Mapping of D4S98/S114/S113 confines the Huntington's defect to a reduced physical region at the telomere of chromosome 4.
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.
Whaley
W L
WL
Neurogenetics Laboratory, Massachusetts General Hospital, Boston.
Michiels
F
F
MacDonald
M E
ME
Romano
D
D
Zimmer
M
M
Smith
B
B
Leavitt
J
J
Bucan
M
M
Haines
J L
JL
Gilliam
T C
TC
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
D015342:DNA Probes; D005819:Genetic Markers