Abstract

The region Xp21 of the human genome will reduced to an ordered array of cloned DNA segments by chromosome """"""""walking"""""""" from multiple start points from within the region. The locus responsible for Duchenne muscular dystrophy known to lie within Xp21 will be identified and the product encoded by this locus characterized. The manner in which the product of the DMD locus is altered in patients will be determined by direct analysis of the DNA of the affected individuals. Mutations which disrupt normal function will be used as indicators of where the normal product from the locus functions. Structural characteristics of the Xp21 region which might affect normal expression from the locus will be studied with special emphasis given to possible mutational instablity of the region. The genetic distance of the entire region will be precisely determined and meiotic exchange points identified. Accurate prediction of individuals at risk for the disease will result by either direct analysis of the locus or indirect analysis with tightly linked markers. Ultimately, the pathways in neuromuscular development will be identified which are altered in Duchenne muscular dystrophy patients and possibly patients with other neuromuscular diseases.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023740-04
Application #
3407557
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1986-07-01
Project End
1991-06-30
Budget Start
1989-07-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Children's Hospital Boston
Department
Type
DUNS #
076593722
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Bonnemann, C G; Wong, J; Jones, K J et al. (2002) Primary gamma-sarcoglycanopathy (LGMD 2C): broadening of the mutational spectrum guided by the immunohistochemical profile. Neuromuscul Disord 12:273-80
Peters, M F; Sadoulet-Puccio, H M; Grady, M R et al. (1998) Differential membrane localization and intermolecular associations of alpha-dystrobrevin isoforms in skeletal muscle. J Cell Biol 142:1269-78
Scharf, J M; Endrizzi, M G; Wetter, A et al. (1998) Identification of a candidate modifying gene for spinal muscular atrophy by comparative genomics. Nat Genet 20:83-6
Chan, Y; Tong, H Q; Beggs, A H et al. (1998) Human skeletal muscle-specific alpha-actinin-2 and -3 isoforms form homodimers and heterodimers in vitro and in vivo. Biochem Biophys Res Commun 248:134-9
Bonnemann, C G; Wong, J; Ben Hamida, C et al. (1998) LGMD 2E in Tunisia is caused by a homozygous missense mutation in beta-sarcoglycan exon 3. Neuromuscul Disord 8:193-7
Peters, M F; O'Brien, K F; Sadoulet-Puccio, H M et al. (1997) beta-dystrobrevin, a new member of the dystrophin family. Identification, cloning, and protein associations. J Biol Chem 272:31561-9
Carter, T A; Bonnemann, C G; Wang, C H et al. (1997) A multicopy transcription-repair gene, BTF2p44, maps to the SMA region and demonstrates SMA associated deletions. Hum Mol Genet 6:229-36
Gussoni, E; Blau, H M; Kunkel, L M (1997) The fate of individual myoblasts after transplantation into muscles of DMD patients. Nat Med 3:970-7
Sadoulet-Puccio, H M; Feener, C A; Schaid, D J et al. (1997) The genomic organization of human dystrobrevin. Neurogenetics 1:37-42
Sadoulet-Puccio, H M; Rajala, M; Kunkel, L M (1997) Dystrobrevin and dystrophin: an interaction through coiled-coil motifs. Proc Natl Acad Sci U S A 94:12413-8

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