Nesubalansuotų chromosominių struktūros pokyčių paplitimas žmogaus genome ir jų reikšmė intelektinės negalios etiopatogenezei

Intellectual disability (ID) is one of the main disabling conditions in present day environment, and is thought to affect 1 – 3% of the population. It is a highly heterogeneous disorder, with the majority of cases having genetic etiology. The possibilities of specific diagnosis, prevention and treatment are dependent on the search of genes associated with ID. For a long period it has been difficult to elucidate the eatiology of ID. The most efforts at disease-gene identification involved linkage analysis and positional cloning within large families with a large number of affected individuals. The research was limited by factors such as the availability of only a small number of cases/families, locus heterogeneity, or substantially reduced reproductive fitness. The introduction of genomic microarray technology (arrayCGH) to the study of ID has dramatically increased both the identification of novel cytogenetic causes and the biological understanding of the aetiopathogenesis of ID and revealed novel candidate genes for ID. In this study, patients with ID and apparently healthy control population were genotyped with a high-resolution array CGH. Use of array technology has resulted in the discovery of widespread CNVs in the human genome, both polymorphic variation in healthy individuals and novel pathogenic copy number imbalances. The deep bioinformatic analysis of rare, probably pathogenic CNVs has revealed the role of CNVs in the aetiopathogenesis of the central nervous system and identified strong candidate genes in ID and/or other clinical features. The information about common and rare CNVs will be helpful in the clinical interpretation of nonreccurent probably pathogenic CNVs