The goal of the current study is the generation of a map of the mouse genome in which all chromosomes are marked by loci, spaced approximately ten map units apart. These loci should be characterized by polymorphic variation, such that any given pair of strains which do not have a recent inbreeding history have different alleles at about half the loci. The single type of genetic marker which could fulfill these requirements is the restriction fragment length polymorphism in mouse DNA. We plan to map these variants using a variety of mapping techniques. The main emphasis will be on use of recombinant inbred strains. Other techniques will involve somatic hybrids segregating mouse chromosomes, the classical backcross and congenic strains of mice. We plan to probe the DNA with several kinds of cloned sequences. First, we will use identified cloned cDNA probes obtained from other laboratories. These have intrinsic interest as well as adding to the map. Second, we will use probes which we know hybridize to chromosomes which have very few polymorphic loci. These clones will be identified after hybridizing to DNA from a panel of mouse-hamster hybrid cell lines. They will be of two types. We will use random cDNA clones from libraries from a number of mouse organs. We also plan to use flanking regions to endogenous retroviruses which we will clone for genomic libraries of DNA from C57BL mouse strains. We have shown that these retroviruses occupy loci in C57BL which are not allelic to retroviral loci in other strains. This implies that they will hybridize to polymorphic DNA fragments. The fragment will contain a retrovirus in C57BL and will lack a retrovirus in other strains. As retroviruses appear to insert randomly in the mouse genome and mouse strains each have about 130 copies, they will be spaced about 12 cM apart on the mouse genome, and will be present on every chromosome. The achievement of a fully marked mouse map is essential to the full interpretation and analysis of regulatory genes, multigene phenotypes, and tumor susceptibility.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM028464-08
Application #
3275739
Study Section
Mammalian Genetics Study Section (MGN)
Project Start
1980-12-01
Project End
1991-08-31
Budget Start
1988-09-01
Budget End
1989-08-31
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Yen, C H; Pazik, J; Zhang, Y et al. (1997) An interstitial telomere array proximal to the distal telomere of mouse chromosome 13. Mamm Genome 8:411-7
Yen, C H; Hohman, C; Elliott, R W (1997) Mapping and characterization of three YAC clones containing TTAGGG arrays. Mamm Genome 8:775-7
Yen, C H; Pazik, J; Elliott, R W (1996) A polymorphic interstitial telomere array near the center of mouse chromosome 8. Mamm Genome 7:218-21
Yen, C H; Matsuda, Y; Chapman, V M et al. (1995) A genomic clone containing a telomere array maps near the centromere of mouse chromosome 6. Mamm Genome 6:96-102
McGinnis, J F; Lerious, V; Pazik, J et al. (1993) Chromosomal assignment of the recoverin gene and cancer-associated retinopathy. Mamm Genome 4:43-5
Adiletta, D C; Elliott, R W; Woodworth, M E (1993) Characterization of murine middle repetitive DNA. DNA Cell Biol 12:319-27
Ratty, A K; Matsuda, Y; Elliott, R W et al. (1992) Genetic mapping of two DNA markers, D16Ros1 and D16Ros2, flanking the mutation site in the chakragati mouse, a transgenic insertional mutant. Mamm Genome 3:5-10
Richards-Smith, B A; Brodeur, P H; Elliott, R W (1992) Deletion mapping of the mouse ornithine decarboxylase-related locus Odc-rs8 within Igh-V. Mamm Genome 3:568-74
Richards-Smith, B A; Elliott, R W (1992) Fine-structure mapping of the complex locus Odc-rs5 relative to Igk and distal loci. Mamm Genome 3:689-99
Richards-Smith, B A; Elliott, R W (1992) Mapping of the mouse ornithine decarboxylase-related sequence family. Mamm Genome 2:215-32

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