title: A linkage study with DNA markers (D4S95, D4S115, and D4S111) in Japanese Huntington disease families.
abstract: Attempts to isolate the Huntington disease (HD) gene based on its position have been frustrated by apparently contradictory recombination events in HD pedigrees that have predicted two non-overlapping candidate regions: 100 kb at the telomere of the short arm of chromosome 4, and a 2.2 Mb region located internally at 4p16.3. The proximal location is also supported by the detection of a linkage disequilibrium between HD and some restriction fragment length polymorphisms (RFLPs) at the D4S95, D4S98, and D4S127 loci. In the present study, a proximal marker D4S95 showed tight linkage to the disease locus in Japanese pedigrees (Zmax = 3.31, theta max = 0.00), while distal markers D4S115 and D4S111 did not. Particularly, a two point linkage analysis between D4S111 and HD yielded a lod score -2.01 for theta = 0.015. This result leads to the exclusion, as a possible region of localization of the HD gene, of more than 3 cM of the genome around D4S111 locus. At the same time our results favor aforementioned proximal location as a candidate location for the HD gene.
authors.affiliation: Department of Neurology, University of Tokyo, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Watanabe
authors.forename: I
authors.initials: I
authors.lastname: Kondo
authors.forename: S
authors.initials: S
authors.lastname: Nissato
authors.forename: A
authors.initials: A
authors.lastname: Wakisaka
authors.forename: T
authors.initials: T
authors.lastname: Toda
authors.forename: J
authors.initials: J
authors.lastname: Ikeda
authors.forename: J J
authors.initials: JJ
authors.lastname: Wasmuth
authors.forename: J F
authors.initials: JF
authors.lastname: Gusella
authors.forename: I
authors.initials: I
authors.lastname: Kanazawa
mesh_terms: D000328:Adult; D000483:Alleles; D044466:Asian People; D002874:Chromosome Mapping; D005192:Family Health; D008040:Genetic Linkage; D005819:Genetic Markers / Q000235:genetics*; D016678:Genome; D006801:Humans; D006816:Huntington Disease / Q000235:genetics*; D007564:Japan; D015810:Linkage Disequilibrium; D008875:Middle Aged; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005819:Genetic Markers