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 with aniridia but no Wilms' tumor. Cloning and sequencing of the breakpoint revealed that the deletion starts in intron 10 of the PAX6 gene and removes the C-terminal part of the proline-serine-threonine rich domain, leaving both DNA-binding domains intact. The PAX6 gene is joined head-to-head to a LINE-1 (L1) element. The L1 is truncated at the 3' end, removing part of ORF2. Sequencing of the L1 element shows that it does 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 extensive sequence homologies are detected at the deletion junction points; however, the PAX6 gene as well as the L1 element have runs of T nucleotides at this position, indicating that the deletion occurred by nonhomologous recombination. Several consensus recognition sequences for topoisomerase I flank the deletion site in both sequences, suggesting an involvement of this enzyme during the deletion-recombination process.
Drechsler
M
M
Institute of Human Genetics, University of Heidelberg, Germany.
Royer-Pokora
B
B
D000595:Amino Acid Sequence; D015783:Aniridia / Q000235:genetics*; D001483:Base Sequence; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D003001:Cloning, Molecular; D004247:DNA; D004268:DNA-Binding Proteins / Q000235:genetics*; D005136:Eye Proteins; D018398:Homeodomain Proteins; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D016366:Open Reading Frames; D000071841:PAX6 Transcription Factor; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D016415:Sequence Alignment; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics
D004268:DNA-Binding Proteins; D005136:Eye Proteins; D018398:Homeodomain Proteins; D000071841:PAX6 Transcription Factor; C000605730:PAX6 protein, human; D051761:Paired Box Transcription Factors; D012097:Repressor Proteins; D014157:Transcription Factors; D004247:DNA