title: Candidate DNA replication initiation regions at human trinucleotide repeat disease loci.
abstract: The positions of DNA replication initiation regions (IRs) at three human trinucleotide repeat (TNR) disease loci were examined in order to characterize the role played by IRs in explaining the known locus-specific variation in TNR instability levels. Using three different normal cell lines, candidate IRs were identified at the HD, SCA-7 and SBMA loci. At each locus the IR is less than 3.6 kb from the CAG/CTG repeat tract. Preliminary studies with a cell line homozygous for an HD disease mutation indicated no change in the position of the candidate IR in spite of the mutation. Comparison with experimental results from model systems suggests that a complex relationship may exist between instability and the proximity and/or orientation of the repeats with respect to an IR.
authors.affiliation: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089-1340, USA.
authors.forename: Taurai
authors.initials: T
authors.lastname: Nenguke
authors.forename: Mirit I
authors.initials: MI
authors.lastname: Aladjem
authors.forename: James F
authors.initials: JF
authors.lastname: Gusella
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Wexler
authors.forename: Norman
authors.initials: N
authors.lastname: Arnheim
mesh_terms: D000067719:Ataxin-7; D004247:DNA / Q000378:metabolism; D030342:Genetic Diseases, Inborn; D006801:Humans; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D018741:Replication Origin; D019680:Trinucleotide Repeat Expansion
chemical_list: C000593829:ATXN7 protein, human; D000067719:Ataxin-7; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA