The desmocollins and desmogleins are members of the cadherin family of adhesive proteins present in the desmosome type of cell-cell junction. All of the known desmoglein and desmocollin isoforms, which have differing tissue and developmental distributions, are coded by very closely linked genes at 18q12.1. We have previously described YAC clones carrying all three known desmoglein (DSG) genes. We have now isolated YAC clones that carry all three known desmocollin genes (DSC1, 2, and 3) from two libraries and also isolated clones that join the DSC locus to the DSG locus, forming a complete contig for the region. Absence of chimeric ends for some of the YACs was confirmed by isolating Vectorette PCR products for the YAC ends and mapping the derived DNA sequences back to other YACs from CEPH. The whole DSC/DSG gene complex occupies no more than about 700 kb, and the genes are arranged in the order cen-3'-DSC3-DSC2-DSC1-5'-5'-DSG1-DSG3-D SG2-3'-tel, so that the two gene clusters are transcribed outward from the interlocus region. A P1 clone carrying part of DSC2 and DSC3 confirmed the relative orientation of transcription of these two genes. The conservation of close genetic linkage may be of trivial importance related to the recent duplication of these genes or may be because there is a region within the locus that is involved in coordinating the expression of the desmoglein and desmocollin genes.