Construction of a yeast artificial chromosome contig encompassing the human acidic fibroblast growth factor (FGF1) gene: toward the cloning of the ANLL/MDS tumor-suppressor gene
| Autor: | Yang Liu, Ing-Ming Chiu, Robert A. Payson, Edward C. Gilmore |
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| Rok vydání: | 1994 |
| Předmět: |
Yeast artificial chromosome
Restriction Mapping Locus (genetics) Biology Hybrid Cells Chromosome Walking Gene mapping hemic and lymphatic diseases Cricetinae Genetics Animals Humans Genes Tumor Suppressor Cloning Molecular Gene Chromosomes Artificial Yeast Contig Base Sequence Chromosome Molecular biology Electrophoresis Gel Pulsed-Field Restriction enzyme Leukemia Myeloid Acute Genes Myelodysplastic Syndromes Cosmid Chromosomes Human Pair 5 Fibroblast Growth Factor 1 DNA Probes |
| Zdroj: | Genomics. 19(3) |
| ISSN: | 0888-7543 |
| Popis: | The region surrounding the human acidic fibroblast growth factor (FGF1) locus on chromosome 5q31 is of particular interest since it represents a critical region consistently lost in acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS) patients who have a demonstrable deletion of the distal portion of the long arm of chromosome 5. It is proposed that an ANLL/MDS leukemia suppressor gene resides on 5q31. We have previously shown that the gene is most likely localized between FGF1 and PDGFRB/CSF1R loci. The region has also been linked to at least four other genetic diseases, Treacher Collins syndrome, diastrophic dysplasia, limb-girdle muscular dystrophy, and an autosomal dominant deafness, by linkage analysis. Here, we describe yeast artificial chromosomes (YAC) spanning 450 kb around the FGF1 gene. Six YAC clones were isolated from a human YAC library and their restriction enzyme maps were determined. The overlap of the clones with each other and with FGF1 cosmid and phage clones was characterized. Three of the YAC clones were found to contain the entire FGF1 gene, which spans more than 100 kb. Proximal and distal ends of several of these YAC clones were isolated for further overlap cloning. The proximal ends of both Y2 and Y4 were localized to previously isolated FGF1 DNA by sequence analysis. The distal ends of these two clones also hybridized to a human-hamster hybrid containing chromosome 5 as the only human genetic material. These results suggest that these YAC clones represent colinear DNA around the FGF1 locus. None of the YAC clones were found to contain the CD14 and GRL genes, the closest known proximal and distal markers (relative to the centromere) to the FGF1 gene, respectively. This contig is useful for the overlap cloning of the 5q31 region and for reverse genetic strategies for the isolation of disease genes in the region. Moreover, the three YAC clones that contain the entire FGF1 gene in cloned forms can be introduced into transgenic mice to study the tissue-specific regulation of its four distinct promoters. |
| Databáze: | OpenAIRE |
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