Diagnosis of Genome Pathology in Children with Mental Retardation and Autism by SNP-Oligonucleotide Molecular Karyotyping

Since mental retardation and autism are the commonest brain disorders in children, uncovering their genetic basis is an actual direction in current biomedicine. Application of whole genome scan for studying unbalanced DNA copy number variations allows not only the detection of chromosomal and genomic rearrangements leading to these diseases, but also offer an opportunity to describe pathogenic processes resulting in abnormal functioning of the central nervous system. To assess SNP-oligonucleotide molecular karyotyping (molecular cytogenetic method having the highest resolution for detection of such genomic variations) in diagnostic context, we have analyzed the genome of 100 children suffering from mental retardation and/or autism. Eight numerical and structural chromosome abnormalities (size: >5 Mb) and 20 submicroscopic genomic rearrangements (size: 0.5-3 Mb) were detected. Nine cases exhibited gene mutations manifesting as exonic deletions and duplications associated with the phenotype. As a result, it was concluded that this molecular cytogenetic technique has diagnostic yield no less than 37%. Additionally, further analysis by an original bioinformatics technologies allowed uncovering pathogenic processes associated with the aforementioned mental disturbances in another 55 cases. Thus, combination of SNP-oligonucleotide molecular karyotyping and bioinformatics analysis has high efficiency for detection of genomic pathology and identification of molecular mechanisms for mental retardation and autism.

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