The Database Core (Core B) has served this Program in the past as a repository for tracking samples (DNA, cell lines, tissue samples etc.) and genetic information including mutation screening results and genotyping data inclusive of CNV data. The database has been expanded to include clinical information on our cohort of over 1200 CdLS probands and family members. This resource has allowed for a nimble approach to genotpye-phenotype studies as well as to identify cohorts for screening of novel candidate genes. With the expansion over the past few years of genome-wide data from Drosophila, zebrafish, mouse and human cell lines a need to establish a secure and easily accessible database that integrates all of these variable genomic datasets woud be invaluable to the next stages of experimentation that is being proposed in the continuation of this Program Project. The goal of the Database and Resource Sharing Core is to improve and maintain the existing genetic and clinical database of CdLS probands and family members and to: a) Expand our knowledge of the extent and type of correlations between structural abnormalities and molecular data by integrating:!) phenotypic data, 2)genotype data generated in Project 1 including: gene mutations and variants, genome-wide SNP, CNV, ChIP, expression and epigenetic imprint data, 3) Mouse and Zebrafish data generated as part of Project 11 including: genome-wide expression data, targeted gene expression data, organ/tissue specific expression data, phenotypic data from knock-out and conditional knock out mouse models as well as from RNAi Zebrafish models and 4) Drosophila data generated as part of Project 111 including: genome-wide tissue-specific expression and ChIP data, functional targeted gene expression data and phenotypic data. b) Provide a communication vehicle for the exchange and management of clinical and molecular data as well as the resources generated in the three component projects of this application. c) Expand a secure web-based access to the clinical and laboratory database, including access to listings of resources to be shared with outside investigators.

Public Health Relevance

The Database Core will evolve into an on-line database that will allow the 3 Project Leaders and their labs to enter, read and analyze information as it is generated at all centers. This will facilitate the discovery process and allow for an enriched integrative dataset that will complement each individual project and allow for timely review of progress. Once built and with the appropriate privacy and subject protection safeguards in place, it is anticipated that this database will be made available as a resource to the research community at large.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
5P01HD052860-07
Application #
8378236
Study Section
Special Emphasis Panel (ZHD1-DSR-N)
Project Start
Project End
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
7
Fiscal Year
2012
Total Cost
$78,677
Indirect Cost
$38,712
Name
Children's Hospital of Philadelphia
Department
Type
DUNS #
073757627
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
Yuen, Kobe C; Xu, Baoshan; Krantz, Ian D et al. (2016) NIPBL Controls RNA Biogenesis to Prevent Activation of the Stress Kinase PKR. Cell Rep 14:93-102
Lopez-Burks, Martha E; Santos, Rosaysela; Kawauchi, Shimako et al. (2016) Genetic enhancement of limb defects in a mouse model of Cornelia de Lange syndrome. Am J Med Genet C Semin Med Genet 172:146-54
Kawauchi, Shimako; Santos, Rosaysela; Muto, Akihiko et al. (2016) Using mouse and zebrafish models to understand the etiology of developmental defects in Cornelia de Lange Syndrome. Am J Med Genet C Semin Med Genet 172:138-45
Santos, Rosaysela; Kawauchi, Shimako; Jacobs, Russell E et al. (2016) Conditional Creation and Rescue of Nipbl-Deficiency in Mice Reveals Multiple Determinants of Risk for Congenital Heart Defects. PLoS Biol 14:e2000197
Dorsett, Dale (2016) The Drosophila melanogaster model for Cornelia de Lange syndrome: Implications for etiology and therapeutics. Am J Med Genet C Semin Med Genet 172:129-37
Wu, Yaning; Gause, Maria; Xu, Dongbin et al. (2015) Drosophila Nipped-B Mutants Model Cornelia de Lange Syndrome in Growth and Behavior. PLoS Genet 11:e1005655
Ramos, Feliciano J; Puisac, Beatriz; Baquero-Montoya, Carolina et al. (2015) Clinical utility gene card for: Cornelia de Lange syndrome. Eur J Hum Genet 23:
Izumi, Kosuke; Nakato, Ryuichiro; Zhang, Zhe et al. (2015) Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin. Nat Genet 47:338-44
Krantz, Ian D (2014) Cohesin embraces new phenotypes. Nat Genet 46:1157-8
Visnes, T; Giordano, F; Kuznetsova, A et al. (2014) Localisation of the SMC loading complex Nipbl/Mau2 during mammalian meiotic prophase I. Chromosoma 123:239-52

Showing the most recent 10 out of 66 publications