IDENTIFICATION OF THE HUMAN CHROMOSOMAL REGION CONTAINING THE IRIDOGONIODYSGENESIS ANOMALY LOCUS BY GENOMIC-MISMATCH SCANNING

Genome-mismatch scanning (GMS) is a new method of linkage analysis tha t rapidly isolates regions of identity between two genomes. DNA molecu les from regions of identity by descent from two relatives are isolate d based on their ability to form extended mismatch-free heteroduplexes . We have applied this rapid technology to identify the chromosomal re gion shared by two fifth-degree cousins with autosomal dominant iridog onio dysgenesis anomaly (IGDA), a rare ocular neurocristopathy. Marker s on the short arm of human chromosome Gp were recovered, consistent w ith the results of conventional linkage analysis conducted in parallel , indicating linkage of IGDA to 6p25. Control markers tested on a seco nd human chromosome were not recovered. A GMS error rate of similar to 11% was observed, well within an acceptable range for a rapid, first screening approach, especially since GMS results would be confirmed by family analysis with selected markers from the putative region of ide ntity by descent. These results demonstrate not only the value of this technique in the rapid mapping of human genetic traits, but the first application of GMS to a multicellular organism.