Abstract

Hereditary ataxias are a group of diseases which include spinocerebellar degenerations and olivopontocerebellar atrophies. The Schut-Swier kindred has an autosomal dominant form of spinocerebellar ataxia (SCA) genetically linked to the HLA complex chromosome 6. DNA markers will be isolated from chromosome 6 which permit the delection of polymorphic restriction endonuclease sites in the Schut-Swier kindred. These markers will be mapped to sub-regions along chromosome 6. A panel of mapped markers will then be used to probe genomic DNA from lymphoblastoid cell lines established from 80 members of the Schut-Swier kindred. These data will be analyzed for restriction fragments linked to the SCA gene. The establishment of a linked marker(s) to SCA will permit: 1) The identification of individuals carrying the SCA gene within the Schut-Swier kindred. This information will enable more precise genetic counseling. Members of this kindred have proven to be very responsive to past counseling by Dr. Schut. 2) Determining if SCA in other kindreds is due to a mutation in the same locus as the Schut-Swier kindred, 3) The use of molecular biological methods to isolate and characterize the SCA gene.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS022920-02
Application #
3405739
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
2
Fiscal Year
1987
Total Cost
Indirect Cost

  Institution

Name
University of Minnesota Twin Cities
Department
Type
Schools of Medicine
DUNS #
168559177
City
Minneapolis
State
MN
Country
United States
Zip Code
55455

  Publications

Rubinsztein, David C; Orr, Harry T (2016) Diminishing return for mechanistic therapeutics with neurodegenerative disease duration?: There may be a point in the course of a neurodegenerative condition where therapeutics targeting disease-causing mechanisms are futile. Bioessays 38:977-80
Nelson, David L; Orr, Harry T; Warren, Stephen T (2013) The unstable repeats--three evolving faces of neurological disease. Neuron 77:825-43
Ebner, Blake A; Ingram, Melissa A; Barnes, Justin A et al. (2013) Purkinje cell ataxin-1 modulates climbing fiber synaptic input in developing and adult mouse cerebellum. J Neurosci 33:5806-20
Orr, Harry T (2012) Cell biology of spinocerebellar ataxia. J Cell Biol 197:167-77
Ingram, Melissa A C; Orr, Harry T; Clark, H Brent (2012) Genetically engineered mouse models of the trinucleotide-repeat spinocerebellar ataxias. Brain Res Bull 88:33-42
Orr, Harry T (2012) Polyglutamine neurodegeneration: expanded glutamines enhance native functions. Curr Opin Genet Dev 22:251-5
Fryer, John D; Yu, Peng; Kang, Hyojin et al. (2011) Exercise and genetic rescue of SCA1 via the transcriptional repressor Capicua. Science 334:690-3
Gehrking, Kristin M; Andresen, J Michael; Duvick, Lisa et al. (2011) Partial loss of Tip60 slows mid-stage neurodegeneration in a spinocerebellar ataxia type 1 (SCA1) mouse model. Hum Mol Genet 20:2204-12
Oz, Gülin; Vollmers, Manda L; Nelson, Christopher D et al. (2011) In vivo monitoring of recovery from neurodegeneration in conditional transgenic SCA1 mice. Exp Neurol 232:290-8
Barnes, Justin A; Ebner, Blake A; Duvick, Lisa A et al. (2011) Abnormalities in the climbing fiber-Purkinje cell circuitry contribute to neuronal dysfunction in ATXN1[82Q] mice. J Neurosci 31:12778-89

Showing the most recent 10 out of 62 publications