CLONING A BALANCED TRANSLOCATION ASSOCIATED WITH DIGEORGE-SYNDROME AND IDENTIFICATION OF A DISRUPTED CANDIDATE GENE

DiGeorge syndrome (DGS), a developmental defect, is characterized by c ardiac defects and aplasia or hypoplasia of the thymus and parathyroid glands. DGS has been associated with visible chromosomal abnormalitie s and microdeletions of 22q11, but only one balanced translocation - A DU/VDU t(2;22)(q14;q11.21). We now report the cloning of this transloc ation, the identification of a gene disrupted by the rearrangement and the analysis of other transcripts in its vicinity. Transcripts were i dentified by direct screening of cDNA libraries, exon amplification, c DNA selection and genomic sequence analysis using GRAIL. Disruption of a gene in 22q11.2 by the breakpoint and haploinsufficiency of this lo cus in deleted DGS patients make it a strong candidate for the major f eatures associated with this disorder.