title: A comparison of different metaphase CGH methods for the detection of cryptic chromosome aberrations of defined size.
abstract: An increasing body of evidence indicates that submicroscopic gene dose alterations may cause mental impairment and malformations. During the last decade, comparative genomic hybridization (CGH) has become a useful tool in the detection and mapping of chromosome aberrations. Modifications of CGH with increased resolution down to 3-5 Mb have been reported and CGH is now offered as a diagnostic procedure in the evaluation of patients with idiopathic mental retardation (MR). In order to increase the resolution, we modified the CGH protocol using freshly prepared high-quality metaphase slides and chemical labeling, and tested the method on a set of patients with well-defined submicroscopic chromosome abnormalities with confirmed size 1.3-20.5 Mb. Subsequently, a completely blinded test was performed to compare the performance of the chemical labeling CGH to the commercially available HR-CGH. Using the two different CGH methods, we were able to detect chromosome imbalances down to 2-3 Mb approximately. The HR-CGH method detected all aberrations >6 Mb and a few smaller, while the modified CGH method was able to detect all but three aberrations >1.8 Mb. The modified CGH method was superior in the detection of terminal imbalances, while the HR-CGH software was more successful in the detection of imbalances located very close to the centromeric regions. In conclusion, the resolution of metaphase CGH may be as high as 2-3 Mb but is most likely depending on the chromosomal region involved, a clear limitation when used as a screening method for chromosome aberrations in patients with idiopathic MR.
authors.affiliation: Department of Molecular Medicine, Clinical Genetics Unit, Karolinska Institute, CMM L8:02, Stockholm SE-17176, Sweden. jacqueline.schoumans@cmm.ki.se
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Schoumans
authors.forename: Kate
authors.initials: K
authors.lastname: Nielsen
authors.forename: Iben
authors.initials: I
authors.lastname: Jeppesen
authors.forename: Britt-Marie
authors.initials: BM
authors.lastname: Anderlid
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Blennow
authors.forename: Karen
authors.initials: K
authors.lastname: Brøndum-Nielsen
authors.forename: Magnus
authors.initials: M
authors.lastname: Nordenskjöld
mesh_terms: D002869:Chromosome Aberrations; D025063:Chromosome Disorders / Q000175:diagnosis* / Q000235:genetics; D002874:Chromosome Mapping; D005819:Genetic Markers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008677:Metaphase; D009693:Nucleic Acid Hybridization / Q000379:methods*; D013577:Syndrome
chemical_list: D005819:Genetic Markers