Chromosome Jumping from D4S10 (G8) toward the Huntington Disease Gene

The gene for Huntington disease (HD) has been localized to the distal portion of the short arm of human chromosome 4 by linkage analysis. Currently, the two closest DNA markers are D4S10 (G8), located ≈ 3 centimorgans centromeric to HD, and D4S43 (C4H), positioned 0-1.5 centimorgans from HD. In an e...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1988-09, Vol.85 (17), p.6437-6441
Main Authors: Richards, Julia E., Gilliam, T. Conrad, Cole, Jeffery L., Drumm, Mitchell L., Wasmuth, John J., Gusella, James F., Collins, Francis S.
Format: Article
Language:English
Subjects:
Bacteriophages
Biological and medical sciences
Cell Line
Chromosome Mapping
Chromosomes
Chromosomes, Human, Pair 4
Cloning, Molecular
Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases
DNA
Electrophoresis
Gels
Genes
Genetic loci
Humans
Huntington disease
Huntington Disease - genetics
Libraries
Ligation
Medical sciences
Neurology
Polymorphism, Restriction Fragment Length
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Summary:The gene for Huntington disease (HD) has been localized to the distal portion of the short arm of human chromosome 4 by linkage analysis. Currently, the two closest DNA markers are D4S10 (G8), located ≈ 3 centimorgans centromeric to HD, and D4S43 (C4H), positioned 0-1.5 centimorgans from HD. In an effort to move closer to the HD gene, with the eventual goal of identifying the gene itself, we have applied the technique of chromosome jumping to this region. A 200-kilobase jumping library has been constructed, and a jump from D4S10 has been obtained and its approximate distance verified by pulsed field gel electrophoresis. Two restriction fragment length polymorphisms have been identified at the jump locus, which is denoted D4S81. Linkage analysis of previously identified recombinants between D4S10 and HD or D4S10 and D4S43 shows that in two of five events the jump has crossed the recombination points. This unequivocally orients D4S10 and D4S81 on the chromosome, provides additional markers for HD, and suggests that recombination frequency in this region of chromosome 4 may be increased, so that the physical distance from D4S10 to HD may not be as large as originally suspected.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.85.17.6437