title: Single-cell chromosomal imbalances detection by array CGH.
abstract: Genomic imbalances are a major cause of constitutional and acquired disorders. Therefore, aneuploidy screening has become the cornerstone of preimplantation, prenatal and postnatal genetic diagnosis, as well as a routine aspect of the diagnostic workup of many acquired disorders. Recently, array comparative genomic hybridization (array CGH) has been introduced as a rapid and high-resolution method for the detection of both benign and disease-causing genomic copy-number variations. Until now, array CGH has been performed using a significant quantity of DNA derived from a pool of cells. Here, we present an array CGH method that accurately detects chromosomal imbalances from a single lymphoblast, fibroblast and blastomere within a single day. Trisomy 13, 18, 21 and monosomy X, as well as normal ploidy levels of all other chromosomes, were accurately determined from single fibroblasts. Moreover, we showed that a segmental deletion as small as 34 Mb could be detected. Finally, we demonstrated the possibility to detect aneuploidies in single blastomeres derived from preimplantation embryos. This technique offers new possibilities for genetic analysis of single cells in general and opens the route towards aneuploidy screening and detection of unbalanced translocations in preimplantation embryos in particular.
authors.affiliation: Center for Human Genetics, University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Cedric
authors.initials: C
authors.lastname: Le Caignec
authors.forename: Claudia
authors.initials: C
authors.lastname: Spits
authors.forename: Karen
authors.initials: K
authors.lastname: Sermon
authors.forename: Martine
authors.initials: M
authors.lastname: De Rycke
authors.forename: Bernard
authors.initials: B
authors.lastname: Thienpont
authors.forename: Sophie
authors.initials: S
authors.lastname: Debrock
authors.forename: Catherine
authors.initials: C
authors.lastname: Staessen
authors.forename: Yves
authors.initials: Y
authors.lastname: Moreau
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fryns
authors.forename: Andre
authors.initials: A
authors.lastname: Van Steirteghem
authors.forename: Inge
authors.initials: I
authors.lastname: Liebaers
authors.forename: Joris R
authors.initials: JR
authors.lastname: Vermeesch
mesh_terms: D000782:Aneuploidy; D001757:Blastomeres / Q000737:chemistry; D002460:Cell Line; D025063:Chromosome Disorders / Q000175:diagnosis; D004247:DNA / Q000032:analysis; D005347:Fibroblasts / Q000737:chemistry; D005820:Genetic Testing / Q000379:methods*; D004854:Herpesvirus 4, Human; D006801:Humans; D008214:Lymphocytes / Q000737:chemistry / Q000821:virology; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D019836:Preimplantation Diagnosis / Q000379:methods*
chemical_list: D004247:DNA