Abstract

The long term goal of this project to produce a battery of polymorphic markers for chromosome 3 which will serve as a framework for mapping and sequencing the chromosome. Currently, the chromosome 3 maps is sparse and only a handful of gene have been mapped to this large chromosome. Approximately 250 markers will be isolated for each chromosome and placed on radiation hybrid and linkage maps. The net result of this project will be a 2 cM map and physical markers approximately every megabase. The markers to be developed will be highly useful as they are highly polymorphic and PCR based. The first specific aim of the project is to produce highly polymorphic markers base on simple repeats. Repeats of 2, 3, and 4 base pairs will be isolated from chromosome specific libraries, and their sequence used to develop a PCR based assay.
A second aim i s to develop polymorphisms within known gene loci mapped to chromosome 3. The method of single strand conformational polymorphism (SSCP) and sequencing will identify polymorphism which will be detected in individuals by an allele specific oligonucleotide. Further markers will be developed in specific aim three for those regions of the chromosomes which lack markers. ALU PCR will be used on radiation reduced hybrids to generate region specific clones. These clones will be sequenced and analyzed for polymorphism. All the above mentioned markers will be placed on the physical map by radiation hybrids and the genetic map by analyzing CEPH and other family DNA. Because this project will generate PCR based polymorphisms, the markers will be immediately useful to the scientific community. Investigators seeking linkage markers will have a large reservoir of precisely mapped markers to draw upon. Our approach assimilates all the known data on chromosome 3 by incorporating known sequences into detailed physical and genetic maps. These markers are a first step towards a directed aligning of YAC and cosmid clones and will facilitate closure on this chromosome in the future.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Program Projects (P01)
Project #
5P01HG000470-05
Application #
5213028
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
5
Fiscal Year
1996
Total Cost
Indirect Cost

  Publications

Xiang, RuiHua; Davalos, Albert R; Hensel, Charles H et al. (2002) Semaphorin 3F gene from human 3p21.3 suppresses tumor formation in nude mice. Cancer Res 62:2637-43
Yu, K; Feingold, E (2001) Estimating the frequency distribution of crossovers during meiosis from recombination data. Biometrics 57:427-34
Hejna, J A; Timmers, C D; Reifsteck, C et al. (2000) Localization of the Fanconi anemia complementation group D gene to a 200-kb region on chromosome 3p25.3. Am J Hum Genet 66:1540-51
Wang, Z; Cody, J D; Leach, R J et al. (1999) Gene expression patterns in cell lines from patients with 18q- syndrome. Hum Genet 104:467-75
Maassen VanDenBrink, A; Vergouwe, M N; Ophoff, R A et al. (1998) Chromosomal localization of the 5-HT1F receptor gene: no evidence for involvement in response to sumatriptan in migraine patients. Am J Med Genet 77:415-20
Charlier, C; Singh, N A; Ryan, S G et al. (1998) A pore mutation in a novel KQT-like potassium channel gene in an idiopathic epilepsy family. Nat Genet 18:53-5
Trask, B J; Friedman, C; Martin-Gallardo, A et al. (1998) Members of the olfactory receptor gene family are contained in large blocks of DNA duplicated polymorphically near the ends of human chromosomes. Hum Mol Genet 7:13-26
Durkin, M E; Naylor, S L; Albrechtsen, R et al. (1997) Assignment of the gene for human tetranectin (TNA) to chromosome 3p22-->p21.3 by somatic cell hybrid mapping. Cytogenet Cell Genet 76:39-40
DuPont, B R; Garcia, D K; Sullivan, T M et al. (1997) Assignment of SAFB encoding Hsp27 ERE-TATA binding protein (HET)/scaffold attachment factor B (SAF-B) to human chromosome 19 band p13. Cytogenet Cell Genet 79:284-5
Kok, K; Naylor, S L; Buys, C H (1997) Deletions of the short arm of chromosome 3 in solid tumors and the search for suppressor genes. Adv Cancer Res 71:27-92

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