New approaches are being developed to maximally integrate information from the data generated using omics technologies to uncover pathways involved in disease pathogenesis. In this program project, we will take advantage of state-of-the-art molecular and analytic tools through well-integrated Projects and Cores to better understand how biological processes are defined at the molecular level, how they can be disrupted to cause nonsyndromic coronal craniosynostosis, and how we can assess the risk of and intervene to prevent this birth defect. Molecular/Analytic Core B objective is to generate high quality genomic and imaging data and provide analytic support for all three Projects to allow comprehensive integrative analyses for the Craniosynostosis Network. The Molecular/Analytic Core will fulfill five major tasks: 1) to generate and quality- control high- and medium throughput genetic and genomic data to be used by Projects II and III; 2) to generate analyzable morphometric craniofacial data from pre-operational computer tomography (CT) scans; 3) to integrate clinical information obtained from the participating sites with imaging and genetic/genomic data and organize them so that they meet the needs of different Projects, 4) to provide general and specialized statistical support to Project I and Project II, and 5) to facilitate the selection of the top genetic signals observed across all Projects within the Craniosynostosis Network for the replication study. DNA samples will be processed and analyzed using the Illumina HumanOmniExpressExome high throughput genotyping chip, whole exome sequencing, and medium throughput genotyping for the replication studies in the DNA core at Icahn School of Medicine at Mount Sinai. CT images will be processed to generate craniofacial measurements and craniosynostosis severity scores to be used for association studies and to select most informative individuals for sequencing. Genomic and imaging data will be quality-controlled and linked with the phenotype data obtained from the participating sites. The Molecular/Analytic Core will also facilitate bioinformatics and statistical analyses pertinent to each project, including gene expression analysis, rare variant analysis, genome-wide association studies, pathway-based analysis, and replication studies by generating appropriate dataset formats and disseminating results obtained by each project. In addition, the Molecular/Analytic Core will be responsible for data storage and integration across the Projects and Cores, as well as dataset preparation for future data deposition and sharing.

National Institute of Health (NIH)
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZHD1-DRG-D)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Icahn School of Medicine at Mount Sinai
Domestic Higher Education
New York
United States
Zip Code
Ye, Xiaoqian; Guilmatre, Audrey; Reva, Boris et al. (2016) Mutation Screening of Candidate Genes in Patients with Nonsyndromic Sagittal Craniosynostosis. Plast Reconstr Surg 137:952-61
Singh, Nandini; Dutka, Tara; Reeves, Roger H et al. (2016) Chronic up-regulation of sonic hedgehog has little effect on postnatal craniofacial morphology of euploid and trisomic mice. Dev Dyn 245:114-22
Flaherty, Kevin; Singh, Nandini; Richtsmeier, Joan T (2016) Understanding craniosynostosis as a growth disorder. Wiley Interdiscip Rev Dev Biol 5:429-59
Lee, Chanyoung; Richtsmeier, Joan T; Kraft, Reuben H (2015) A computational analysis of bone formation in the cranial vault in the mouse. Front Bioeng Biotechnol 3:24
Weiss, Ken; Buchanan, Anne; Richtsmeier, Joan (2015) How are we made?: Even well-controlled experiments show the complexity of our traits. Evol Anthropol 24:130-6
Trainor, Paul A; Richtsmeier, Joan T (2015) Facing up to the challenges of advancing Craniofacial Research. Am J Med Genet A 167:1451-4
Singh, Nandini; Dutka, Tara; Devenney, Benjamin M et al. (2015) Acute upregulation of hedgehog signaling in mice causes differential effects on cranial morphology. Dis Model Mech 8:271-9
Richtsmeier, Joan T; Jones, Marilyn C; Lozanoff, Scott et al. (2015) The Society for Craniofacial Genetics and Developmental Biology 37th annual meeting. Am J Med Genet A 167:1455-73
Heuzé, Yann; Holmes, Gregory; Peter, Inga et al. (2014) Closing the Gap: Genetic and Genomic Continuum from Syndromic to Nonsyndromic Craniosynostoses. Curr Genet Med Rep 2:135-145
Lee, Chanyoung; Richtsmeier, Joan T; Kraft, Reuben H (2014) A MULTISCALE COMPUTATIONAL MODEL FOR THE GROWTH OF THE CRANIAL VAULT IN CRANIOSYNOSTOSIS. Int Mech Eng Congress Expo 2014: