Closing in on the Rieger syndrome gene on 4q25: mapping translocation breakpoints within a 50-kb region. Am J Hum Genet 1996 Dec;59(6):1297-305
Date
12/01/1996Pubmed ID
8940275Pubmed Central ID
PMC1914859Scopus ID
2-s2.0-19244364120 (requires institutional sign-in at Scopus site) 25 CitationsAbstract
Rieger syndrome (RGS) is an autosomal dominant disorder of morphogenesis affecting mainly the formation of the anterior eye chamber and of the teeth. RGS has been localized to human chromosome 4q25 by linkage to epidermal growth factor (EGF). We have constructed a detailed physical map and a YAC contig of the genomic region encompassing the EGF locus. Using FISH, several YACs could be shown to cross the breakpoint in two independent RGS patients with balanced 4q translocations. Alu- and LINE-fragmentation of a 2.4-Mb YAC generated a panel of shorter YACs ranging in size from 2.4 Mb to 75 kb. Several fragmentation YACs were subcloned in cosmids, which were mapped to specific subregions of the original YAC by hybridization to the fragmentation panel to further refine the localization of the translocation breakpoints, allowing mapping of the breakpoints to within the most-telomeric 200 kb of the original 2.4-Mb YAC. FiberFISH of cosmids located in this 200-kb region mapped the two translocation breakpoints within a 50-kb region approximately 100-150 kb centromeric to D4S193, significantly narrowing down the candidate region for RGS. The mapping data and resources reported here should facilitate the identification of a gene implicated in Rieger syndrome.
Author List
Datson NA, Semina E, van Staalduinen AA, Dauwerse HG, Meershoek EJ, Heus JJ, Frants RR, den Dunnen JT, Murray JC, van Ommen GJAuthor
Elena V. Semina PhD Chief, Professor in the Ophthalmology and Visual Sciences department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Blotting, SouthernCell Line
Chromosome Mapping
Chromosomes, Human, Pair 4
Craniofacial Abnormalities
Glaucoma
Humans
In Situ Hybridization, Fluorescence
Polymerase Chain Reaction
Syndrome
Tooth Abnormalities
Translocation, Genetic
Umbilicus