The 22q11.2 deletion syndrome, which includes DiGeorge and velocardiofacial 
syndromes (DGS/VCFS), is the most common microdeletion syndrome. The majority of 
deleted patients share a common 3 Mb hemizygous deletion of 22q11.2. The 
remaining patients include those who have smaller deletions that are nested 
within the 3 Mb typically deleted region (TDR) and a few with rare deletions 
that have no overlap with the TDR. The identification of chromosome 22-specific 
duplicated sequences or low copy repeats (LCRs) near the end-points of the 3 Mb 
TDR has led to the hypothesis that they mediate deletions of 22q11.2. The entire 
3 Mb TDR has been sequenced, permitting detailed investigation of the LCRs and 
their involvement in the 22q11.2 deletions. Sequence analysis has identified 
four LCRs within the 3 Mb TDR. Although the LCRs differ in content and 
organization of shared modules, those modules that are common between them share 
97-98% sequence identity with one another. By fluorescence in situ hybridization 
(FISH) analysis, the end-points of four variant 22q11.2 deletions appear to 
localize to the LCRs. Pulsed-field gel electrophoresis and Southern 
hybridization have been used to identify rearranged junction fragments from 
three variant deletions. Analysis of junction fragments by PCR and sequencing of 
the PCR products implicate the LCRs directly in the formation of 22q11.2 
deletions. The evolutionary origin of the duplications on chromosome 22 has been 
assessed by FISH analysis of non-human primates. Multiple signals in Old World 
monkeys suggest that the duplication events may have occurred at least 20-25 
million years ago.