The goal of this proposal is to make a complete contig of mouse Chromosome 16 as YAC clones and to develop and sequence markers to provide an STS every 100 kb along the chromosome. The YACs will be developed so as to assure that these clones represent a long term resource for biological analysis as well as a transiently-useful mapping reagent. YACs will be developed from a mouse X human somatic cell hybrid, assuring a low chimera frequency (ca. 10%) and providing a useful human genomic YAC library as a by-product. YAC mapping and especially STS placement will be facilitated by the use of state of the art YAC vectors, yeast strains and methodologies that enlist yeast systems for genetic analysis as a """"""""silent partner"""""""" in the effort. In the first stage of this grant, a high resolution backcross panel consisting of 335 crossover points on Chr16 was developed. This map will permit efficient assignment, position and orientation of YACs and nascent contigs. The approach will take full advantage of the effort to generate 10,000 markers in the Genome Center at MIT, which will provide ca. 400 markers of Chr16 over the course of the project. Two hundred additional markers will be utilized. Up to 100 of these will derive from efforts of others to identify genes in evolutionarily conserved portions of human chromosomes. Within the project, several strategies will be used to analyze complex markers representing dozens of sequences on Chr16; markers from early embryonic stage-specific cDNA libraries representing genes that are inaccessible in human beings; random marker strategies; and markers from YACs of known positions in the CEPH/Genethon human chromosome 21 contig (and others as they become available). The final recombinational and physical maps will meet or exceed the five year goals for the mouse genome, will establish the most detailed comparative maps constructed to date, will provide considerable information about the positions of genes, and will derive a set of YACs as useful as any made to date for anticipated and unanticipated advances in genome analysis. This will be accomplished in a cost-competitive manner.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
2R01HG000405-07A1
Application #
2026806
Study Section
Genome Study Section (GNM)
Project Start
1991-04-01
Project End
2000-03-31
Budget Start
1997-04-01
Budget End
1998-03-31
Support Year
7
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Johns Hopkins University
Department
Physiology
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218
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Wiltshire, T; Pletcher, M; Cole, S E et al. (1999) Perfect conserved linkage across the entire mouse chromosome 10 region homologous to human chromosome 21. Genome Res 9:1214-22
Reeves, R H; Cabin, D E (1999) Mouse chromosome 16. Mamm Genome 10:957
Cole, S E; Wiltshire, T; Rue, E E et al. (1999) High-resolution comparative physical mapping of mouse chromosome 10 in the region of homology with human chromosome 21. Mamm Genome 10:229-34
Moore, C S; Lee, J S; Birren, B et al. (1999) Integration of cytogenetic with recombinational and physical maps of mouse chromosome 16. Genomics 59:1-5
Murakami, Y; Nobukuni, T; Tamura, K et al. (1998) Localization of tumor suppressor activity important in nonsmall cell lung carcinoma on chromosome 11q. Proc Natl Acad Sci U S A 95:8153-8
Borriello, F; Tizard, R; Rue, E et al. (1998) Characterization and localization of Mox2, the gene encoding the murine homolog of the rat MRC OX-2 membrane glycoprotein. Mamm Genome 9:114-8
Cole, S E; Wiltshire, T; Reeves, R H (1998) Physical mapping of the evolutionary boundary between human chromosomes 21 and 22 on mouse chromosome 10. Genomics 50:109-11
Cabin, D E; Reeves, R H (1998) Encyclopedia of the mouse genome VII. Mouse chromosome 16. Mamm Genome 8 Spec No:S307-19
Cole, S E; Reeves, R H (1998) A cluster of keratin-associated proteins on mouse chromosome 10 in the region of conserved linkage with human chromosome 21. Genomics 54:437-42

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