Our long-term objective is to construct a 5 centiMorgan resolution genetic linkage map of the human genome. This would provide a valuable resource which we intend to make available to interested investigators for mapping and cloning genes responsible for Mendelian disorders. In addition, the availability of a genetic map would facilitate construction of a physical map of the human genome.
The specific aims of this project are to 1) fill in gaps in our current map by identifying new polymorphisms from chromosome specific libraries and by incorporating RFLPs identified by other researchers into the existing map, 2) establish the physical end points of the existing linkage groups by in situ hybridization of the most distal markers, and extend the maps to the ends of the chromosomes by incorporating RFLPs known to lie in these regions or by identifying new RFLPs near known distal nonpolymorphic DNA segments, 3) define and develop subsets of RFLP markers (""""""""genome kits"""""""") that will provide adequate coverage of each chromosome for efficient future genetic mapping of disease causing agents, 4) define and develop a panel of RFLP markers suited for identification of chromosome deletions through the loss of heterozygosity of RFLP alleles, and 5) covert the CRI-MAP multilocus linkage analysis computer program package into a form for general use, and begin development of programs to test the """"""""simultaneous search"""""""" method proposed by Lander and Botstein (1987) for identification of multiple genes implicated in complex or heterogeneous disorders. Development of the map and related resources would 1) identify immediately the chromosomal location of new linkages, 2) enable development of more accurate informative tests for presymptomatic diagnosis of genetic diseases, 3) enable searches for and cloning of disease causing genes to be conducted in a more efficient manner, 4) make it possible to map complex genetic disorders, and 5) allow one to detect and define the limits of chromosomal specific deletions that are characteristic of some neoplastic disorders. In the long-term, the genetic map and related resources will likely prove instrumental in developing a better understanding of the molecular genetic mechanism underlying many diseases, and ultimately improved therapeutic approaches for treatment or cure.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
3R01HG000304-04S1
Application #
3333368
Study Section
Special Emphasis Panel (SSS)
Project Start
1989-01-01
Project End
1993-06-30
Budget Start
1991-09-30
Budget End
1993-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Iannotti, C A; Inoue, H; Bernal, E et al. (1997) Identification of a human LMX1 (LMX1.1)-related gene, LMX1.2: tissue-specific expression and linkage mapping on chromosome 9. Genomics 46:520-4
Aoki, M; Koranyi, L; Riggs, A C et al. (1996) Identification of trinucleotide repeat-containing genes in human pancreatic islets. Diabetes 45:157-64
Lindberg, F P; Lublin, D M; Telen, M J et al. (1994) Rh-related antigen CD47 is the signal-transducer integrin-associated protein. J Biol Chem 269:1567-70
Kaufman, B A; White, P S; Steinbrueck, T et al. (1994) Linkage mapping of the tumor necrosis factor receptor 2 (TNFR2) gene to 1p36.2 using the single-strand conformation polymorphism technique. Hum Genet 94:418-22
York, J D; Majerus, P W (1994) Nuclear phosphatidylinositols decrease during S-phase of the cell cycle in HeLa cells. J Biol Chem 269:7847-50
Tanizawa, Y; Riggs, A C; Elbein, S C et al. (1994) Human glucagon-like peptide-1 receptor gene in NIDDM. Identification and use of simple sequence repeat polymorphisms in genetic analysis. Diabetes 43:752-7
Norris, F A; Majerus, P W (1994) Hydrolysis of phosphatidylinositol 3,4-bisphosphate by inositol polyphosphate 4-phosphatase isolated by affinity elution chromatography. J Biol Chem 269:8716-20
Tanizawa, Y; Riggs, A C; Dagogo-Jack, S et al. (1994) Isolation of the human LIM/homeodomain gene islet-1 and identification of a simple sequence repeat polymorphism [corrected] Diabetes 43:935-41
Howe, J R; Lairmore, T C; Veile, R et al. (1993) Development of a sequence-tagged site for the centromere of chromosome 10: its use in cytogenetic and physical mapping. Hum Genet 91:199-204
Crouch, E; Rust, K; Veile, R et al. (1993) Genomic organization of human surfactant protein D (SP-D). SP-D is encoded on chromosome 10q22.2-23.1. J Biol Chem 268:2976-83

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