Velo-cardio-facial syndrome (VCFS) and DiGeorge syndrome (DGS) are the result of deletions of human chromosome 22qll. More than 90% of the patients have a 3 Mb deletion. All of the genes in the 3 Mb region are present in a single copy in VCFS/DGS patients. It is also likely that in some patients the deletion leads to null mutations in a number of genes by uncovering recessive mutations. The goal of this project is to understand the cellular, developmental and molecular basis for the phenotypes observed in VCFS/DGS patients. Since the major phenotypes associated with VCFS/DGS are the result of developmental abnormalities, we feel that the mouse provides an appropriate model to examine these features. The proposed program has three major set of goals. During the past two years we have shown that the region of 1HSA22q11 is distributed on three different mouse chromosomes: 6, 10 and 16. We characterized a part of MMY16 that corresponds to a part of HSA22q11. We now propose a detailed characterization of portions of MMU 6, 10 and 16 that correspond to HSA22q11 by constructing high resolution bacterial artificial chromosome (BAC) based maps of these regions. We will study the regions of evolutionary breakpoints to assess if those regions are the same as the ones involved in VCFS/DGS breaks. We will generate two different lines of mice, one carrying a mutation in the Ufd11 gene and the second with a mutation in the Tbx1 gene, two candidates for VCFS/DGS associated phenotypes. We will also generate mice carrying deletions in MMU16 and, if necessary, in other parts of the mouse genome. All of the knock-out and deletion bearing mice will be examined for phenotypes associated with VCFS/DGS. We will also examine the role of genetic background in the manifestation of VCFS/DGS phenotype by crossing our knock-out and deletion mice with different mouse strains.
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| DeRosse, Pamela; Funke, Birgit; Burdick, Katherine E et al. (2006) COMT genotype and manic symptoms in schizophrenia. Schizophr Res 87:28-31 |
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| Burdick, Katherine E; Lencz, Todd; Funke, Birgit et al. (2006) Genetic variation in DTNBP1 influences general cognitive ability. Hum Mol Genet 15:1563-8 |
| Long, Jeffrey M; LaPorte, Patricia; Merscher, Sandra et al. (2006) Behavior of mice with mutations in the conserved region deleted in velocardiofacial/DiGeorge syndrome. Neurogenetics 7:247-57 |
| DeRosse, Pamela; Funke, Birgit; Burdick, Katherine E et al. (2006) Dysbindin genotype and negative symptoms in schizophrenia. Am J Psychiatry 163:532-4 |
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