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

An NHGRI Center for Excellence in Genomic Science

 

3CMT_chgbase.2x.gif

 

 

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