Identification of non-recurrent submicroscopic genome imbalances: The advantage of genome-wide microarrays over targeted approaches

David A. Koolen, Erik A. Sistermans, Willy Nilessen, Samantha J L Knight, Regina Regan, Yan T. Liu, R. Frank Kooy, Liesbeth Rooms, Corrado Romano, Marco Fichera, Albert Schinzel, Alessandra Baumer, Britt Marie Anderlid, Jacqueline Schoumans, Ad Geurts van Kessel, Magnus Nordenskjold, Bert B A de Vries

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)395-400
Number of pages6
JournalEuropean Journal of Human Genetics
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 2008

ASJC Scopus subject areas

  • Genetics(clinical)

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