title: Detection of ≥1Mb microdeletions and microduplications in a single cell using custom oligonucleotide arrays.
abstract: OBJECTIVE
  High resolution detection of genomic copy number abnormalities in a single cell is relevant to preimplantation genetic diagnosis and potentially to noninvasive prenatal diagnosis. Our objective is to develop a reliable array comparative genomic hybridization (CGH) platform to detect genomic imbalances as small as ~1Mb ina single cell.
  
  
  METHODS
  We empirically optimized the conditions for oligonucleotide-based array CGH using single cells from multiple lymphoblastoid cell lines with known copy number abnormalities. To improve resolution, we designed custom arrays with high density probes covering clinically relevant genomic regions.
  
  
  RESULTS
  The detection of megabase-sized copy number variations (CNVs) in a single cell was influenced by the number of probes clustered in the interrogated region. Using our custom array, we reproducibly detected multiple chromosome abnormalities including trisomy 21, a 1.2Mb Williams syndrome deletion, and a 1.3Mb CMT1A duplication. Replicate analyses yielded consistent results.
  
  
  CONCLUSIONS
  Aneuploidy and genomic imbalances with CNVs as small as 1.2Mb in a single cell are detectable by array CGH using arrays with high-density coverage in the targeted regions. This approach has the potential to be applied for preimplantation genetic diagnosis to detect aneuploidy and common microdeletion/duplication syndromes and for noninvasive prenatal diagnosis if single fetal cells can be isolated.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Weimin
authors.initials: W
authors.lastname: Bi
authors.forename: Amy
authors.initials: A
authors.lastname: Breman
authors.forename: Chad A
authors.initials: CA
authors.lastname: Shaw
authors.forename: Pawel
authors.initials: P
authors.lastname: Stankiewicz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Gambin
authors.forename: Xinyan
authors.initials: X
authors.lastname: Lu
authors.forename: Sau Wai
authors.initials: SW
authors.lastname: Cheung
authors.forename: Laird G
authors.initials: LG
authors.lastname: Jackson
authors.forename: James R
authors.initials: JR
authors.lastname: Lupski
authors.forename: Ignatia B
authors.initials: IB
authors.lastname: Van den Veyver
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
mesh_terms: D000782:Aneuploidy; D002460:Cell Line; D002607:Charcot-Marie-Tooth Disease / Q000175:diagnosis / Q000235:genetics; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004314:Down Syndrome / Q000175:diagnosis / Q000235:genetics; D018628:Gene Dosage; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D015345:Oligonucleotide Probes; D019836:Preimplantation Diagnosis / Q000379:methods*; D059010:Single-Cell Analysis / Q000379:methods*; D018980:Williams Syndrome / Q000175:diagnosis / Q000235:genetics
chemical_list: D015345:Oligonucleotide Probes