Myotonic muscular dystrophy (DM) is the most common form of genetic muscular dystrophy affecting adults and children. The gene for DM is located near the centromere on chromosome 19. DM and apolipoprotein C11 (apoC11) have been closely linked using two apoC11 DNA polymorphisms to test linkage in our large, multigenerational DM pedigrees. Several new anonymous restriction fragment length polymorphisms (RFLPs) have been isolated from chromosome 19 enriched libraries and are being tested for linkage to DM. We propose to continue to identify tightly linked RFLPs and to initiate chromosome walking to define the DM gene. We propose to use enriched chromosome 19 libraries prepared in phages EMBL3 and charon 35, and the LORIST vector for the chromosome walk, initiating at the tightest available DNA probe. LORIST has the advantage over other cosmid vectors in that it maintains a higher and more constant copy number with large insert size, and can rapidly discriminate the opposing ends of the insert facilitating rapid direction specific chromosome walks. We propose to map chromosome 19 in the area of DM and to identify the DM gene using multiple strategies. Our goal is to design rational treatments of DM, perhaps taking advantage of the variable expressivity and penetrance that characterize this late-age-of-onset disorder to prevent symptoms and signs in presymptomatic heterozygotes.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019999-08
Application #
3400157
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1983-07-01
Project End
1992-03-31
Budget Start
1990-08-01
Budget End
1992-03-31
Support Year
8
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Duke University
Department
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Samson, F; Mesnard, L; Mihovilovic, M et al. (1994) A new human slow skeletal troponin T (TnTs) mRNA isoform derived from alternative splicing of a single gene. Biochem Biophys Res Commun 199:841-7
Roses, A D (1993) Molecular genetics of neurodegenerative diseases. Curr Opin Neurol Neurosurg 6:34-9
Speer, M C; Yamaoka, L H; Gilchrist, J H et al. (1992) Confirmation of genetic heterogeneity in limb-girdle muscular dystrophy: linkage of an autosomal dominant form to chromosome 5q. Am J Hum Genet 50:1211-7
Kazantsev, A; Yamaoka, L H; Roses, A D (1992) A dinucleotide repeat polymorphism in the human Na+,K+ ATPase, alpha subunit (ATP1A3) gene. Nucleic Acids Res 20:1164
Samson, F; de Jong, P J; Trask, B J et al. (1992) Assignment of the human slow skeletal troponin T gene to 19q13.4 using somatic cell hybrids and fluorescence in situ hybridization analysis. Genomics 13:1374-5
Gilbert, J R; Stajich, J M; Speer, M C et al. (1992) Linkage studies in facioscapulohumeral muscular dystrophy (FSHD). Am J Hum Genet 51:424-7
Samson, F; Gilbert, J R; Koza-Taylor, P et al. (1991) A PstI polymorphism detected by a genomic clone at the human slow troponin T (TNNT1) gene locus. Nucleic Acids Res 19:6058
Secore, S L; Walker, A P; Herbstreith, M H et al. (1991) A StuI polymorphism on chromosome 3p14.1-14.2 (D3S622) defined by two polymorphic StuI sites 2.4 kb apart. Nucleic Acids Res 19:6349
Speer, M C; Pericak-Vance, M A; Yamaoka, L et al. (1990) Presymptomatic and prenatal diagnosis in myotonic dystrophy by genetic linkage studies. Neurology 40:671-6
Roses, A D; Pericak-Vance, M A; Clark, C M et al. (1990) Linkage studies of late-onset familial Alzheimer's disease. Adv Neurol 51:185-96

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