Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026986 (myelodysplastic syndrome)
 14,926 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID: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. 751 71

The q31-q33 region of chromosome 5 includes a number of genes encoding growth factors, growth factor receptors, and hormone/neurotransmitter receptors. The human fibroblast growth factor 1 locus (FGF1) resides in this region of chromosome 5, which is frequently lost in myelodysplastic syndromes and acute myeloid leukemia patients. Other disease loci, including the loci for limb-girdle muscular dystrophy and an autosomal dominant deafness, have been mapped on this region, but their genes have not been isolated. It was shown that the critical region lost in two patients with the 5q- syndrome resides between FGF1 and IL12B. We previously reported the construction of a yeast artificial chromosome (YAC) contig spanning 330 kb around the FGF1 gene. Here we report the isolation of additional YAC clones that extend 290 kb from the previous contig. Sequence-tagged sites developed from the outermost YAC ends were utilized in the contig cloning of two P1 clones P1Y2 and P1Y8. Together, these YAC and P1 clones span 720 kb around the FGF1 locus. With the use of fluorescence in situ hybridization, a physical map has been constructed of these P1 and GRL (glucocorticoid receptor locus) probes on metaphase and interphase chromosomes. On the basis of our work and the known orientation of GRL transcription, the determined order of these loci on chromosome 5q31.3-q32 is centromere-P1Y8-3'[FGF1]5'-P1Y2-5'[GRL]3'-telome re. Knowing the transcriptional orientation of the FGF1 gene relative to the centromere will now facilitate the directional cloning of clinically important genes that may reside in this region.
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PMID:Isolation of yeast artificial chromosomes containing the entire transcriptional unit of the human FGF1 gene: a 720-kb contig spanning human chromosome 5q31.3-->q32. 977 2

We have constructed a high-resolution map of a 6-Mb interval of human chromosome 5, band q31, incorporating 175 sequence tagged sites, of which 33 are genetic polymorphisms and 122 are nonredundant expressed sequences. The map was assembled initially as a YAC contig, incorporating data from radiation hybrid maps. To improve resolution and to identify errors in the databases, a radiation hybrid breakpoint map was developed for the interval, which included hybrids from both Stanford G3 and GeneBridge 4 panels. This novel approach facilitated the integration of one RH panel with another and enabled the identification and localization of new, previously unmapped ESTs from the radiation hybrid databases. ESTs were assembled into overlapping transcription units and ordered with respect to polymorphic markers in the region, resulting in a comprehensive map that incorporates markers from multiple different types of maps. This map of 5q31 will facilitate gene discovery efforts for several disorders, including limb-girdle muscular dystrophy type 1A and the genes deleted in acute myeloid leukemias and myelodysplasia. The study demonstrates the utility of a radiation hybrid breakpoint panel for correction of map errors and for the efficient identification of new transcript units in a large genomic interval.
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PMID:A radiation hybrid breakpoint map of the acute myeloid leukemia (AML) and limb-girdle muscular dystrophy 1A (LGMD1A) regions of chromosome 5q31 localizing 122 expressed sequences. 1019 Oct 80