Project: Research project

Project Details


The long term goal of this program is to understand the molecular
basis of velo-cardio-facial syndrome (VCFS) and DiGeorge
syndrome (DGS). The main clinical features of VCFS include
congenial heart defects, craniofacial anomalies and learning
disabilities. The clinical features of DGS include the anomalies of
VCFS and in addition, includes thymus aplasia and
hypoparathyroidism. Because VCFS and DGS share phenotypic
features and are also both associated with overlapping
chromosomal deletions with 22q11, they may share the same
etiology. The precise molecular basis for VCFS and DGS is not
understood. We hypothesize that haploinsufficiency-of a single
gene within 22q11 is responsible for the etiology of the
developmental anomalies of VCFS/DGS. Some of the other
clinical features, not directly attributed to a developmental defect,
may be due to haploinsufficiency of other genes within 2q11. The
goal of this project is to define the deletions that occur in
VCFS/DGS. Towards this goal, we have constructed a physical
map of the 22q11 region. We have found that a common
proximal and distal chromosomal breakpoint occurs in VCFS
patients. As part of this project, we will clone the breakpoint
junction to understand the mechanism for the deletion.
Deletions/translocations that occur in VCGS/DGS patients have
been used to define a critical region of 500 kb. Based upon
current estimates of gene density, 15 genes may be present within
this 500 kb critical region. We have performed hybridization
selection to isolate genes within the critical region. We and others
have isolated 8 genes within this region, and several of these are
novel. Our strategy centers around using our patients to further
narrow the critical region. We will isolate the full length cDHAs
corresponding to the gene(s) that are expressed during
development, as established in Project 2.
Effective start/end date10/1/9611/30/00


  • Genetics