© 1992 Oxford University Press
RESEARCH-ARTICLE |
Characterization of a 1.0 Mb YAC contig spannning two chromosome breakpoints related to Menkes disease
1The John F.Kennedy Institute GI.Landevej 7, 2600 Glostrup, Denmark 2The Danish Center for Human Genome Research GI.Landevej 7, 2600 Glostrup, Denmark 3ICRF Laboratories, Institute of Molecular Medicine, John Radcliffe Hospital Headington, Oxford Ox3 9DU, UK 4Department of Medical Genetics, Ullevaal Hospital Oslo, Norway
*To whom correspondence should be addressed
Received July 16, 1992; Revised August 24, 1992; Accepted August 24, 1992
Menkes disease, an X-linked recessive disorder of copper metabolism, has recently been mapped to Xq13.3 by two Menkes patients carrying chromosome rearrangements within this region. The breakpoints have been investigated by nonisotopic in situ suppression hybridization using YACs isolated from this region with the flanking markers DXS56 and PGK1. Three YACs were extending over the breakpoints at Xq 13.3 and were shown to be overlapping by partial digest restriction maps, IRS-PCR fingerprinting and by the presence of common cosmid clones. These cosmids were subcloned and one of the single copy probes detected both breakpoints using rare-cutting restriction enzyme digests of the patients. All the results together localize the breakpoints to about 100 kb within the overlapping region of the YACs. Mapping of both breakpoints in a 1 Mb YAC contig implies that these YACs contain at least partially, the gene responsible for Menkes disease.