We propose to establish a complete linkage map in the nematode Caenorhabditis elegans based on restriction fragment length polymorphisms (RFLPs). We intend to focus especially on those RFLPs generated by transposable elements (Tc1 and Tc2). The linkage map will then be used to map quantitative trait loci (QTLs) specifying life span and other life history traits. Subsequent integration of the RFLP map with extant physical and genetic maps will allow simultaneous positioning of QTLs onto genetic maps, making possible the directed construction of stocks showing specific variations in life span and other life history traits, and will simplify the eventual molecular characterization of genes specifying these traits. Although such positioning has been a theoretical possibility for several years, four new developments make the project feasible and of considerable importance: (1) the construction of overlapping arrays of contiguous DNA sequences or """"""""contigs"""""""" [Coulson et al. (1988) Nature, 335:184.]; (2) an effective mathematical algorithm for assigning QTLs to various physical regions (Lander and Botstein (1989) Genetics, 121:185] which has already been used to map QTLs in the tomato [Paterson et al. (1988) Nature, 335:721); (3) the development of recombinant inbred (RI) lines in the nematode C. elegans [Johnson (1987) Proc. Natl. Acad. Sci. USA, 84:3777]; and (4) a procedure for resolving genomic restriction digests on 2-D gels that may allow the simultaneous scoring of hundreds of RFLPs [Uitterlinden et al. (1989) Proc. Natl. Acad. Sci. USA, 86:2742].

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG010248-01
Application #
3122195
Study Section
Special Emphasis Panel (SSS (A))
Project Start
1991-06-01
Project End
1994-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
1
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of Colorado at Boulder
Department
Type
Other Domestic Higher Education
DUNS #
City
Boulder
State
CO
Country
United States
Zip Code
80309
Johnson, Thomas E (2005) Genes, phenes, and dreams of immortality: the 2003 Kleemeier Award lecture. J Gerontol A Biol Sci Med Sci 60:680-7
van Swinderen, B; Shook, D R; Ebert, R H et al. (1997) Quantitative trait loci controlling halothane sensitivity in Caenorhabditis elegans. Proc Natl Acad Sci U S A 94:8232-7
Johnson, T E (1997) Genetic influences on aging. Exp Gerontol 32:11-22
Shook, D R; Brooks, A; Johnson, T E (1996) Mapping quantitative trait loci affecting life history traits in the nematode Caenorhabditis elegans. Genetics 142:801-17
Johnson, T E; Lithgow, G J; Murakami, S (1996) Hypothesis: interventions that increase the response to stress offer the potential for effective life prolongation and increased health. J Gerontol A Biol Sci Med Sci 51:B392-5
Melov, S; Lithgow, G J; Fischer, D R et al. (1995) Increased frequency of deletions in the mitochondrial genome with age of Caenorhabditis elegans. Nucleic Acids Res 23:1419-25
Fabian, T J; Johnson, T E (1995) Total RNA, rRNA and poly(A)+RNA abundances during aging in Caenorhabditis elegans. Mech Ageing Dev 83:155-70
Duhon, S A; Johnson, T E (1995) Movement as an index of vitality: comparing wild type and the age-1 mutant of Caenorhabditis elegans. J Gerontol A Biol Sci Med Sci 50:B254-61
Lithgow, G J; White, T M; Melov, S et al. (1995) Thermotolerance and extended life-span conferred by single-gene mutations and induced by thermal stress. Proc Natl Acad Sci U S A 92:7540-4
Melov, S; Hertz, G Z; Stormo, G D et al. (1994) Detection of deletions in the mitochondrial genome of Caenorhabditis elegans. Nucleic Acids Res 22:1075-8

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