Recombinant DNA technology has provided a new and abundant source of powerful genetic linkage markers in the form of restriction fragment length polymorphisms (RFLPs). The possibility of deriving a complete genetic linkage map of the human genome is now an achievable goal. We propose to use 3 large pedigrees from which many lymphoblastoid cell lines are already available as reference pedigrees for determining the linkage relationships of the new RFLP markers generated both by ourselves and by others. DNA from lymphoblast lines derived by transformation with Epstein-Barr virus will be prepared for all informative members of these pedigrees. It will then be digested with restriction enzymes, fractionated by agarose gel electrophoresis, transferred to a solid filter support, and probed with cloned human DNA fragments known to reveal polymorphisms. The genotype of an individual at a given locus will then be determined by examining the pattern of fragments detected by a hybridization probe from that locus. The linkage relationships of different RFLP markers will be examined using the LIPED computer program and, when appropriate, a Multi-point Mapping program. The genetic map which will be constructed using this data will have profound implications for all human genetic disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020012-03
Application #
3400172
Study Section
Genetics Study Section (GEN)
Project Start
1983-07-01
Project End
1986-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
Whaley, W L; Bates, G P; Novelletto, A et al. (1991) Mapping of cosmid clones in Huntington's disease region of chromosome 4. Somat Cell Mol Genet 17:83-91
Siddique, T; Figlewicz, D A; Pericak-Vance, M A et al. (1991) Linkage of a gene causing familial amyotrophic lateral sclerosis to chromosome 21 and evidence of genetic-locus heterogeneity. N Engl J Med 324:1381-4
Fontaine, B; Hanson, M P; VonSattel, J P et al. (1991) Loss of chromosome 22 alleles in human sporadic spinal schwannomas. Ann Neurol 29:183-6
Brown Jr, R H; Horvitz, H R; Rouleau, G A et al. (1991) Gene linkage in familial amyotrophic lateral sclerosis: a progress report. Adv Neurol 56:215-26
Ramesh, V; Gusella, J F; Shih, V E (1991) Molecular pathology of gyrate atrophy of the choroid and retina due to ornithine aminotransferase deficiency. Mol Biol Med 8:81-93
Tzall, S; Martiniuk, F; Ozelius, L et al. (1991) Further characterization of PstI RFLPs at the acid alpha glucosidase (GAA) locus. Nucleic Acids Res 19:1727
Allitto, B A; MacDonald, M E; Bucan, M et al. (1991) Increased recombination adjacent to the Huntington disease-linked D4S10 marker. Genomics 9:104-12
Fontaine, B; Rouleau, G A; Seizinger, B R et al. (1991) Molecular genetics of neurofibromatosis 2 and related tumors (acoustic neuroma and meningioma). Ann N Y Acad Sci 615:338-43
Haines, J L; Amos, J; Attwood, J et al. (1991) Genetic heterogeneity in tuberous sclerosis. Study of a large collaborative dataset. Ann N Y Acad Sci 615:256-64
Fontaine, B; Sanson, M; Delattre, O et al. (1991) Parental origin of chromosome 22 loss in sporadic and NF2 neuromas. Genomics 10:280-3

Showing the most recent 10 out of 64 publications