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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 5q- syndrome is a myelodysplastic syndrome with specific hematological features and a good prognosis. Using molecular mapping techniques, we have previously defined the critical region of gene loss of the 5q- chromosome in the 5q- syndrome as the approximately 5-Mb region at 5q31-q33 flanked by the genes for FGF1 and IL12B. This region is completely represented by a series of overlapping YACs, and we are currently generating a transcription map with the aim of identifying the tumor-suppressor gene associated with the development of the 5q- syndrome. In this study two techniques have been used: first, the screening of full-length cDNA libraries with radiolabeled YACs and second, the mapping of chromosome 5-specific expressed sequence tags (ESTs) to a YAC contig. A 1-Mb YAC contig encompassing the CSF1R gene has been used to screen a fetal brain cDNA library, and this has resulted in the identification of two genes comprising one known gene previously localized to the region (ADRB2) and one known gene previously unlocalized. Six of 135 chromosome 5-specific ESTs were localized by PCR screening to the YAC contig mapping to the critical region of the 5q- syndrome. IMAGE cDNA clones for each of the six ESTs have been obtained. These seven (excluding ADRB2) newly assigned cDNA clones were subjected to further analysis. The expression patterns of each of the cDNA clones have been established in a range of human tissues, including bone marrow. Six of seven cDNAs are expressed in human bone marrow. Six of seven cDNAs have no known homology to any deposited human sequences, and one (C29) is dihydropyrimidinase-related protein-3, a member of a novel gene family. Genomic localization and expression patterns would suggest that these newly assigned cDNAs represent potential candidate genes for the 5q- syndrome.
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PMID:Novel genes mapping to the critical region of the 5q- syndrome. 933 64

The 5q- syndrome is a distinct type of myelodysplastic syndrome (MDS) characterised by refractory anaemia, morphological abnormalities of megakaryocytes, and del(5q) as the sole cytogenetic abnormality. In contrast to patients with therapy-related MDS with 5q deletions, 5q- syndrome patients have a favourable prognosis and a low rate of transformation to acute leukaemia. We have previously delineated a common deleted region of 5.6 Mb between the gene for fibroblast growth factor acidic (FGF1) and the subunit of interleukin 12 (IL12B) in two patients with 5q- syndrome and small deletions, del(5)(q31q33). The present study used fluorescence in situ hybridisation (FISH) analysis of these and a third 5q- syndrome patient with a small deletion, del(5)(q33q34), to refine further the critical deleted region. This resulted in the narrowing of the common deleted region within 5q31.3-5q33 to approximately 3 Mb, flanked by the adrenergic receptor beta 2 (ADRB2) and IL/2B genes. The common region of loss in these three 5q- syndrome patients includes the macrophage colony-stimulating factor-1 receptor (CSF1R), secreted protein, acidic, cysteine-rich (SPARC), and glutamate receptor (GR1A1) genes. This 5q- syndrome critical region is telomeric to and distinct from the other critical regions on 5q associated with MDS and acute myeloid leukaemia.
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PMID:Molecular cytogenetic delineation of the critical deleted region in the 5q- syndrome. 962 37