A LINE ELEMENT IS PRESENT AT THE SITE OF A 300-KB DELETION STARTING IN INTRON-10 OF THE PAX6 GENE IN A CASE OF FAMILIAL ANIRIDIA

We have identified a 300-kb germline deletion in 11p13 in a family wit h aniridia but no Wilms' tumor. Cloning and sequencing of the breakpoi nt revealed that the deletion starts in intron 10 of the PAX6 gene and removes the C-terminal part of the proline-serine-threonine rich doma in, leaving both DNA-binding domains intact. The PAX6 gene is joined h ead-to-head to a LINE-1 (L1) element. The L1 is truncated at the 3' en d, removing part of ORF2. Sequencing of the L1 element shows that it d oes not encode a functional transposase and is therefore probably not an active element. These data suggest that the L1 element is normally present at the site of the distal deletion endpoint in 11p13. No exten sive sequence homologies are detected at the deletion junction points; however, the PAX6;gene as well as the L1 element have runs of T nucle otides at this position, indicating that the deletion occurred by nonh omologous recombination. Several consensus recognition sequences for t opoisomerase I flank the deletion site in both sequences, suggesting a n involvement of this enzyme during the deletion-recombination process .