Searching for New Genetic Risk Factors for Neuropsychiatric Disorders in Expression Databases

Genetic variations might contribute to differences in protein activities and gene expression levels observed in complex genetic traits, like neuropsychiatric disease. This finding motivated the development of original approaches using expression studies to guide the finding of new genetic variations. We extended this approach to new genes selected from microarrays studies of brain samples of patients with Alzheimer's disease, major depressive disorder, bipolar affective disorder, and sporadic Creutzfeldt-Jakob disease. The CLCbio Workbench CombinedA (R) version 3.6.2 was initially used to build expression sites tags (ESTs) and mRNA files retrieved, respectively, from the Goldenpath (UCSC) and NCBI databases and latter to perform multiple batches of Smith-Waterman alignments. The total of 438 ESTs sequences were selected after proper stringent parameters were applied to the first set of mismatches. The annotation revealed various classes of variations, most of them deletions ranging from 1 to 10 pb. These deletions were present in coding regions, 5' and 3' UTR regions. Deletions are often associated to major genetic syndromes with dysmorphic features; however, recent studies show that common microdeletions might be highly associated with common neuropsychiatric disorders.