Candidate gene isolation and comparative analysis of a commonly deleted segment of 7q22 implicated in myeloid malignancies

Monosomy 7 and deletion of 7q are recurring abnormalities in malignant myel oid diseases. Here we extensively characterize an similar to 2-Mb commonly deleted segment (CDS) of 7q22 bounded by D7S1503 and D7S1841. Approximately 1.8 Mb of sequence have been generated from this interval, facilitating th e construction of a transcript map that includes large numbers of genes and ESTs. The intron/exon organization of seven genes and expression patterns of three genes were determined, and leukemia samples were screened for muta tions in five genes. We have used polymorphic markers from this region to e xamine leukemia cells for allelic loss within 7q22. Finally, we isolated mo use genomic clones orthologous to several of the characterized human genes. Fluorescence in situ hybridization studies using these clones indicate tha t a region of orthologous synteny lies on proximal mouse chromosome 5. Thes e resources should greatly accelerate the pace of candidate gene discovery in this region.