This Program Project involves clinical neurology, genetic linkage analyses and molecular genetic techniques and strategies to study genetic neurological disorders that are at different stages of genetic research. The Project involves six projects and one Core. Project 1 describes diagnostic evaluations, DNA collection, and general linkage analyses for several diseases for which the genetic locus is unknown including non-Duffy-linked Charcot-Marie-Tooth Disease Type 1, vestibular periodic ataxia, autosomal dominant limb girdle muscular dystrophy, oculopharyngeal muscular dystrophy and facio humeral muscular dystrophy. Project 2 proposes continued clinical and linkage studies in tuberous sclerosis, a phakomatous disease for which a tentative locus has been suggested but not proven. Project 3 proposes fine chromosome mapping for two phakomatous diseases, neurofibromatosis and von Hippel-Lindau disease, for which the regional location of the chromosome loci have been established. Project 4 proposes to continue the family development and general linkage analysis for inherited spinal muscular atrophies and other inherited motor neuron diseases, and proposes subtraction hybridization strategies to provide candidate genes. Project 5 describes detailed gene analyses, including characterization of the deletion mutations in Duchenne muscular dystrophy as well as a genetic analysis of the site of mutations, and to study patterns of expression of the DMD gene product in DMD carriers and in a new canine model with deletion of the dystrophin gene. Project 6 proposes to use molecular genetic strategies to define putative antigens in autoimmune myasthenia gravis patients that directly correlate with the pathogenesis and severity of disease, as well as proposing to initiate family genetic studies to determine possible genetic factors that influence the expression of the disease. Core Unit A provides the overall data management and contains the DNA banking facility for the various projects.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Program Projects (P01)
Project #
5P01NS026630-02
Application #
3100240
Study Section
Special Emphasis Panel (SRC (01))
Project Start
1989-01-01
Project End
1993-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
2
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
Griswold, Anthony J; Van Booven, Derek; Cuccaro, Michael L et al. (2018) Identification of rare noncoding sequence variants in gamma-aminobutyric acid A receptor, alpha 4 subunit in autism spectrum disorder. Neurogenetics 19:17-26
Zhu, Zuobin; Lu, Xitong; Yuan, Dejian et al. (2017) Close genetic relationships between a spousal pair with autism-affected children and high minor allele content in cases in autism-associated SNPs. Genomics 109:9-15
Correia, Catarina; Oliveira, Guiomar; Vicente, Astrid M (2014) Protein interaction networks reveal novel autism risk genes within GWAS statistical noise. PLoS One 9:e112399
Gaugler, Trent; Klei, Lambertus; Sanders, Stephan J et al. (2014) Most genetic risk for autism resides with common variation. Nat Genet 46:881-5
Hadjixenofontos, Athena; Schmidt, Michael A; Whitehead, Patrice L et al. (2013) Evaluating mitochondrial DNA variation in autism spectrum disorders. Ann Hum Genet 77:9-21
Anney, Richard; Klei, Lambertus; Pinto, Dalila et al. (2012) Individual common variants exert weak effects on the risk for autism spectrum disorders. Hum Mol Genet 21:4781-92
Cukier, Holly N; Lee, Joycelyn M; Ma, Deqiong et al. (2012) The expanding role of MBD genes in autism: identification of a MECP2 duplication and novel alterations in MBD5, MBD6, and SETDB1. Autism Res 5:385-97
Griswold, Anthony J; Ma, Deqiong; Cukier, Holly N et al. (2012) Evaluation of copy number variations reveals novel candidate genes in autism spectrum disorder-associated pathways. Hum Mol Genet 21:3513-23
Casey, Jillian P; Magalhaes, Tiago; Conroy, Judith M et al. (2012) A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder. Hum Genet 131:565-79
Cuccaro, Michael L; Tuchman, Roberto F; Hamilton, Kara L et al. (2012) Exploring the relationship between autism spectrum disorder and epilepsy using latent class cluster analysis. J Autism Dev Disord 42:1630-41

Showing the most recent 10 out of 204 publications