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 Co-investigators 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 et.al. 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