by one, in pooled sets, or in microarrays [reviewed in De Vries et al, 2003;Flint and Knight, 2003]. A smaller number of studies used polymorphic markers [Borgione et al, 2001;Colleaux et al, 2001;Flint et al, 1995;Rio et al, 2002;Rosenberg et al, 2001;Slavotinek et al, 1999] or high-resolution comparative genomic hybridization [Harada et al, 2004;Kirchhoff et al, 2004;Ness et al, 2002]. These studies showed that 1-8% of mentally retarded individuals have subtelomeric imbalances of Z150 kb, and therefore represent a hitherto undetected category of mutations.…”

Section: Introductionmentioning

confidence: 98%

Detection of cryptic subtelomeric chromosome abnormalities and identification of anonymous chromatin using a quantitative multiplex ligation-dependent probe amplification (MLPA) assay

et al. 2005

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The need to detect clinically significant segmental aneuploidies beyond the range of light microscopy demands the development of new cost-efficient, sensitive, and robust analytical techniques. Multiplex ligation-dependent probe amplification (MLPA) has already been shown to be particularly effective and flexible for measuring copy numbers in a multiplex format. Previous attempts to develop a reliable MLPA to assay all chromosome subtelomeric regions have been confounded by unforeseen copy number variation in some genes that are very close to the telomeres in healthy individuals. We addressed this shortcoming by substituting all known polymorphic probes and using two complementary multiplex assays to minimize the likelihood of false results. We developed this new quantitative MLPA strategy for two important diagnostic applications. First, in a group of cases with high clinical suspicion of a chromosome abnormality but normal, high-resolution karyotypes, MLPA detected subtelomeric abnormalities in three patients. Two were de novo terminal deletions (del(4p) and del(1p)), and one was a derivative chromosome 1 from a maternal t(1p;17p). The range of these segmental aneuploidies was 1.8-6.6 Mb, and none were visible on retrospective microscopy. Second, in a group of six patients with apparently de novo single-chromosome abnormalities containing anonymous chromatin, MLPA identified two cases with simple intrachromosomal duplications: dup(6p) and dup(8q). Three cases showed derivative chromosomes from translocations involving the distal regions of 9q and 4q, 5p and 11q, and 6q and 3p. One case showed a nonreciprocal, interchromosomal translocation of the distal region of 10p-7p. All abnormalities in both groups were confirmed by fluorescence in situ hybridization (FISH) using bacterial artificial chromosomes (BACs). This quantitative MLPA technique for subtelomeric assays is compared with previously described alternative techniques.

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How microsatellite analysis can be exploited for subtelomeric chromosomal rearrangement analysis in mental retardation

Cited by 23 publications

References 9 publications

The end of the beginning of chromosome ends†

The end of the beginning of chromosome ends†

High throughput screening of human subtelomeric DNA for copy number changes using multiplex amplifiable probe hybridisation (MAPH)

Detection of cryptic subtelomeric chromosome abnormalities and identification of anonymous chromatin using a quantitative multiplex ligation-dependent probe amplification (MLPA) assay

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