Down syndrome (DS) is a major cause of mental retardation and congenital heart disease (CHD). Little is known about the molecular events that cause the DS phenotype. The ultimate goal of the proposed research in the program is to define the genes and their functions responsible for the phenotypic features of DS. As a first step, the specific aims of the Clinical Molecular Core are designed to molecularly define the chromosomal regions deleted or duplicated in patients with partial aneuploidy 21 and specific phenotypic features. Three panels including more than 100 cell lines have been assembled. New cases are added at a rate of 10 per year. Each panel now includes a series of overlapping duplications or deletions that span the length of chromosome 21. This panel includes 53 individuals with partial trisomy 21 or partial monosomy 21. The analysis of this panel will combine definition of phenotype with high resolution cytogenetics, fluorescence in situ hybridization, and quantitative Southern blot dosage analysis.
The specific aim i s delineation of a DS (trisomy 21) phenotypic map. Molecular definition of the duplicated regions and the breakpoints will be determined by quantitative Southern blot analysis suing chromosome 21 unique DNA sequences. Phenotypic features will be established according to the NICHD DS conference (4/90). The panel is informative for holoprosencephaly, mental retardation, skeletal dysplasia, immune deficits, DS CHD, duodenal stenosis, and leukemia in addition to the physical, radiological, cognitive, neurologic and laboratory features of DS. A database will be used to record clinical, cytogenetic and molecular data. Chromosomal constitution will be determined using high resolution cytogenetic analysis and in situ hybridization. The core will provide a basic resource of partially aneuploid individuals and their cell lines with which to study the expression of chromosome 21 and the role of specific genes in determining organismal phenotype.
| Régnier, Vinciane; Billard, Jean-Marie; Gupta, Sapna et al. (2012) Brain phenotype of transgenic mice overexpressing cystathionine ?-synthase. PLoS One 7:e29056 |
| Moat, Stuart; Carling, Rachel; Nix, Authur et al. (2010) Multicentre age-related reference intervals for cerebrospinal fluid serine concentrations: implications for the diagnosis and follow-up of serine biosynthesis disorders. Mol Genet Metab 101:149-52 |
| Nielsen, Darci M; Evans, Jeffrey J; Derber, William J et al. (2009) Mouse model of fragile X syndrome: behavioral and hormonal response to stressors. Behav Neurosci 123:677-86 |
| Knox, Aaron J; Graham, Christine; Bleskan, John et al. (2009) Mutations in the Chinese hamster ovary cell GART gene of de novo purine synthesis. Gene 429:23-30 |
| Hoger, Joachim; Patterson, David; Hoger, Harald et al. (2009) Mice transgenic for reduced folate carrier: an animal model of Down syndrome? Amino Acids 36:349-57 |
| Patterson, David; Graham, Christine; Cherian, Christina et al. (2008) A humanized mouse model for the reduced folate carrier. Mol Genet Metab 93:95-103 |
| Pennington, Bruce F (2006) From single to multiple deficit models of developmental disorders. Cognition 101:385-413 |
| Yao, Guimei; Chen, Xiao-Ning; Flores-Sarnat, Laura et al. (2006) Deletion of chromosome 21 disturbs human brain morphogenesis. Genet Med 8:1-7 |
| Wenger, Galen R; Schmidt, Cecilia; Davisson, Muriel T (2004) Operant conditioning in the Ts65Dn mouse: learning. Behav Genet 34:105-19 |
| Gardiner, Katheleen; Davisson, Muriel T; Crnic, Linda S (2004) Building protein interaction maps for Down's syndrome. Brief Funct Genomic Proteomic 3:142-56 |
Showing the most recent 10 out of 155 publications
