A complete map for all human chromosomes would greatly facilitate understanding human biology and molecular disease. The studies proposed here will generate a restriction map of human chromosome 11 and align this map with the cytogenetic and genetic maps. Chromosome 11 was chosen since it encodes genes and has regions associated with diseases resulting from structural defects involved with oncogenes, growth factors, metabolic disorders, abnormal development, tumors, leukemias, chromosomal rearrangements and fragile sites. Another important reason for this study is the large number of cloned probes that have been mapped to this chromosome. It is clear that a very large number of ordered genetic markers are essential for accomplishing a complete map. Rather than employ only random DNA probes, we will isolate a unique set of ordered DNA clones for human chromosome 11 which are located at recognition sites for the rare cutting restriction enzymes NotI and SfiI. It is estimated that about 300 clones containing these recognition sites on chromosome 11 will be obtained, and will be sufficient to generate a complete chromosome 11 restriction map composed of overlapping DNA fragments 0.5 to 3 million base pairs in size. Probes will be isolated from a library of a Chinese hamster-human cell hybrid that retains chromosome 11 as its only chromosome. Positive human probes will be screened for the presence of rare cutter sites using labeled oligonucleotides for NotI and SfiI sequences. These sequences will be localized on chromosome 11 using our rapid mapping cell hybrid panel that will divide this chromosome into about tow dozen regions. Using pulsed field gel electrophoresis and these ordered markers, we will generate a restriction map for chromosome 11. The 140 random DNA markers that we have already mapped to regions of chromosome 11 and the more than 50 random probes we are currently isolating will be used to fill in and complete an ordered restriction map. Those probes recognizing restriction fragment polymorphisms will be employed in linkage maps to align the physical and genetic maps. Genes and abnormal chromosomal breakpoints associated with disease will be located on large restriction fragments which will precisely assign them on the physical map. This information will be significant for the molecular characterization of disease.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG000359-05
Application #
2208775
Study Section
Special Emphasis Panel (SRC)
Project Start
1988-09-28
Project End
1996-08-31
Budget Start
1992-09-30
Budget End
1996-08-31
Support Year
5
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Roswell Park Cancer Institute Corp
Department
Type
DUNS #
City
Buffalo
State
NY
Country
United States
Zip Code
14263
Schwartz, Jerrod J; Quake, Stephen R (2009) Single molecule measurement of the ""speed limit"" of DNA polymerase. Proc Natl Acad Sci U S A 106:20294-9
Zhang, J; Qin, S; Sait, S N et al. (2001) The pericentromeric region of human chromosome 11: evidence for a chromosome-specific duplication. Cytogenet Cell Genet 94:137-41
Reid, L H; Davies, C; Cooper, P R et al. (1997) A 1-Mb physical map and PAC contig of the imprinted domain in 11p15.5 that contains TAPA1 and the BWSCR1/WT2 region. Genomics 43:366-75
Qin, S; Nowak, N J; Zhang, J et al. (1996) A high-resolution physical map of human chromosome 11. Proc Natl Acad Sci U S A 93:3149-54
Wood, T F; Srivatsan, E S; Chakrabarti, R et al. (1996) A 1.5-megabase physical map encompassing the multiple endocrine neoplasia type-1 (MEN1) locus on chromosome 11q13. Genomics 38:166-73
Thate, C; Pongratz, J; Konig, A et al. (1995) CpG island clones for chromosome 11p--a resource for mapping and gene identification. Mamm Genome 6:421-5
Varanasi, R; Bardeesy, N; Ghahremani, M et al. (1994) Fine structure analysis of the WT1 gene in sporadic Wilms tumors. Proc Natl Acad Sci U S A 91:3554-8
Higgins, M J; Smilinich, N J; Sait, S et al. (1994) An ordered NotI fragment map of human chromosome band 11p15. Genomics 23:211-22
Rotman, G; Savitsky, K; Ziv, Y et al. (1994) A YAC contig spanning the ataxia-telangiectasia locus (groups A and C) at 11q22-q23. Genomics 24:234-42
Sait, S N; Nowak, N J; Singh-Kahlon, P et al. (1994) Localization of Beckwith-Wiedemann and rhabdoid tumor chromosome rearrangements to a defined interval in chromosome band 11p15.5. Genes Chromosomes Cancer 11:97-105

Showing the most recent 10 out of 15 publications