This program is designed to provide facilities and resources for human genetic mapping in Johns Hopkins University, to develop 2 technical approaches to mapping, and to conduct mapping studies of specific skeletal, neurologic, and ophthalmologic disorders and of a developmental regulatory gene locus. A facility for establishing lymphoblastoid cell lines, preparing DNA, and banking both will also serve as a repository for probes and restriction enzymes and will provide the service of gene localization by in situ hybridization and hybridization to DNAs from panels of somatic cell hybrids. The Lancaster County Amish, in whom studies have been going on by members of this department for over 25 years, will be further developed as a resource for family linkage studies. Facilities for genetic data management and analysis, particularly of family linkage data, will be developed. Technical projects will be concerned with cloning large DNA segments in yeast artificial chromosomes (YAC) and will provide a new method for detecting polymorphism based on polymerase chain reaction. By genetic and physical approaches, interference to crossingover in the pericentromeric regions will be evaluated quantitatively. A locus that controls the level of hemoglobin F, called FCP (F-cell production), appears to be on Xq. This locus will be mapped and cloning will be attempted. Multiple exostoses (and the trichorhinophalangeal syndrome), which may be on chromosome 8, will be investigated by family linkage methods. The related Langer- Giedion syndrome will be investigated by cloning of the deleted portion of 8q24. The nail-patella syndrome, which is located in 9q34 very close to adenylate kinase-1 and moderately close to ABO, will be studied by candidate gene and cloning approaches. By family linkage studies, the map location of 2 skeletal dysplasias of unknown biochemical cause, Ellis-van Creveld syndrome and cartilage-hair hypoplasia, will be determined as the first step toward to defining basic pathogenesis. Mapping of three neurologic disorders - - Charcot-Marie-Tooth disease (CMT), Gilles de la Tourette syndrome (GTS) and Werdnig-Hoffman (WH) disease -- will be studied by the family linkage approach (first 2) and by homozygosity mapping in offspring of consanguineous parents (the last). The gene that is mutant in Norrie disease will be sought by cloning experiments in case(s) of deletion of Xp11. The core facilities will assist other mapping studies by the members of the departments of psychiatry, ophthalmology, and neurology. The facilities will also make it possible for rapid mapping of the mRNAs being isolated in several laboratories as contributions to the cDNA map of the human genome.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM041015-02
Application #
3096380
Study Section
(SSS)
Project Start
1988-09-29
Project End
1993-08-31
Budget Start
1989-09-01
Budget End
1990-08-31
Support Year
2
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Pyeritz, R E (1993) Marfan syndrome: current and future clinical and genetic management of cardiovascular manifestations. Semin Thorac Cardiovasc Surg 5:11-6
DiLella, A G; Hawkins, A; Craig, R J et al. (1992) Chromosomal band assignments of the genes encoding human FKBP12 and FKBP13. Biochem Biophys Res Commun 189:819-23
Amelung, P J; Panhuysen, C I; Postma, D S et al. (1992) Atopy and bronchial hyperresponsiveness: exclusion of linkage to markers on chromosomes 11q and 6p. Clin Exp Allergy 22:1077-84
Dietz, H C; Pyeritz, R E; Puffenberger, E G et al. (1992) Marfan phenotype variability in a family segregating a missense mutation in the epidermal growth factor-like motif of the fibrillin gene. J Clin Invest 89:1674-80
Dietz, H C; Saraiva, J M; Pyeritz, R E et al. (1992) Clustering of fibrillin (FBN1) missense mutations in Marfan syndrome patients at cysteine residues in EGF-like domains. Hum Mutat 1:366-74
Montrose-Rafizadeh, C; Blackmon, D L; Hamosh, A et al. (1992) Regulation of cystic fibrosis transmembrane conductance regulator (CFTR) gene transcription and alternative RNA splicing in a model of developing intestinal epithelium. J Biol Chem 267:19299-305
Finkelstein, J E; Doege, K; Yamada, Y et al. (1991) Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia. Am J Hum Genet 48:97-102
Jabs, E W; Warren, A C; Taylor, E W et al. (1991) Alphoid DNA polymorphisms for chromosome 21 can be distinguished from those of chromosome 13 using probes homologous to both. Genomics 9:141-6
Jabs, E W; Coss, C A; Hayflick, S J et al. (1991) Chromosomal deletion 4p15.32----p14 in a Treacher Collins syndrome patient: exclusion of the disease locus from and mapping of anonymous DNA sequences to this region. Genomics 11:188-92
Petersen, M B; Adelsberger, P A; Schinzel, A A et al. (1991) Down syndrome due to de novo Robertsonian translocation t(14q;21q): DNA polymorphism analysis suggests that the origin of the extra 21q is maternal. Am J Hum Genet 49:529-36

Showing the most recent 10 out of 14 publications