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

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