title: Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4.
abstract: The dominant gene defect in Huntington's disease (HD) is linked to the DNA marker D4S10, near the telomere of the chromosome 4 short arm. Two other markers, D4S43 and D4S95, are closer, but still proximal to the HD gene in 4p16.3. We have characterized a new locus, D4S114, identified by cloning the end of a NotI fragment resolved by pulsed-field gel electrophoresis. D4S114 was localized distal to D4S43 and D4S95 by both physical and genetic mapping techniques. The "end"-clone overlaps a previously isolated NotI "linking" clone, and is within 150 kb of a second "linking" clone defining D4S113. Restriction fragment length polymorphisms for D4S113 and D4S114, one of which is identical to a SacI polymorphism detected by the anonymous probe pBS731B-C (D4S98), were typed for key crossovers in HD and reference pedigrees. The data support the locus order D4S10-(D4S43, D4S95)-D4S98/S114/S113-HD-telomere. The D4S98/S114/S113 cluster therefore represents the nearest cloned sequences to HD, and provides a valuable new point for launching directional cloning strategies to isolate and characterize this disease gene.
authors.affiliation: Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
authors.forename: W L
authors.initials: WL
authors.lastname: Whaley
authors.forename: F
authors.initials: F
authors.lastname: Michiels
authors.forename: M E
authors.initials: ME
authors.lastname: MacDonald
authors.forename: D
authors.initials: D
authors.lastname: Romano
authors.forename: M
authors.initials: M
authors.lastname: Zimmer
authors.forename: B
authors.initials: B
authors.lastname: Smith
authors.forename: J
authors.initials: J
authors.lastname: Leavitt
authors.forename: M
authors.initials: M
authors.lastname: Bucan
authors.forename: J L
authors.initials: JL
authors.lastname: Haines
authors.forename: T C
authors.initials: TC
authors.lastname: Gilliam
mesh_terms: D000818:Animals; D002460:Cell Line; D002874:Chromosome Mapping; D002894:Chromosomes, Human, Pair 4; D006224:Cricetinae; D015342:DNA Probes; D005819:Genetic Markers / Q000032:analysis*; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D008126:Lod Score; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D015342:DNA Probes; D005819:Genetic Markers