The Bonn MR Centre

Coordinator:		Dr. Hartmut Engels
Institution:		Institut für Humangenetik, Universitätsklinikum Bonn
Homepage:		humangenetics.uni-bonn.de/

Intellectual disability or mental retardation (MR) affects approximately 2% of the population. In about half of the patients, no explanation for the MR can be found. New, genome-wide analyses determined that certain very small chromosome aberrations are causal in at least 15% of the patients. These are losses (”deletions”) or gains (“duplications”) of chromosome segments which are too small to be detected by conventional microscopic techniques such as chromosome banding and thus are called “submicroscopic” copy number changes or CNC.
The Bonn MR Centre has been systematically investigating submicroscopic CNCs since 1999. Originally, the clinically well-characterised patients of the investigation sample have been analysed only regarding CNCs near the chromosome ends. Due to methodological advances, genome-wide analyses became possible, using the so-called array-CGH or - in Bonn since 2007- SNP arrays.
The goal of subproject 5 of the MRNET (The Bonn MR Centre) is the identification of candidate genes for mental retardation by the detection and analysis of submicroscopic CNCs. The sample consists of 230 clinically well-characterised patients with MR of unknown cause (February 2009) and is being increased as a part of MRNET efforts. Most patients have additional congenital anomalies such as dysmorphisms or malformations.
In at least 160 of these patients, CNC will be analysed using genome-wide SNP arrays (Illumina Inc., in collaboration with the Department of Genomics; Life & Brain Center; University of Bonn). Due to the high resolution of the arrays and the high frequency of benign copy number variants in all humans, only a small portion of the detected CNCs will be disease-causing. In order to identify these, several analyses are performed: Database investigations determine whether a CNC contains known genes or if it has been described in healthy control persons. Gene-containing, non-variant CNCs above a certain genomic size are then verified using independent techniques and tested for familial occurrence. Inheritance from a healthy parent often indicates that a CNC is a benign variant. Within de novo CNCs (i.e. those that have arisen newly in the patient) candidate genes are identified e.g. by their function and then investigated further. Information about CNCs and the corresponding clinical appearances are being exchanged between the MRNET subprojects in order to facilitate the investigation of promising CNCs.



Additional relevant Internet link:
German Mental Retardation Network