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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.
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Mimice, Croatia |
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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). |
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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).
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