title: Identification of non-recurrent submicroscopic genome imbalances: the advantage of genome-wide microarrays over targeted approaches.
abstract: Genome-wide analysis of DNA copy-number changes using microarray-based technologies has enabled the detection of de novo cryptic chromosome imbalances in approximately 10% of individuals with mental retardation. So far, the majority of these submicroscopic microdeletions/duplications appear to be unique, hampering clinical interpretation and genetic counselling. We hypothesised that the genomic regions involved in these de novo submicroscopic aberrations would be candidates for recurrent copy-number changes in individuals with mental retardation. To test this hypothesis, we used multiplex ligation-dependent probe amplification (MLPA) to screen for copy number changes at eight genomic candidate regions in a European cohort of 710 individuals with idiopathic mental retardation. By doing so, we failed to detect additional submicroscopic rearrangements, indicating that the anomalies tested are non-recurrent in this cohort of patients. The break points flanking the candidate regions did not contain low copy repeats and/or sequence similarities, thus providing an explanation for its non-recurrent nature. On the basis of these data, we propose that the use of genome-wide microarrays is indicated when testing for copy-number changes in individuals with idiopathic mental retardation.
authors.affiliation: Department of Human Genetics, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: David A
authors.initials: DA
authors.lastname: Koolen
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
authors.forename: Willy
authors.initials: W
authors.lastname: Nilessen
authors.forename: Samantha J L
authors.initials: SJ
authors.lastname: Knight
authors.forename: Regina
authors.initials: R
authors.lastname: Regan
authors.forename: Yan T
authors.initials: YT
authors.lastname: Liu
authors.forename: R Frank
authors.initials: RF
authors.lastname: Kooy
authors.forename: Liesbeth
authors.initials: L
authors.lastname: Rooms
authors.forename: Corrado
authors.initials: C
authors.lastname: Romano
authors.forename: Marco
authors.initials: M
authors.lastname: Fichera
authors.forename: Albert
authors.initials: A
authors.lastname: Schinzel
authors.forename: Alessandra
authors.initials: A
authors.lastname: Baumer
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Anderlid
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schoumans
authors.forename: Ad Geurts
authors.initials: AG
authors.lastname: van Kessel
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjold
authors.forename: Bert B A
authors.initials: BB
authors.lastname: de Vries
mesh_terms: D001483:Base Sequence; D002874:Chromosome Mapping; D015331:Cohort Studies; D017931:DNA Primers; D015894:Genome, Human; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D022521:Ligase Chain Reaction; D020411:Oligonucleotide Array Sequence Analysis
chemical_list: D017931:DNA Primers