Project description:Objectives:
1. To examine the variations in clinical features, survival outcomes, family history, and health behavior among proband patients who are known or suspected to have a hereditary colorectal cancer syndrome
2. To compare the clinical features, survival outcomes, and health behavior of the proband vs. his/her family members who may or may not be affected by the hereditary colorectal cancer syndrome
3. To explore for correlations between germline genetic variations in both the probands and family members with observed variations in the overall disease phenotype across probands and kindreds, within a given syndrome. Disease phenotype is defined to include: (1) clinicopathologic features including patient demographics and oncologic outcomes; (2) clinical manifestations of disease including the timing, spectrum and severity of CRC and extracolonic cancers. Genetic variations may include the specific codon mutated, the type of mutation and sequence alteration (e.g. nonsense, missense etc), chromosomal/gene copy number changes, and gene polymorphisms.
4. To explore for correlations between germline genetic variations in both the probands and family members with observed variations in somatic CRC tumor biology, including tumor pathology and other tumor molecular markers
Project description:Intellectual disability is a common condition that carries lifelong severe medical and developmental consequences. The causes of intellectual disability (ID) remain unknown for the majority of patients due to the extensive clinical and genetic heterogeneity of this disorder. De novo mutations may play an important role in ID as most individuals with ID present as isolated cases without family history and/or clear syndromic indication. In addition, the involvement of such mutations have recently been demonstrated in a small number of individuals with ID. Here we evaluate the diagnostic potential and role of de novo mutations in a cohort of 100 patients with ID of unknown cause using family-based exome sequencing. Single end short-read (50 bp) SOLiD 4 sequencing data for 300 individuals, constituting 100 patient-parent trios. For more details please read; http://www.nejm.org/doi/full/10.1056/NEJMoa1206524. Dataset is created by RUNMC (Radboud University, Nijmegen Medical Center), partner of Geuvadis consortium (http://www.geuvadis.org).
Project description:To assess variation and inheritance of genome-wide patterns of DNA methylation simultaneously in humans, we applied reduced representation bisulfite sequencing (RRBS) to somatic DNA from six members of a three-generation family. Reduced representation bisulfite sequencing was applied to genomic DNA from leukocytes of 6 family members and two unrelated individuals.
Project description:To evaluate the effect on lincRNA expression by p53 family members, we overexpressed p53 family members in H1299 cells and evaluated the lincRNA expression by microarray analysis.
Project description:Using ChIP-chip assays, we examined the binding patterns of three members of E2F family in five different cell types. Keywords: ChIP-chip
Project description:Members of the GATA protein family play important roles in lineage specification and transdifferentiation. Previous reports show that some members of GATA protein family also can induce pluripotency in somatic cells by substituting for the key pluripotency-associated factor Oct4. However, the mechanism that links the lineage specifying cues and activation of pluripotency remains elusive. Here, we report that all GATA family members can substitute for Oct4 to induce pluripotency. We found that all members of the GATA family can inhibit elevated ectodermal-lineage genes, which is consistent with previous reports that a balance of different lineage-specifying forces is important for restoration of pluripotency. A conserved DNA-binding domain in the C-terminal zinc finger is critical for the GATA family to induce pluripotency. Using RNA-seq and ChIP-seq we identified that the pluripotency-related gene Sall4 is a direct target of GATA family members during reprogramming, serving as a bridge linking the lineage-specific GATA family to the pluripotency circuit. Thus, the GATA family is the first family of proteins wherein all members can function as inducers of the reprogramming process that can substitute for Oct4. Our results suggest that the roles of the GATA family in reprogramming have been greatly underestimated, and that the GATA family may serve as a general mediator for cell fate conversion.