title: Custom oligonucleotide array-based CGH: a reliable diagnostic tool for detection of exonic copy-number changes in multiple targeted genes.
abstract: The frequency of disease-related large rearrangements (referred to as copy-number mutations, CNMs) varies among genes, and search for these mutations has an important place in diagnostic strategies. In recent years, CGH method using custom-designed high-density oligonucleotide-based arrays allowed the development of a powerful tool for detection of alterations at the level of exons and made it possible to provide flexibility through the possibility of modeling chips. The aim of our study was to test custom-designed oligonucleotide CGH array in a diagnostic laboratory setting that analyses several genes involved in various genetic diseases, and to compare it with conventional strategies. To this end, we designed a 12-plex CGH array (135k; 135 000 probes/subarray) (Roche Nimblegen) with exonic and intronic oligonucleotide probes covering 26 genes routinely analyzed in the laboratory. We tested control samples with known CNMs and patients for whom genetic causes underlying their disorders were unknown. The contribution of this technique is undeniable. Indeed, it appeared reproducible, reliable and sensitive enough to detect heterozygous single-exon deletions or duplications, complex rearrangements and somatic mosaicism. In addition, it improves reliability of CNM detection and allows determination of boundaries precisely enough to direct targeted sequencing of breakpoints. All of these points, associated with the possibility of a simultaneous analysis of several genes and scalability 'homemade' make it a valuable tool as a new diagnostic approach of CNMs.
authors: Assistance Publique-Hôpitaux de Paris, Laboratoire de Biochimie et Génétique Moléculaire, Hôpital Cochin, APHP, Paris, France.
authors: Aurélie
authors: A
authors: Vasson
authors: Céline
authors: C
authors: Leroux
authors: Lucie
authors: L
authors: Orhant
authors: Mathieu
authors: M
authors: Boimard
authors: Aurélie
authors: A
authors: Toussaint
authors: Chrystel
authors: C
authors: Leroy
authors: Virginie
authors: V
authors: Commere
authors: Tiffany
authors: T
authors: Ghiotti
authors: Nathalie
authors: N
authors: Deburgrave
authors: Yoann
authors: Y
authors: Saillour
authors: Isabelle
authors: I
authors: Atlan
authors: Corinne
authors: C
authors: Fouveaut
authors: Cherif
authors: C
authors: Beldjord
authors: Sophie
authors: S
authors: Valleix
authors: France
authors: F
authors: Leturcq
authors: Catherine
authors: C
authors: Dodé
authors: Thierry
authors: T
authors: Bienvenu
authors: Jamel
authors: J
authors: Chelly
authors: Mireille
authors: M
authors: Cossée
mesh_terms: D016022:Case-Control Studies; D055028:Comparative Genomic Hybridization / Q000379:methods*; D003550:Cystic Fibrosis / Q000175:diagnosis / Q000235:genetics; D056915:DNA Copy Number Variations; D005091:Exons; D005260:Female; D020440:Gene Duplication; D005817:Genetic Counseling; D005820:Genetic Testing / Q000379:methods; D006467:Hemophilia A / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D017436:Kallmann Syndrome / Q000175:diagnosis / Q000235:genetics; D008297:Male; D015518:Rett Syndrome / Q000175:diagnosis / Q000235:genetics; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion