Center for Causal Transcriptional Consequences of Human Genetic Variation (CTCHGV)

An NHGRI Center for Excellence in Genomic Science





Principal investigator

Professor George M. Church

Harvard Medical School




Dr. George Q. Daley

Childrens Hospital


Dr. J. Keith Joung

Massachusetts General Hospital


Professor Kun Zhang

University of California at San Diego


Information about CTCHGV


         Goal of our Center

         Our four Specific Aims

         Text of our grant proposal

         Our investigators

         Our commitment to diversity

         Our history

         Contact for further information


         Internal documents (requires password)


X-ray structure of the RecA protein complexed with two partially duplexed single stranded DNAs (ssDNAs) from Chen Nature 453:489 (PubMed, RSCB). RecA plays a key role in homologous recombination (HR) by enabling ssDNA templates to be paired against complementary sequences in genomic DNA during DNA repair. CTCHGV proposes to make extensive use of HR to alter sites of natural human variation near genes in order to identify variations that cause changes in gene expression levels. The starred symbol in the image above is intended to represent a possibly altered base in a template ssDNA strand that we might be aiming to incorporate into a genome by induction of HR through creation of a double stranded break, possibly through expression of a Zinc Finger Nuclease designed to cut near the site to be altered. CTCHGV will also explore other means of altering genomic DNA in human cells, including development of a version of Multiplex Automated Genome Engineering (MAGE) in human cells. In MAGE, short ssDNA oligonucleotides harboring variations relative to the genome are incorporated by a RecA-independent mechanism without the requirement for inducing double-stranded breaks.




Last modified: 10/18/2010 7:33 AM by John Aach