Laboratory of Maja Bucan

     
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  Dr. Bucan's laboratory is using classical genetic, genomic and bioinformatics approaches to determine genetic determinants of psychiatric and neurological disorders. These studies start with the genetic dissection of a complex psychiatric syndrome into components or endophenotypes, followed by the identification of genes that underlie these traits in an animal model. Over the last 10 years we have performed several forward genetics screens for behavioral and developmental mutants in the mouse. These studies showed that even a small-scale screen, of 500-1000 G1 (dominant screen) or G3 (recessive screen) animals, can identify a large number of mutants. However the usefulness of these mutants depends on the timely positional cloning of the gene causing the mutant phenotype. The goal of the NeuroGenome Project is to use bioinformatics and computational biology approaches to develop databases and tools for the analysis of behavioral mutants in the mouse and selection of candidate genes for these mutants, as well as candidate genes for psychiatric and neurological diseases in humans.
Mimice, Croatia
  ClockDB: (Restricted Access) A novel and promising approach in human genetics is to use a set of pathway-linked genes in association and/or transmission disequilibrium analyses of complex disorders. We hypothesize that combinations of polymorphisms in pathway-linked genes are more likely to reveal complex and possibly epistatic interactions that underlie a polygenic disorder than studies of individual single gene defects. With the assumption that anomalies in circadian behavior represent a valid endophenotype for bipolar disorders, we initiated integration of functional genomics resources and analysis of genetic variation of known core clock genes and genes controlled by the central clock (downstream or output genes) that map to the bipolar candidate regions. (Collaboration with Drs. Wade Berrettini and Chris Stoeckert, Penn).  
  SynapseDB: (Restricted Access) The finding that anomalies in synapse formation and synaptic conductivity may lead to behavioral changes in human disease suggest that a large number of genes involved in synapse formation and function represent valid candidate genes. SynapseDB is a database of components (genes/proteins) that are the functional building blocks of a neuronal synapse. This database contains information on sequence and genetic variation, expression patterns and phenotypes of these genes in the human genome and their orthologs in model organisms. Efforts are underway to identify and compare conserved elements in the upstream and intronic regions of over 150 synaptic genes. Phylogenomic analyses of gene and protein sequences for several large gene families allowed comparison of evolutionary changes in different gene families, identification of "species-specific" paralogs and analysis of evolutionary dynamics of protein-coding and non-coding regions. Finally, analysis of conserved non-coding elements in the context of expression (microarray) data will greatly facilitate the search for functionally important sequences contributing to the regulation of these genes.
(Collaboration with Drs. Junhyong Kim and Lyle Ungar, PCBI, Penn).