title: Fine structure DNA mapping studies of the chromosomal region harboring the genetic defect in neurofibromatosis type I.
abstract: To better map the location of the von Recklinghausen neurofibromatosis (NF1) gene, we have characterized a somatic cell hybrid designated 7AE-11. This microcell-mediated, chromosome-transfer construct harbors a centromeric segment and a neo-marked segment from the distal long arm of human chromosome 17. We have identified 269 cosmid clones with human sequences from a 7AE-11 library and, using a panel of somatic cell hybrids with a total of six chromosome 17q breakpoints, have mapped 240 of these clones on chromosome 17q. The panel included a hybrid (NF13) carrying a der(22) chromosome that was isolated from an NF1 patient with a balanced translocation, t(17;22) (q11.2;q11.2). Fifty-three of the cosmids map into a region spanning the NF13 breakpoint, as defined by the two closest flanking breakpoints (17q11.2 and 17q11.2-q12). RFLP clones from a subset of these cosmids have been mapped by linkage analysis in normal reference families, to localize the NF1 gene more precisely and to enhance the potential for genetic diagnosis of this disorder. The cosmids in the NF1 region will be an important resource for testing DNA blots of large-fragment restriction-enzyme digests from NF1 patient cell lines, to detect rearrangements in patients' DNA and to identify the 17;22 NF1 translocation breakpoint.
authors.affiliation: Howard Hughes Medical Institute, University of Utah Medical Center, Salt Lake City 84132.
authors.forename: P
authors.initials: P
authors.lastname: O'Connell
authors.forename: R J
authors.initials: RJ
authors.lastname: Leach
authors.forename: D H
authors.initials: DH
authors.lastname: Ledbetter
authors.forename: R M
authors.initials: RM
authors.lastname: Cawthon
authors.forename: M
authors.initials: M
authors.lastname: Culver
authors.forename: J R
authors.initials: JR
authors.lastname: Eldridge
authors.forename: A K
authors.initials: AK
authors.lastname: Frej
authors.forename: T R
authors.initials: TR
authors.lastname: Holm
authors.forename: E
authors.initials: E
authors.lastname: Wolff
authors.forename: M J
authors.initials: MJ
authors.lastname: Thayer
mesh_terms: D000818:Animals; D002460:Cell Line; D002871:Chromosome Banding; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D015342:DNA Probes; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D007621:Karyotyping; D009456:Neurofibromatosis 1 / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D051381:Rats
chemical_list: D015342:DNA Probes; D005819:Genetic Markers